| 1. |
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| 2. |
- Biktimirov, Artur, et al.
(författare)
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Neuromodulation as a basic platform for neuroprotection and repair after spinal cord injury
- 2021
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Ingår i: Brain protection strategies and nanomedicine. - : Elsevier BV. - 9780323989275 ; , s. 269-300
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Bokkapitel (refereegranskat)abstract
- Spinal cord injury (SCI) is one of the most challenging medical issues. Spasticity is a major complication of SCI. A combination of spinal cord stimulation, new methods of neuroprotection and biomedical cellular products provides fundamentally new options for SCI treatment and rehabilitation. The paper attempts to critically analyze the effectiveness of using these procedures for patients with SCI, suggesting a protocol for a step-by-step personalized treatment of SCI, based on continuity of modern conservative and surgical methods. The study argues the possibility of using neuromodulation as a basis for rehabilitating patients with SCI.
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| 3. |
- Biktimirov, Artur, et al.
(författare)
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Spinal cord stimulation and intrathecal baclofen therapy for patients with severe spasticity after spinal cord injury
- 2020
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Ingår i: Neuropharmacology of Neuroprotection. - : ELSEVIER. - 9780128208137 ; , s. 79-99
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Bokkapitel (refereegranskat)abstract
- Rationale. Spasticity is one of the main complications after the spinal cord injury (SCI). Most commonly, severe cases of spasticity are treated surgically with intrathecal baclofen therapy (ITB). Spinal cord stimulation for chronic pains (SCS) serves as an alternative for ITB. Both methods have their benefits and limitations. This study is aimed at development of a personalized SCS and ITB treatment algorithm for patients with severe cases of spasticity after SCI. Materials and methods. The paper analyzes the treatment results of 66 patients with severe spasticity after SCI (50 men and 16 women, age ranging from 18 to 62), average age is 36.03 +/- 12.29 y.o. Patients who chose surgery as a spasticity treatment option, received experimental stimulation, and after muscle tone reduction to a comfort level they were surgically implanted with a SCS system for chronic pain management. Patients with negative response to experimental stimulation were tested for baclofen and, based on the results, had a baclofen pump implanted. The patients were examined after 1, 3, 6 and 12 months. Results. Surgical implantation of a SCS system was performed for 18 patients, ITB was used for 15 patients. After first 3 months of observation both groups demonstrated a significant improvement of spasticity index, but the SCS patients had better results. However, 6 months later the MAS scores, frequency of spasms and reflexes in both groups were the same. After 12 months of observation the ITB group exhibited a significant improvement of the MAS scores, compared with the control group, and reached the results, similar to the SCS group. Conclusions. Surgical treatment of patients with severe spasticity after SCI should start with experimental spinal cord stimulation, and, in case of a positive response, be followed by SCS system implantation. Patients with positive response to the experimental stimulation exhibit a significantly prolonged response to treatment, without substantial differences from ITB patients.
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| 4. |
- Bryukhovetskiy, Igor, et al.
(författare)
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Glioblastoma : What can we do for these patients today and what will we be able to do in the future?
- 2021
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Ingår i: NANOMEDICINE AND NEUROPROTECTION IN BRAIN DISEASES. - : ELSEVIER ACADEMIC PRESS INC. - 9780323901628 ; , s. 99-118
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Bokkapitel (refereegranskat)abstract
- Glioblastoma multiforme (GBM) is an extremely aggressive primary human brain tumor. The median survival of GBM patients is 15 months in case of completing the modern complex treatment protocol. Chemotherapy can help to extend the life expectancy of patients. GBM treatment resistance is associated with cancer stem cells (CSCs). The present paper analyses the main reasons for ineffectiveness of the existing GBM treatment methods and suggests treating CSCs as a complex phenomenon, resulting from the coordinated interaction of normal stem cells and cancer cells (CCs) in immunosuppressive microsurroundings. The GBM treatment strategy is suggested not for only suppressing strategically important signaling pathways in CCs, but also for regulating interaction between normal stem cells and cancer cells. The paper considers the issue of controlling penetrability of the blood-brain barrier that is one of the main challenges in neuro-oncology. Also, the paper suggests the ways of extending life expectancy of GBM patients today and prospects for the near future.
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| 5. |
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| 6. |
- Bryukhovetskiy, Igor, et al.
(författare)
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Personalized regulation of glioblastoma cancer stem cells based on biomedical technologies : From theory to experiment (Review)
- 2018
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Ingår i: International Journal of Molecular Medicine. - : SPANDIDOS PUBL LTD. - 1107-3756 .- 1791-244X. ; 42:2, s. 691-702
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Forskningsöversikt (refereegranskat)abstract
- Glioblastoma multiforme (GBM) is one of the most aggressive brain tumors. GBM represents >50% of primary tumors of the nervous system and similar to 20% of intracranial neoplasms. Standard treatment involves surgery, radiation and chemotherapy. However, the prognosis of GBM is usually poor, with a median survival of 15 months. Resistance of GBM to treatment can be explained by the presence of cancer stem cells (CSCs) among the GBM cell population. At present, there are no effective therapeutic strategies for the elimination of CSCs. The present review examined the nature of human GBM therapeutic resistance and attempted to systematize and put forward novel approaches for a personalized therapy of GBM that not only destroys tumor tissue, but also regulates cellular signaling and the morphogenetic properties of CSCs. The CSCs are considered to be an informationally accessible living system, and the CSC proteome should be used as a target for therapy directed at suppressing clonal selection mechanisms and CSC generation, destroying CSC hierarchy, and disrupting the interaction of CSCs with their microenvironment and extracellular matrix. These objectives can be achieved through the use of biomedical cellular products.
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| 7. |
- Bryukhovetskiy, Igor, et al.
(författare)
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Personalized therapy and stem cell transplantation for pro-inflammatory modulation of cancer stem cells microenvironment in glioblastoma : Review
- 2020
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Ingår i: NOVEL THERAPEUTIC ADVANCES IN GLIOBLASTOMA. - LONDON ENGLAND : Elsevier. - 9780128211144 ; , s. 67-98
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Bokkapitel (refereegranskat)abstract
- Glioblastoma multiforme (GBM) is one of the most aggressive types of brain tumor in humans. The prognosis for patients with GBM is unfavorable and treatment is largely ineffective, where modern treatment regimens typically increase survival by 15 months. GBM relapse and progression are associated with cancer stem cells (CSCs). The present review provides a critical analysis of the primary reasons underlying the lack of effectiveness of modern CSC management methods. An emphasis is placed on the role of the blood-brain barrier in the development of treatment resistance. The existing methods for increasing the efficiency of antitumor genotoxic therapy are also described, and a strategy for personalized regulation of CSC based on post-genome technologies is suggested. The hypothesis that GBM cells employ a special mechanism for DNA repair based on their interactions with normal stem cells, is presented and the function of the tumor microenvironment in fulfilling the antitumor potential of normal stem cells is explained. Additionally, the mechanisms by which cancer stem cells regulate glioblastoma progression and recurrence are described based on novel biomedical technologies.
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| 8. |
- Bryukhovetskiy, Igor, et al.
