1.
Sharma, Aruna, et al.
(författare)
Topical application of CNTF, GDNF and BDNF in combination attenuates blood-spinal cord barrier permeability, edema formation, hemeoxygenase-2 upregulation, and cord pathology
2021
Ingår i: Brain protection strategies and nanomedicine. - : Elsevier BV. - 9780323989275 ; 266, s. 357-376
Bokkapitel (refereegranskat) abstract
Spinal cord injury (SCI) is one of the leading causes of disability in Military personnel for which no suitable therapeutic strategies are available till today. Thus, exploration of novel therapeutic measures is highly needed to enhance the quality of life of SCI victims. Previously, topical application of BDNF and GDNF in combination over the injured spinal cord after 90min induced marked neuroprotection. In present investigation, we added CNTF in combination with BDNF and/or GDNF treatment to examine weather the triple combination applied over the traumatic cord after 90 or 120min could thwart cord pathology. Since neurotrophins attenuate nitric oxide (NO) production in SCI, the role of carbon monoxide (CO) production that is similar to NO in inducing cell injury was explored using immunohistochemistry of the constitutive isoform of enzyme hemeoxygenase-2 (HO-2). SCI inflicted over the right dorsal horn of the T10-11 segments by making an incision of 2mm deep and 5mm long upregulated the HO-2 immunostaining in the T9 and T12 segments after 5h injury. These perifocal segments are associated with breakdown of the blood-spinal cord barrier (BSCB), edema development and cell injuries. Topical application of CNTF with BDNF and GDNF in combination (10ng each) after 90 and 120min over the injured spinal cord significantly attenuated the BSCB breakdown, edema formation, cell injury and overexpression of HO-2. These observations are the first to show that CNTF with BDNF and GDNF induced superior neuroprotection in SCI probably by downregulation of CO production, not reported earlier.
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4.
Sharma, Hari Shanker, et al.
(författare)
Preface
2020
Ingår i: Neuropharmacology of Neuroprotection. - : ELSEVIER. - 9780128208137 ; , s. XVII-XXIII
Bokkapitel (refereegranskat)
5.
Zhang, Zhiqiang, et al.
(författare)
Curcumin Suppresses Tumor Growth and Angiogenesis in Human Glioma Cells Through Modulation of Vascular Endothelial Growth Factor/Angiopoietin-2/Thrombospondin-1 Signaling
2017
Ingår i: CNS & Neurological Disorders. - : Bentham Science Publishers Ltd.. - 1871-5273 .- 1996-3181. ; 16:3, s. 346-350
Tidskriftsartikel (refereegranskat) abstract
Purpose: To investigate the effect of curcumin on tumor growth and angiogenesis of human gliomas and identify the underlying molecular mechanisms. Methods: A mouse xenograft glioma model was established by subcutaneously inoculating tumor cell aggregates derived from the U87 cell line. Mice were treated with 0.01ml/g body weight of curcumin or saline. Tumor volume was measured. Microvessel density was assessed by CD34 immunostaining, and angiogenesis by immunohistochemical staining of vascular endothelial growth factor (VEGF), angiopoietin-2 (Ang-2) and thrombospondin 1 (TSP-1). Results: At 28 days after treatment, tumor weights in the curcumin-treated group were much smaller than in the control group (0.23 +/- 0.11g vs. 0.44 +/- 0.15g p < 0.05), resulting in a 45.8% inhibition of tumor growth. Curcumin also markedly inhibited microvessel density. Expression of VEGF and Ang-2 was inhibited by curcumin, whereas TSP-1 expression was up-regulated. Conclusion: This study shows that curcumin inhibits tumor growth by inhibiting VEGF/Ang-2/TSP-1-mediated angiogenesis in a xenograft glioma mouse model.
6.
Chen, Huijing, et al.
(författare)
Application of olfactory ensheathing cells in clinical treatment of spinal cord injury : meta-analysis and prospect
2019
Ingår i: JOURNAL OF NEURORESTORATOLOGY. - 2324-2426. ; 7:2, s. 70-81
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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8.
Feng, Lianyuan, et al.
(författare)
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
Ingår i: Molecular Neurobiology. - : Humana Press. - 0893-7648 .- 1559-1182. ; 55:1, s. 350-358
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.
9.
Muresanu, Dafin Fior, et al.
(författare)
Hypertension Associated With Silica Dust Intoxication Aggravates Brain Pathology Following Traumatic Brain Injury : New Roles of Neurotrophic Factors
2017
Ingår i: The journal of head trauma rehabilitation. - 0885-9701 .- 1550-509X. ; 32:6, s. E68-E69
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.
10.
Muresanu, Dafin F., et al.
(författare)
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
Ingår i: Molecular Neurobiology. - : Springer Science and Business Media LLC. - 0893-7648 .- 1559-1182. ; 52:2, s. 837-845
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.
