| 1. |
- 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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| 2. |
- 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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| 3. |
- 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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| 4. |
- 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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| 5. |
- 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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| 6. |
- 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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| 7. |
- 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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| 8. |
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| 9. |
- 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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| 10. |
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