(författare)
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Transforming growth factor-beta mimics the key proteome properties of CD133- differentiated and CD133+ cancer stem cells in glioblastoma
- 2020
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Ingår i: Novel therapeutic advances in glioblastoma. - : Elsevier BV. - 9780128211144 ; , s. 219-242
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Bokkapitel (refereegranskat)abstract
- Glioblastoma multiforme is the most aggressive type of primary brain tumor in humans. Its invasive growth is associated with cluster of differentiation (CD)133 cancer stem cells (CSCs) and CD133(-) differentiated glioblastoma cells (DGCs) with aggressive phenotype, which are developed under the influence of transforming growth factor (TGF)-beta. The present study aimed to compare the proteomes of CD133 CSCs and CD133(-) DGCs stimulated by TGF-beta, as well as the expression levels of the main proteins responsible for activating the signaling pathway of receptor interactions with the extracellular matrix (ECM). The U87MG GBM cell line was used in this study. CSCs were extracted from gliomaspheres through magnetic-activated cell sorting based on the expression of CD133 (CD133); CD133(-) DCGs served as a control. CD133(-) DGCs of the U87-MG cell line were treated with 10ng/mL TGF-beta 1, and cell proliferation and migration were analyzed via real-time quantitative microscopy. High-performance liquid chromatography mass spectrometry was used for proteome analysis. The results revealed 589 proteins with significantly changes in expression among CD133 CSCs compared with those in CD133(-) DGCs (P < 0.05). Bioinformatics analysis allowed to attribute 134 differentially expressed proteins to 15 signaling pathways; among these proteins, 14 were involved in signaling cascades associated with the interaction between CSCs and the ECM, and were upregulated > twofold, while four proteins activated this signaling cascade. TGF-beta-stimulation increased the mobility, suppressed the proliferation and transformed the proteome profile of CD133(-) DGCs. Were identified 13 key proteins that activate the signaling pathway of receptor interaction with the ECM and three proteins activating this signaling pathway in CD133(-) DGCs which had the same values as those of CD133 CSCs. In conclusion, TGF-beta increased the expression of proteins that activate the signaling pathway of receptor interaction with the ECM in CD133(-) DGCs to the level of those in CD133 CSCs.
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| 9. |
- Chen, Huijing, et al.
(författare)
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Application of olfactory ensheathing cells in clinical treatment of spinal cord injury : meta-analysis and prospect
- 2019
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Ingår i: JOURNAL OF NEURORESTORATOLOGY. - 2324-2426. ; 7:2, s. 70-81
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Tidskriftsartikel (refereegranskat)abstract
- Background:A number of clinical trials of olfactory ensheathing cells (OECs) for the treatment of chronic spinal cord injury (SCI) have been carried out all over the world. However, their safety and efficacy have not been basically evaluated. Moreover, there are no uniform standards laid out for the use of optimal source, transplantation method and the dosage of OECs.Objective:This study evaluated the source, dose, and route of transplantation of OECs for the treatment of chronic SCI.Methods: PubMed, Cochrane Library, EMBASE, CNKI, and Wanfang Data were searched for the clinical studies of OECs in the treatment of chronic SCI on July 2018.Results:A total of 30 articles on OECs transplantation for chronic SCI were selected for comprehensive evaluation of OECs sources, doses, and transplantation methods. The efficacy of OECs in the treatment of chronic SCI was evaluated using Review Manager 5.3.Conclusion:Fetal OECs are the primary source of cells for the treatment of chronic SCI in OECs, with standardized cell-culture and quality-control processes. Fetal OECs can significantly improve the neurological function of patients with chronic SCI. It is an ideal cell therapy for neurorestoration. However to explore more precise and minimally invasive treatment options are required in the future.
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| 10. |
- Chen, Huijing, et al.
(författare)
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Multimodal imaging in the differential diagnosis of glioma recurrence from treatment-related effects : A protocol for systematic review and network meta-analysis
- 2021
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Ingår i: NANOMEDICINE AND NEUROPROTECTION IN BRAIN DISEASES. - : ELSEVIER ACADEMIC PRESS INC. - 9780323901628 ; , s. 377-383
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Bokkapitel (refereegranskat)abstract
- Background: Glioma is the most common malignant primary brain tumor and it will always recur. To date, various multimodal imaging including magnetic resonance imaging (MRI) and positron emission tomography computed tomography (PET/CT) was used to differentiate the diagnosis of true tumor recurrent (TuR) and treatment-related effects (TrE) in glioma patient but with no overall conclusion. In this study, SROC curve and Bayesian network meta-analysis will be used to conduct a comprehensive analysis of the results of different clinical reports, and assess the efficacy of multimodal imaging in difference TuR and TrE. Methods: To find more comprehensive information about the application of multimodal imaging in glioma patients, we searched the EMBASE, Pubmed, and Cochrane Central Register of Controlled Trials for relevant clinical trials. We also reviewed their reference lists to avoid omissions. QUADAS-2, RevMan software, Stata, and R software will be used. Results: This study will provide reliable evidence for the efficacy of multimodal imaging in the differential diagnosis of TuR and TrE in glioma patients. Conclusion: We will evaluate the effectiveness of different and rank each imaging method in glioma patients to provide a decision-making reference on which method to choose for clinicians.
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| 11. |
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| 12. |
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| 13. |
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| 14. |
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| 15. |
- Feng, Lianyuan, et al.
(författare)
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TiO2-Nanowired Delivery of DL-3-n-butylphthalide (DL-NBP) Attenuates Blood-Brain Barrier Disruption, Brain Edema Formation, and Neuronal Damages Following Concussive Head Injury
- 2018
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Ingår i: Molecular Neurobiology. - : Humana Press. - 0893-7648 .- 1559-1182. ; 55:1, s. 350-358
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Tidskriftsartikel (refereegranskat)abstract
- DL-3-n-butylphthalide (DL-NBP) is one of the constituents of Chinese celery extract that is used to treat stroke, dementia, and ischemic diseases. However, its role in traumatic brain injury is less well known. In this investigation, neuroprotective effects of DL-NBP in concussive head injury (CHI) on brain pathology were explored in a rat model. CHI was inflicted in anesthetized rats by dropping a weight of 114.6 g from a height of 20 cm through a guide tube on the exposed right parietal bone inducing an impact of 0.224 N and allowed them to survive 4 to 24 h after the primary insult. DL-NBP was administered (40 or 60 mg/kg, i.p.) 2 and 4 h after injury in 8-h survival group and 8 and 12 h after trauma in 24-h survival group. In addition, TiO2-nanowired delivery of DL-NBP (20 or 40 mg/kg, i.p.) in 8 and 24 h CHI rats was also examined. Untreated CHI showed a progressive increase in blood-brain barrier (BBB) breakdown to Evans blue albumin (EBA) and radioiodine (I[131]-), edema formation, and neuronal injuries. The magnitude and intensity of these pathological changes were most marked in the left hemisphere. Treatment with DL-NBP significantly reduced brain pathology in CHI following 8 to 12 h at 40-mg dose. However, 60-mg dose is needed to thwart brain pathology at 24 h following CHI. On the other hand, TiO2-DL-NBP was effective in reducing brain damage up to 8 or 12 h using a 20-mg dose and only 40-mg dose was needed for neuroprotection in CHI at 24 h. These observations are the first to suggest that (i) DL-NBP is quite effective in reducing brain pathology and (ii) nanodelivery of DL-NBP has far more superior effects in CHI, not reported earlier.
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| 16. |
- Lafuente, Jose Vicente, et al.
(författare)
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Diabetes Exacerbates Nanoparticles Induced Brain Pathology
- 2012
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Ingår i: CNS & Neurological Disorders. - : Bentham Science Publishers Ltd.. - 1871-5273 .- 1996-3181. ; 11:1, s. 26-39
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Forskningsöversikt (refereegranskat)abstract
- Long term exposure of nanoparticles e.g., silica dust (SiO2) from desert environments, or engineered nanoparticles from metals viz., Cu, Al or Ag from industry, ammunition, military equipment and related products may lead to adverse effects on mental health. However, it is unclear whether these nanoparticles may further adversely affect human health in cardiovascular or metabolic diseases e.g., hypertension or diabetes. It is quite likely that in diabetes or hypertension where the body immune system is already compromised there will be greater adverse effects following nanoparticles exposure on human health as compared to their exposure to healthy individuals. Previous experiments from our laboratory showed that diabetic or hypertensive animals are more susceptible to heat stress-induced neurotoxicity. Furthermore, traumatic injury to the spinal cord in SiO2 exposed rats resulted in exacerbation of cord pathology. However, whether nanoparticles such as Cu, Ag or SiO2 exposure will lead to enhanced neurotoxicity in diabetic animals are still not well investigated. Previous data from our laboratory showed that Cu or Ag intoxication (50 mg/kg, i.p. per day for 7 days) in streptozotocine induced diabetic rats exhibited enhanced neurotoxicity and exacerbation of sensory, motor and cognitive function as compared to normal animals under identical conditions. Thus the diabetic animals showed exacerbation of regional blood-brain barrier (BBB) disruption, edema formation and cell injuries along with greater reduction in the local cerebral blood flow (CBF) as compared to normal rats. These observations suggest that diabetic animals are more vulnerable to nanoparticles induced brain damage than healthy rats. The possible mechanisms and functional significance of these findings are discussed in this review largely based on our own investigations.
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| 17. |
- Li, Cong, et al.
(författare)
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Network pharmacological mechanism of Cinobufotalin against glioma
- 2021
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Ingår i: NANOMEDICINE AND NEUROPROTECTION IN BRAIN DISEASES. - : ELSEVIER ACADEMIC PRESS INC. - 9780323901628 ; , s. 119-137
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Bokkapitel (refereegranskat)abstract
- Objective: Cinobufotalin was extracted from the skin of Chinese giant salamander or black sable with good clinical effect against tumor. This study aims to explore the mechanism of Cinobufotalin components and predict the target of action of Cinobufotalin on glioma. Methods: The active components of Cinobufotalin were screened by the Chinese medicine pharmacology database and analysis platform (TCMSP), PubChem database, etc. The potential molecular components and targets were identified and enrichment analysis was conducted through the construction of related networks and analysis of their characteristics. Relevant targets of glioma were searched through TTD, DRUGBANK, and other databases, and the intersection was found and the key targets were found too. Results: A total of 21 active components and 184 target genes of Cinobufotalin were found. According to the enrichment analysis results, the pharmacological mechanism of Cinobufotalin mainly includes inhibition of the cell cycle, promotion of cell apoptosis, and regulation of immunity. On this basis, RAC1, FOS, and NOS3 can be preliminarily predicted as potential targets of Cinobufotalin in the treatment of glioma. Conclusions: The screening of active ingredients and target prediction based on network pharmacology can provide a new research idea for the multi-target treatment of glioma with Cinobufotalin.
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| 18. |
- Li, Cong, et al.
(författare)
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Targeted therapy with anlotinib for a leptomeningeal spread recurrent glioblastoma patient
- 2021
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Ingår i: NANOMEDICINE AND NEUROPROTECTION IN BRAIN DISEASES. - : ELSEVIER ACADEMIC PRESS INC. - 9780323901628 ; , s. 407-414
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Bokkapitel (refereegranskat)abstract
- Glioblastoma (GBM) is the most common and the most aggressive primary malignant brain tumor in adults. Although tumor recurrence is inevitable, leptomeningeal spread is relatively rare. We describe a case of leptomeningeal spread recurrent GBM treated with anlotinib in this report. When the recurrent GBM patient had leptomeningeal spread was administered anlotinib 10mg p.o. once every day and added oral temozolomide chemotherapy 100mg/m(2) (days 1-7, days 15-21, 28-day cycle) after 3 months. The patient's overall survival time was more than 5 months and developed oral ulcer and acute cerebral infarction during his oral administration of anlotinib. This patient showed a favorable clinic outcome for treatment of leptomeningeal spread recurrent GBM with anlotinib and didn't show serious side effects.
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| 19. |
- Li, Cong, et al.
(författare)
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The therapeutic and neuroprotective effects of an antiepileptic drug valproic acid in glioma patients
- 2020
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Ingår i: Neuropharmacology of Neuroprotection. - : ELSEVIER. - 9780128208137 ; , s. 369-379
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Bokkapitel (refereegranskat)abstract
- Glioma is the most common primary malignant brain tumor in adults and the patients have poor prognosis despite treatment with surgery, radiotherapy and chemotherapy. The anti-epileptic drug, valproic acid (VPA) as a HDAC inhibitors is often used in glioma patients even if the patients don't have brain tumors associated epilepsy (BAE). Some previous studies have found that VPA not only has anti-epileptic effect, but also has anti-glioma growth effect through enhance radiotherapy sensitivity or other mechanism. Then VPA is reported to improve the survival of glioma patients receiving chemoradiation therapy. In addition, there are limited researches have shown that VPA has a neuroprotective effect in protect normal cells and tissues from the deleterious effects of treatment of glioma, especially radiotherapy. We'll give a brief overview of these effects of VPA in glioma patients.
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| 20. |
- Lin, Jiuluan, et al.
(författare)
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Novel Method to Identify the Precentral Gyrus and Its Detailed Functional Distribution in Real Brain Surfaces Using Reconstructed 3D Brain Surface Imaging
- 2015
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Ingår i: JOURNAL OF MEDICAL IMAGING AND HEALTH INFORMATICS. - : American Scientific Publishers. - 2156-7018 .- 2156-7026. ; 5:2, s. 216-222
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To study the use of reconstructed 3D brain surface imaging (RBSI) to identify the precentral gyrus and its detailed functional distribution in epileptic patients. Method: A total of 12 refractory epilepsy cases that need intracranial electrode implantation were studied. In these patients, pre-operative magnetic resonance imaging (MRI) and functional MRI (fMRI) were conducted, and a cranial computed tomography (CT) scan was performed after electrode implantation. The RBSI was accomplished using Brain Voyager software based on MRI data, and then the 3D brain surface was integrated with the subdural electrode CT scan. The precentral gyrus was found in the reconstructed brain surface imaging according to their anatomical shape, and then were identified in the surgical field by comparing the exposed gyrus in the RBSI with the help of intraoperative photographs. Results: Total 12 cases of precentral gyrus was found and marked in the RBSI. There were 101 electrodes covering the precentral gyrus and 73 (72%) of them had motor response to electrical stimulation. In the contrast, (the area which is 1 cm ahead of the precentral gyrus), the motor response rate was 13% (17/130) (p < 0.05). During fMRI, 100% of the precentral gyrus and 58% (7/12) of post central gyrus was activated during hand movement. Whereas, no activation of the areas ahead of precentral gyrus was seen showing a significant difference between precentral gyrus and gyrus ahead. Conclusion: Our results demonstrated that using RBSI technique, it is possible to identify the precentral gyrus with precision.
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| 21. |
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| 22. |
- Lyakhova, Irina, et al.
(författare)
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3-Bromofascaplysin is a prospective chemical compound for developing new chemotherapy agents in glioblastoma treatment
- 2020
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Ingår i: Novel therapeutic advances in glioblastoma. - : Elsevier BV. - 9780128211144 ; , s. 325-343
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Bokkapitel (refereegranskat)abstract
- Glioblastoma (GB) is one of the most aggressive human brain tumors. The prognosis is unfavorable, its treatment is relatively ineffective, and the median survival is about 15months. Medication development with new chemical compounds is one of the ways to solve the problem of current treatment inefficiency. This study is focused on the group of chemical substances, based on pentacyclic system of 12H-pyrido[1,2-a:3,4-b] diindole, and the most well-known part of this group is fascaplysin, first extracted from the sponge Fascaplysinopsis spp. We have synthesized a series of the following fascaplysin derivatives: 7-phenylfascaplysin, 3-chlorofascaplysin, 3-bromofascaplysin, 9-bromofascaplysin. The paper is aimed at analyzing the cytotoxic effect of these compounds on GB cells. Materials and methods. The study used rat glioma C6 cell line (ATCC (R); cat no CCL-107), U-87MG cell line (ATCC; cat no. HTB-14T) and human glioblastoma T98-G cells (ATCC (R) CRL-1690T). Cell culture method, experimental pharmacological trials and.-radiation in vitro, as well as flow cytofluorometry were used in the study. Results: Cytotoxic effect of the tested compounds is stronger than the effect of unsubstituted fascaplysin, and appears to be dose-dependent and time-dependent. 3-bromofascaplysin is more efficient for cancer cells elimination, and by the end of the experiment the amount of living cancer cells in G(0) phase remained at its lowest. Cytotoxic effect of 3-bromofascaplysin on glioblastoma T98-G cells is inferior to that of TMZ, and in case of preliminary radiation treatment of cancer cells with 48Gy the effect of the compound matches the TMZ treatment results. Conclusion: 3-Bromofascaplysin is a prospective chemical compound for development of new anti-cancer chemotherapeutic agents.
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| 23. |
- Lyakhova, Irina, et al.
(författare)
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Alkaloids of fascaplysin are promising chemotherapeutic agents for the treatment of glioblastoma : Review
- 2020
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Ingår i: NOVEL THERAPEUTIC ADVANCES IN GLIOBLASTOMA. - LONDON ENGLAND : Elsevier. - 9780128211144 ; , s. 299-324
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Bokkapitel (refereegranskat)abstract
- Glioblastoma is one of the most aggressive human brain tumors. Even following all the modern protocols of complex treatment, the median patient survival typically does not exceed 15 months. This review analyzes the main reasons for glioblastoma resistance to therapy, as well as attempts at categorizing the main approaches to increasing chemotherapy efficiency. Special emphasis is placed on the specific group of compounds, known as marine alkaloids and their synthetic derivatives exerting a general antitumor effect on glioblastoma cells. The unique mechanisms of marine alkaloid influence on the tumor cells prompt considering them as a promising basis for creating new chemotherapeutic agents for glioblastoma treatment.
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| 24. |
- Menon, Preeti Kumaran, et al.
(författare)
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Cerebrolysin, a Mixture of Neurotrophic Factors Induces Marked Neuroprotection in Spinal Cord Injury Following Intoxication of Engineered Nanoparticles from Metals
- 2012
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Ingår i: CNS & Neurological Disorders - Drug Targets. - : Bentham Science Publishers Ltd.. - 1871-5273. ; 11:1, s. 40-49
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Forskningsöversikt (refereegranskat)abstract
- Spinal cord injury (SCI) is the world's most disastrous disease for which there is no effective treatment till today. Several studies suggest that nanoparticles could adversely influence the pathology of SCI and thereby alter the efficacy of many neuroprotective agents. Thus, there is an urgent need to find suitable therapeutic agents that could minimize cord pathology following trauma upon nanoparticle intoxication. Our laboratory has been engaged for the last 7 years in finding suitable therapeutic strategies that could equally reduce cord pathology in normal and in nanoparticle-treated animal models of SCI. We observed that engineered nanoparticles from metals e.g., aluminum (Al), silver (Ag) and copper (Cu) (50-60 nm) when administered in rats daily for 7 days (50 mg/kg, i.p.) resulted in exacerbation of cord pathology after trauma that correlated well with breakdown of the blood-spinal cord barrier (BSCB) to serum proteins. The entry of plasma proteins into the cord leads to edema formation and neuronal damage. Thus, future drugs should be designed in such a way to be effective even when the SCI is influenced by nanoparticles. Previous research suggests that a suitable combination of neurotrophic factors could induce marked neuroprotection in SCI in normal animals. Thus, we examined the effects of a new drug; cerebrolysin that is a mixture of different neurotrophic factors e.g., brain-derived neurotrophic factor (BDNF), glial cell line derived neurotrophic factor (GDNF), nerve growth factor (NGF), ciliary neurotrophic factor (CNTF) and other peptide fragments to treat normal or nanoparticle-treated rats after SCI. Our observations showed that cerebrolysin (2.5 ml/kg, i.v.) before SCI resulted in good neuroprotection in normal animals, whereas nanoparticle-treated rats required a higher dose of the drug (5.0 ml/kg, i.v.) to induce comparable neuroprotection in the cord after SCI. Cerebrolysin also reduced spinal cord water content, leakage of plasma proteins and the number of injured neurons. This indicates that cerebrolysin in higher doses could be a good candidate for treating SCI cases following nanoparticle intoxication. The possible mechanisms and functional significance of these findings are discussed in this review.
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| 25. |
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| 26. |
- Menon, Preeti K., et al.
(författare)
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Intravenous Administration of Functionalized Magnetic Iron Oxide Nanoparticles Does Not Induce CNS Injury in the Rat : Influence of Spinal Cord Trauma and Cerebrolysin Treatment
- 2017
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Ingår i: Nanomedicine In Central Nervous System Injury And Repair. - : Elsevier. - 9780128123812 ; , s. 47-63
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Bokkapitel (refereegranskat)abstract
- Influence of iron oxide magnetic nanoparticles (IOMNPs, 10nm in diameter, 0.25 or 0.50mg/mL in 100 mu L, i.v.) on the blood-brain barrier (BBB) permeability, edema formation, and neuronal or glial changes within 4-24h after administration was examined in normal rats and after a focal spinal cord injury (SCI). Furthermore, effect of cerebrolysin, a balanced composition of several neurotrophic factors, and active peptide fragments was also evaluated on IOMNP-induced changes in central nervous system (CNS) pathology. The SCI was inflicted in rats by making a longitudinal incision into the right dorsal horn of the T10-11 segments and allowed to survive 4 or 24h after trauma. Cerebrolysin (2.5 mL/kg, i.v.) was given either 30min before IOMNP injection in the 4-h SCI group or 4h after injury in the 24-h survival groups. Control group received cerebrolysin in identical situation following IOMNP administration. In all groups, leakage of serum albumin in the CNS as a marker of BBB breakdown and activation of astrocytes using glial fibrillary acidic protein was evaluated by immunohistochemistry. The neuronal injury was examined by Nissl staining. The IOMNPs alone in either low or high doses did not induce CNS pathology either following 4 or 24h after administration. However, administration of IOMNPs in SCI group slightly enhanced the pathological changes in the CNS after 24h but not 4h after trauma. Cerebrolysin treatment markedly attenuated IOMNP-induced aggravation of SCI-induced cord pathology and induced significant neuroprotection. These observations are the first to show that IOMNPs are safe for the CNS and cerebrolysin treatment prevented CNS pathology following a combination of trauma and IOMNP injection. This indicated that cerebrolysin might be used as adjunct therapy during IOMNP administration in disease conditions, not reported earlier.
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| 27. |
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| 28. |
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| 29. |
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| 30. |
- Muresanu, Dafin F., et al.
(författare)
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Diabetes aggravates heat stress-induced blood-brain barrier breakdown, reduction in cerebral blood flow, edema formation, and brain pathology : Possible neuroprotection with growth hormone
- 2010
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Ingår i: Annals of the New York Academy of Sciences. - : Wiley. - 0077-8923 .- 1749-6632. ; 1199, s. 15-26
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Tidskriftsartikel (refereegranskat)abstract
- The possibility that diabetes influences the outcome of heat stress-induced brain pathology was examined in our experimental rat model. Because growth hormone (GH) deficiency is an important factor in diabetes, the possible neuroprotective role of GH supplements was also examined in diabetic rats following heat stress. Rats receiving streptozotocine once daily for three days (50 mg/kg, i.p.) and allowed to survive four weeks resulted in diabetes (blood glucose level 18 and 20 mMol/L) compared to controls (blood glucose 4-6 mMol/L). Control or diabetic rats when subjected to four hours' heat stress at 38 degrees C in a biological oxygen demand incubator (BOD) showed profound disruption of the blood-brain barrier (BBB), reduction in cerebral blood flow (CBF), brain edema formation, and cell injury. These effects were most pronounced in diabetic rats. Pretreatment with GH (50 mu g/kg/min for 10 min before heat stress) significantly attenuated brain pathology in normal animals subjected to hyperthermia. On the other hand, almost a double dose of the growth hormone (80 to 120 mu g/g/min for 10 min) is needed in diabetic rats to induce considerable neuroprotection following heat stress. These observations are the first to suggest that diabetic rats are more vulnerable to heat stress-induced brain pathology and further show that the efficacy of neuroprotective drugs is also severely reduced in diabetic rats. Taken together, our results demonstrate that the dosage of neuroprotective drugs requires adjustment to enhance neuroprotection depending on the patient's endocrine or metabolic status, for example, diabetes mellitus, a finding not reported earlier.
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| 31. |
- Muresanu, Dafin F., et al.
(författare)
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Diabetes exacerbates brain pathology following a focal blast brain injury : New role of a multimodal drug cerebrolysin and nanomedicine
- 2020
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Ingår i: Neuropharmacology of Neuroprotection. - : ELSEVIER. - 9780128208137 ; 258, s. 285-367
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Bokkapitel (refereegranskat)abstract
- Blast brain injury (bBI) is a combination of several forces of pressure, rotation, penetration of sharp objects and chemical exposure causing laceration, perforation and tissue losses in the brain. The bBI is quite prevalent in military personnel during combat operations. However, no suitable therapeutic strategies are available so far to minimize bBI pathology. Combat stress induces profound cardiovascular and endocrine dysfunction leading to psychosomatic disorders including diabetes mellitus (DM). This is still unclear whether brain pathology in bBI could exacerbate in DM. In present review influence of DM on pathophysiology of bBI is discussed based on our own investigations. In addition, treatment with cerebrolysin (a multimodal drug comprising neurotrophic factors and active peptide fragments) or H-290/51 (a chain-breaking antioxidant) using nanowired delivery of for superior neuroprotection on brain pathology in bBI in DM is explored. Our observations are the first to show that pathophysiology of bBI is exacerbated in DM and TiO2-nanowired delivery of cerebrolysin induces profound neuroprotection in bBI in DM, not reported earlier. The clinical significance of our findings with regard to military medicine is discussed.
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| 32. |
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| 33. |
- Muresanu, Dafin Fior, et al.
(författare)
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Exacerbation of blood-brain barrier breakdown, edema formation, nitric oxide synthase upregulation and brain pathology after heat stroke in diabetic and hypertensive rats. Potential neuroprotection with cerebrolysin treatment
- 2019
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Ingår i: New Therapeutic Strategies for Brain Edema and Cell Injury. - : Elsevier. - 9780128167540 ; , s. 83-102
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Bokkapitel (refereegranskat)abstract
- There is a growing trend of hypertension among military and civilian populations due to lifetime stressful situations. If hypertension is uncontrolled it leads to development of diabetes and serious neurological complications. Most of the World populations live in temperate zone across the World. Thus, a possibility exists that these hypertensive and diabetic people may have external heat as potential risk factors for brain damage. We have seen brain edema and brain damage following exposure to heat stress at 38 degrees C for 4h. A possibility exists that heat exposure in diabetic-hypertensive (DBHY) cases exacerbates exacerbation of brain pathology and edema formation. This hypothesis is examined in a rat model. The role of nitric oxide (NO) in exacerbation of HS-induced brain pathology was also evaluated using nitric oxide synthase (NOS) immunoreactivity. Hypertensive rats (produced by two-kidney one clip (2K1C) method) were made diabetic with streptozotocine (50 mg/kg, i.p./day for 3 days) treatment. After 6 weeks, DBHY rats show 20-30 mM/L Blood Glucose and hypertension (180-200 mmHg). Subjection of these rats to 4h HS resulted in six- to eightfold higher BBB breakdown, brain edema formation and brain pathology. At this time, neuronal or inducible NOS expression was four- to sixfold higher in DBHY rats compared to controls. Interestingly, iNOS expression was higher than nNOS in DBHY rats. Cerebrolysin in high doses (10-mL/kg, i.v. instead of 5-mL/kg) induced significant neuroprotection and downregulation of nNOS and iNOS in DBHY animals whereas normal animals need only 5-mL/kg doses for this purpose. Our observations demonstrate that co-morbidly factors exacerbate brain damage in HS through NOS expression and require double dose of cerebrolysin for neuroprotection as compared to normal rats, not reported earlier.
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| 34. |
- Muresanu, Dafin Fior, et al.
(författare)
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Hypertension Associated With Silica Dust Intoxication Aggravates Brain Pathology Following Traumatic Brain Injury : New Roles of Neurotrophic Factors
- 2017
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Ingår i: The journal of head trauma rehabilitation. - 0885-9701 .- 1550-509X. ; 32:6, s. E68-E69
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Introduction/Rational: Military personnel engaged in combat operation are often exposed to desert storm resulting in silica dust (SiO2 nanoparticles) intoxication. In addition, combat stress, sleep deprivation and continuous attention for enemy group results in mild to moderate hypertension. Under such situations, any traumatic brain or spinal cord injury could result in massive brain pathology due to stress induced hypertension and possibly SiO2 nanoparticles intoxication. However, effects of trauma in hypertension and SiO2 intoxication are still not well known. In present study we investigated the effects of hypertension and SiO2 intoxication of the pathophysiology of traumatic brain injury (TBI).Method/Approach: Male Wistar rats (250-300 g) were made renal hypertensive by 2kidney 1clip (2K1C) procedure allowing mean arterial blood pressure (MABP) reaching 180 ± 8 torr over 6 weeks. These hypertensive rats were exposed to SiO2NPs (40-50 nm) once daily (50 mg/kg, i.p.) for 8 days. On the 9th day these hypertensive and SiO2NPs intoxicated animals were subjected to TBI under anesthesia by making an incision (3 mm long and 2.5 mm deep) on the right parietal cerebral cortex after opening the skull (4mmOD) on both sides. The animas were allowed to survive 48 h after TBI.Results/Effects: TBI in hypertensive and SiO2 nanoparticles intoxicated rats showed 4-to-6 fold higher breakdown of the blood-brain barrier (BBB) to Evans blue albumin (EBA) and [131]-Iodine, edema formation and neuronal injuries as compared to TBI in normal animals at 48 h. Treatment with a multimodal drug Cerebrolysin-containing balanced composition of neurotrophic factors and active peptide fragments (10 ml/kg, i.v.) started 4 h after TBI followed by 4 injections at every 8 h markedly reduced brain pathologies. Whereas only 5 ml/kg of the drug is needed to achieve identical neuroprotection in normal rats after TBI.Conclusions/Limitations: These observations are the first to show that a combination of hypertension and SiO2 nanoparticles worsens brain pathology in TBI. Under these situations almost double dose of drugs is needed to induce neuroprotection, not reported earlier. Our laboratory is engaged to see whether nanodelivery of cerebrolysin could have an added therapeutic value in this complicated situation of brain injury, a subject that is currently being investigated in our laboratory.
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| 35. |
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| 36. |
- Muresanu, Dafin F., et al.
(författare)
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Nanowired Delivery of Growth Hormone Attenuates Pathophysiology of Spinal Cord Injury and Enhances Insulin-Like Growth Factor-1 Concentration in the Plasma and the Spinal Cord
- 2015
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Ingår i: Molecular Neurobiology. - : Springer Science and Business Media LLC. - 0893-7648 .- 1559-1182. ; 52:2, s. 837-845
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Tidskriftsartikel (refereegranskat)abstract
- Previous studies from our laboratory showed that topical application of growth hormone (GH) induced neuroprotection 5 h after spinal cord injury (SCI) in a rat model. Since nanodelivery of drugs exerts superior neuroprotective effects, a possibility exists that nanodelivery of GH will induce long-term neuroprotection after a focal SCI. SCI induces GH deficiency that is coupled with insulin-like growth factor-1 (IGF-1) reduction in the plasma. Thus, an exogenous supplement of GH in SCI may enhance the IGF-1 levels in the cord and induce neuroprotection. In the present investigation, we delivered TiO2-nanowired growth hormone (NWGH) after a longitudinal incision of the right dorsal horn at the T10-11 segments in anesthetized rats and compared the results with normal GH therapy on IGF-1 and GH contents in the plasma and in the cord in relation to blood-spinal cord barrier (BSCB) disruption, edema formation, and neuronal injuries. Our results showed a progressive decline in IGF-1 and GH contents in the plasma and the T9 and T12 segments of the cord 12 and 24 h after SCI. Marked increase in the BSCB breakdown, as revealed by extravasation of Evans blue and radioiodine, was seen at these time points after SCI in association with edema and neuronal injuries. Administration of NWGH markedly enhanced the IGF-1 levels and GH contents in plasma and cord after SCI, whereas normal GH was unable to enhance IGF-1 or GH levels 12 or 24 h after SCI. Interestingly, NWGH was also able to reduce BSCB disruption, edema formation, and neuronal injuries after trauma. On the other hand, normal GH was ineffective on these parameters at all time points examined. Taken together, our results are the first to demonstrate that NWGH is quite effective in enhancing IGF-1 and GH levels in the cord and plasma that may be crucial in reducing pathophysiology of SCI.
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| 37. |
- Muresanu, Dafin F., et al.
(författare)
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Nanowired Drug Delivery of Antioxidant Compound H-290/51 Enhances Neuroprotection in Hyperthermia-Induced Neurotoxicity
- 2012
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Ingår i: CNS & Neurological Disorders. - : Bentham Science Publishers Ltd.. - 1871-5273 .- 1996-3181. ; 11:1, s. 50-64
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Forskningsöversikt (refereegranskat)abstract
- Nanoparticles from the environment or through industrial sources can induce profound alterations in human health, often leading to brain dysfunction. However, it is still unclear whether nanoparticle intoxication could also alter the physiological or pathological responses of additional brain injury, stress response or disease processes. Military personals engaged in combat or peacekeeping operations are often exposed to nanoparticles from various environmental sources, e.g., Ag, Cu, Si, C, Al. In addition, these military personals are often exposed to high environmental heat, or gun and missle explosion injury leading to head or spinal trauma. Thus it is likely that additional CNS injury or stress-induced pathophysiological processes are influenced by nanoparticle intoxication. In this situation, when a combination of nanoparticles and central nervous system (CNS) injury or stress exist together, drug therapy needed to correct these anomalies may not work as effectively as in normal situation. Previous studies from our laboratory show that nanoparticle-intoxicated animals when subjected to hyperthermia resulted in exacerbation of brain pathology. In these animals, antioxidant compounds, e.g., H-290/51 that inhibits free radical formation and induces marked neuroprotection in normal rats after heat stress, failed to protect brain damage when a combination of nanoparticles and heat exposure was used. However, nanowired H-290/51 resulted in better neuroprotection in nanoparticles intoxicated animals after heat stress. Interestingly, high doses of the normal compound induced some neuroprotection in these nanoparticle-treated, heat-stressed rats. These observations suggest that a combination of nanoparticles and heat stress is dangerous and in such situations modification of drug dosage is needed to achieve comparable neuroprotection. In this review possible mechanisms of nanoparticle-induced exacerbation of heat induced neurotoxicity and brain protection achieved by nanowired drug delivery is discussed that is largely based on our own investigations.
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| 38. |
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| 39. |
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| 40. |
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| 41. |
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| 42. |
- Niu, Feng, et al.
(författare)
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Co-administration of TiO2-nanowired DL-3-n-butylphthalide (DL-NBP) and mesenchymal stem cells enhanced neuroprotection in Parkinson's disease exacerbated by concussive head injury
- 2020
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Ingår i: Neuropharmacology of Neuroprotection. - : ELSEVIER. - 9780128208137 ; , s. 101-155
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Bokkapitel (refereegranskat)abstract
- DL-3-n-butylphthalide (DL-NBP) is a powerful antioxidant compound with profound neuroprotective effects in stroke and brain injury. However, its role in Parkinson's disease (PD) is not well known. Traumatic brain injury (TBI) is one of the key factors in precipitating PD like symptoms in civilians and particularly in military personnel. Thus, it would be interesting to explore the possible neuroprotective effects of NBP in PD following concussive head injury (CHI). In this chapter effect of nanowired delivery of NBP together with mesenchymal stem cells (MSCs) in PD with CHI is discussed based on our own investigations. It appears that CHI exacerbates PD pathophysiology in terms of p-tau, alpha-synuclein (ASNC) levels in the cerebrospinal fluid (CSF) and the loss of TH immunoreactivity in substantia niagra pars compacta (SNpc) and striatum (STr) along with dopamine (DA), dopamine decarboxylase (DOPAC). And homovanillic acid (HVA). Our observations are the first to show that a combination of NBP with MSCs when delivered using nanowired technology induces superior neuroprotective effects in PD brain pathology exacerbated by CHI, not reported earlier.
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| 43. |
- Niu, Feng, et al.
(författare)
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Nanodelivery of oxiracetam enhances memory, functional recovery and induces neuroprotection following concussive head injury
- 2021
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Ingår i: Progress in Brain Research. - Amsterdam : Elsevier. - 0079-6123 .- 1875-7855. ; 265, s. 139-230, s. 139-230
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Tidskriftsartikel (refereegranskat)abstract
- Military personnel are the most susceptible to concussive head injury (CHI) caused by explosion, blast or missile or blunt head trauma. Mild to moderate CHI could induce lifetime functional and cognitive disturbances causing significant decrease in quality of life. Severe CHI leads to instant death and lifetime paralysis. Thus, further exploration of novel therapeutic agents or new features of known pharmacological agents are needed to enhance quality of life of CHI victims.Previous reports from our laboratory showed that mild CHI induced by weight drop technique causing an impact of 0.224 N results in profound progressive functional deficit, memory impairment and brain pathology from 5 h after trauma that continued over several weeks of injury.In this investigation we report that TiO2 nanowired delivery of oxiracetam (50 mg/kg, i.p.) daily for 5 days after CHI resulted in significant improvement of functional deficit on the 8th day. This was observed using Rota Rod treadmill, memory improvement assessed by the time spent in finding hidden platform under water. The motor function improvement is seen in oxiracetam treated CHI group by placing forepaw on an inclined mesh walking and foot print analysis for stride length and distance between hind feet. TiO2-nanowired oxiracetam also induced marked improvements in the cerebral blood flow, reduction in the BBB breakdown and edema formation as well as neuroprotection of neuronal, glial and myelin damages caused by CHI at light and electron microscopy on the 7th day after 5 days TiO2 oxiracetam treatment. Adverse biochemical events such as upregulation of CSF nitrite and nitrate, IL-6, TNF-a and p-Tau are also reduced significantly in oxiracetam treated CHI group. On the other hand post treatment of 100 mg/kg dose of normal oxiracetam in identical conditions after CHI is needed to show slight but significant neuroprotection together with mild recovery of memory function and functional deficits on the 8th day. These observations are the first to point out that nanowired delivery of oxiracetam has superior neuroprotective ability in CHI. These results indicate a promising clinical future of TiO2 oxiracetam in treating CHI patients for better quality of life and neurorehabilitation, not reported earlier.
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| 44. |
- Niu, Feng, et al.
(författare)
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Nanowired delivery of DL-3-n-butylphthalide induces superior neuroprotection in concussive head injury
- 2019
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Ingår i: NANONEUROPROTECTION AND NANONEUROTOXICOLOGY. - : ACADEMIC PRESS LTD-ELSEVIER SCIENCE LTD. - 9780444642080 ; , s. 89-118
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Bokkapitel (refereegranskat)abstract
- Concussive head injury (CHI) is quite prevalent in military personnel leading to lifetime disability in more than 85% of cases. Other reasons of CHI include motor vehicle accident, fall or blunt trauma under various conditions. In United States of America (USA) alone more than 150k cases of head injury are added every year for which no suitable therapeutic strategies are still available. Thus, there is a need to expand our knowledge in treating CHI cases with novel therapeutic measures to enhance the quality of life of head injury victims. With recent advancements in nanodelivery of drugs for superior neuroprotective effects in neurological diseases, our laboratory is engaged in understanding the role of nanowired delivery of suitable drugs in treating CHI and other neurodegenerative diseases. DL-3-n-butylphthalide (NBP) is an extract of Chinese celery and is able to induce profound neuroprotection following ischemic stroke and other related neurological dysfunction. Thus, it is quite likely that synthetic NBP could have pronounced neuroprotective effects in CHI as well. We believe that nanodelivery of NBP have superior neuroprotection in CHI. In this review neuroprotective effects of nanowired delivery of NBP in CHI induced brain pathology is described. Our experimental observations show that nanowired delivery of NBP results in superior neuroprotection than the regular NBP in CHI. The probable mechanisms and functional significance of our finding in relation to military medicine is discussed based on our own investigations.
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| 45. |
- Ozkizilcik, Asya, et al.
(författare)
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Nanodelivery of cerebrolysin reduces pathophysiology of Parkinson's disease
- 2019
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Ingår i: NANONEUROPROTECTION AND NANONEUROTOXICOLOGY. - : ACADEMIC PRESS LTD-ELSEVIER SCIENCE LTD. - 9780444642080 ; , s. 201-246
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Bokkapitel (refereegranskat)abstract
- Parkinson's disease (PD) is affecting >10 million people worldwide for which no suitable cure has been developed so far. Roughly, about two people per thousand populations are affected with PD like symptoms especially over the age of 50. About 1% of the populations above 60 years suffer from PD-like disease. The prevalence of the disease is increasing over the years, and future projections by 2020 could be 12-14 millions people affected by the disease. Thus, exploration of suitable therapeutic measures is the need of the hour to enhance quality of the life of PD patients. PD induced brain pathology includes loss of dopaminergic neurons in the substantia niagra that could later extends to other cortical regions causing loss of voluntary motor control. Deposition of alpha-synuclein in the brain further leads to neurodegeneration. However, the exact cause of PD is still unknown. It appears that breakdown of the blood-brain barrier (BBB) and leakage of serum component into the brain could lead to neurodegeneration in PD. Thus, novel treatment strategies that are able to restore BBB breakdown and enhance neuronal plasticity and neuroregeneration in PD could be effective in future therapy. With the advancement of nanotechnology, it is worthwhile to understand the role of nanodelivery of selected agents in PD to enhance neuroprotection. In this review new role of BBB, brain edema, and neuropathology in PD is discussed. In addition, superior neuroprotection induced by nanowired delivery of a multimodal drug cerebrolysin in PD is summarized based on our own investigations.
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| 46. |
- Ozkizilcik, Asya, et al.
(författare)
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Timed Release of Cerebrolysin Using Drug-Loaded Titanate Nanospheres Reduces Brain Pathology and Improves Behavioral Functions in Parkinson's Disease
- 2018
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Ingår i: Molecular Neurobiology. - : HUMANA PRESS INC. - 0893-7648 .- 1559-1182. ; 55:1, s. 359-369
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Tidskriftsartikel (refereegranskat)abstract
- Previous studies from our laboratory show that intraperitoneal injections of 1-metyl-4-phenyl-1,2,3,6-tetrahydropyridin (MPTP, 20 mg/kg) daily within 2-h intervals for 5 days in mice induce Parkinson's disease (PD)-like symptoms on the 8th day. A significant decrease in dopamine (DA) and its metabolites 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) along with a marked decrease in the number of tyrosine hydroxylase (TH)-positive cells in the substantia nigra pars compacta (SNpc) and striatum (STr) confirms the validity of this model for studying PD. Since cerebrolysin (CBL) is a well-balanced composition of several neurotrophic factors and active peptide fragments, in the present investigation we examined the timed release of CBL using titanate nanospheres (TiNS) in treating PD in our mouse model. Our observations show that TiNS-CBL (in a dose of 3 ml/kg, i.v.) given after 2 days of MPTP administration for 5 days resulted in a marked increase in TH-positive cells in the SNpc and STr as compared to normal CBL. Also, TiNS-CBL resulted in significantly higher levels of DA, DOPAC, and HVA in SNpc and STr on the 8th day as compared to normal CBL therapy. TiNS-CBL also thwarted increased alpha-synuclein levels in the brain and in the cerebrospinal fluid (CSF) as well as neuronal nitric oxide synthase (nNOS) in the in PD brain as compared to untreated group. Behavioral function was also significantly improved in MPTP-treated animals that received TiNS-CBL. These observations are the first to demonstrate that timed release of TiNS-CBL has far more superior neuroprotective effects in PD than normal CBL.
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| 47. |
- Pak, Oleg, et al.
(författare)
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Effectiveness of bortezomib and temozolomide for eradication of recurrent human glioblastoma cells, resistant to radiation
- 2021
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Ingår i: Brain protection strategies and nanomedicine. - : Elsevier BV. - 9780323989275 ; , s. 195-209
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Bokkapitel (refereegranskat)abstract
- Background: Glioblastoma multiforme (GBM) is a primary human brain tumor with the highest mortality rate. The prognosis for such patients is unfavorable, since the tumor is highly resistant to treatment, and the median survival of patients is 13 months. Chemotherapy might extend patients' life, but a tumor, that reappears after chemoradiotherapy, is resistant to temozolomide (TMZ). Using postgenome technologies in clinical practice might have a positive effect on the treatment of a recurrent GBM.Methods: T98G cells of human GBM have been used. Radiation treatment was performed with Rokus-M gamma-therapeutic system, using Co-60 as a source of radionuclide emissions. High-performance liquid chromatography-mass spectrometry was used for proteome analysis. Mass spectrometry data were processed with MaxQuant (version 1.6.1.0) and Perseus (version 1.6.1) software, Max Planck Institute of Biochemistry (Germany). Biological processes, molecular functions, cells locations and protein pathways were annotated with a help of PubMed, PANTHER, Gene Ontology and KEGG and STRING v10 databases. Pharmaceutical testing was performed in vitro with a panel of traditional chemotherapeutic agents.Results: GBM cells proliferation speed is inversely proportional to the irradiation dose and recedes when the dosage is increased, as expected. Synthesis of ERC1, NARG1L, PLCD3, ROCK2, SARNP, TMSB4X and YTHDF2 in GBM cells, treated with 60Gy of radiation, shows more than a fourfold increase, while the synthesis level of PSMA2, PSMA3, PSMA4, PSMB2, PSMB3, PSMB7, PSMC3, PSMD1, PSMD3 proteins increases significantly. Traditional chemotherapeutic agents are not very effective against cancer cells of the recurrent GBM. Combination of TMZ and CCNU with a proteasome inhibitor-bortezomib-significantly increases their ability to eradicate cells of a radioresistant GBM.Conclusions: Bortezomib and temozolomide effectively destroy cells of a radioresistant recurrent human glioblastoma; proteome mapping of the recurrent GBM cancer cells allows to identify new targets for therapy to improve the treatment results.
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| 48. |
- Pandey, Anand Kumar, et al.
(författare)
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Quercetin in hypoxia-induced oxidative stress : novel target for neuroprotection
- 2012
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Ingår i: New Perspectives of Central Nervous System Injury and Neuroprotection. - : Elsevier. - 9780123869869 ; , s. 107-146
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Bokkapitel (refereegranskat)abstract
- Oxidative stress in the central nervous system is one of the key players for neurodegeneration. Thus, antioxidants could play important roles in treating several neurodegenerative diseases including Alzheimer's disease, Parkinson's disease, and aging-related brain disorders. This review is focused on the new developments in oxidative stress-induced neurodegeneration. Further, based on our own investigations, new roles of quercetin, an antioxidant compound in hypoxia and ischemia induced neuroprotection in relation to suppression of oxidative stress, improvement in behavioral function, reduction in infarct volume, brain swelling, and cellular injury in both in vivo and in vitro models are discussed. Our new findings clearly suggest that antioxidant compounds have potential role in therapeutic strategies to treat neurodegenerative diseases in clinical settings.
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| 49. |
- Patnaik, Ranjana, et al.
(författare)
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Histamine H3 Inverse Agonist BF 2649 or Antagonist with Partial H4 Agonist Activity Clobenpropit Reduces Amyloid Beta Peptide-Induced Brain Pathology in Alzheimer's Disease
- 2018
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Ingår i: Molecular Neurobiology. - : Humana Press. - 0893-7648 .- 1559-1182. ; 55:1, s. 312-321
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Tidskriftsartikel (refereegranskat)abstract
- Alzheimer's disease (AD) is one of the leading causes for disability and death affecting millions of people worldwide. Thus, novel therapeutic strategies are needed to reduce brain pathology associated with AD. In view of increasing awareness regarding involvement of histaminergic pathways in AD, we explored the role of one H3 receptor inverse agonist BF 2649 and one selective H3 receptor antagonist with partial H4 agonist activity in amyloid beta peptide (A beta P) infusion-induced brain pathology in a rat model. AD-like pathology was produced by administering A beta P (1-40) intracerebroventricular (i.c.v.) in the left lateral ventricle (250 ng/10 mu l, once daily) for 4 weeks. Control rats received saline. In separate group of rats, either BF 2649 (1 mg/kg, i.p.) or clobenpropit (1 mg/kg, i.p.) was administered once daily for 1 week after 3weeks of A beta P administration. After 30 days, blood-brain barrier (BBB) breakdown, edema formation, neuronal, glial injuries, and A beta P deposits were examined in the brain. A significant reduction in A beta P deposits along with marked reduction in neuronal or glial reactions was seen in the drug-treated group. The BBB breakdown to Evans blue albumin and radioiodine in the cortex, hippocampus, hypothalamus, and cerebellum was also significantly reduced in these drug-treated groups. Clobenpropit showed superior effects than the BF2649 in reducing brain pathology in AD. Taken together, our observations are the first to show that blockade of H3 and stimulation of H4 receptors are beneficial for the treatment of AD pathology, not reported earlier.
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| 50. |
- Qu, Suqing, et al.
(författare)
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Clinical Observation of Electroencephalographic Changes and Risk of Convulsion Occurrence in Children Receiving Neural Precursor Cell Transplantation
- 2018
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Ingår i: CNS & Neurological Disorders. - : Bentham Science Publishers Ltd.. - 1871-5273 .- 1996-3181. ; 17:3, s. 233-239
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: This study was intended to observe electroencephalographic (EEG) changes and convulsion attacks in children receiving neural precursor cell transplantation, and to explore the possibility of electrophysiological changes and risk of convulsion occurrence after cell transplantation.Method: 228 children were included in this study who received neural precursor cell transplantation in our hospital between March 2008 and July 2012. No history of convulsion attacks was elicited before cell transplantation. Data about EEG change and convulsion occurrence before and after cell transplantation were analyzed statistically.Results: Of the 228 pediatric patients, EEG improvement, deterioration and no significant change were observed in 60, 45 and 122 patients, respectively. One month after transplantation, four (1.76%) patients experienced new convulsions. Of the 227 patients, 25 showed increased and/or abnormal discharges on EEG. Of these, 19 underwent EEG re-examination six months post-operation. Except the convulsive cases mentioned above, there were no new cases of convulsions in the remaining patients. Of the 27 patients including those with abnormal discharge, increased discharge and convulsion attacks, 17 achieved varying degrees of therapeutic efficacy.Conclusion: Intraventricular transplantation of neural precursor cells is associated with EEG changes in some children and clinical convulsion attacks in individual patients. However, these abnormal changes do not last long and usually return to normal levels within 1-6 months after surgery, along with disappearance of convulsions. Simultaneous occurrence of EEG changes and convulsions do not appear to affect therapeutic efficacy.
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