scholarly journals Neuroprotective Role of Hypothermia in Acute Spinal Cord Injury

Biomedicines ◽  
2022 ◽  
Vol 10 (1) ◽  
pp. 104
Author(s):  
Hasan Al-Nashash ◽  
Angelo H. ALL

Even nowadays, the question of whether hypothermia can genuinely be considered therapeutic care for patients with traumatic spinal cord injury (SCI) remains unanswered. Although the mechanisms of hypothermia action are yet to be fully explored, early hypothermia for patients suffering from acute SCI has already been implemented in clinical settings. This article discusses measures for inducing various forms of hypothermia and summarizes several hypotheses describing the likelihood of hypothermia mechanisms of action. We present our objective neuro-electrophysiological results and demonstrate that early hypothermia manifests neuroprotective effects mainly during the first- and second-month post-SCI, depending on the severity of the injury, time of intervening, duration, degree, and modality of inducing hypothermia. Nevertheless, eventually, its beneficial effects gradually but consistently diminish. In addition, we report potential complications and side effects for the administration of general hypothermia with a unique referment to the local hypothermia. We also provide evidence that instead of considering early hypothermia post-SCI a therapeutic approach, it is more a neuroprotective strategy in acute and sub-acute phases of SCI that mostly delay, but not entirely avoid, the natural history of the pathophysiological events. Indeed, the most crucial rationale for inducing early hypothermia is to halt these devastating inflammatory and apoptotic events as early and as much as possible. This, in turn, creates a larger time-window of opportunity for physicians to formulate and administer a well-designed personalized treatment for patients suffering from acute traumatic SCI.

Polymers ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 2245
Author(s):  
Jue-Zong Yeh ◽  
Ding-Han Wang ◽  
Juin-Hong Cherng ◽  
Yi-Wen Wang ◽  
Gang-Yi Fan ◽  
...  

In spinal cord injury (SCI) therapy, glial scarring formed by activated astrocytes is a primary problem that needs to be solved to enhance axonal regeneration. In this study, we developed and used a collagen scaffold for glial scar replacement to create an appropriate environment in an SCI rat model and determined whether neural plasticity can be manipulated using this approach. We used four experimental groups, as follows: SCI-collagen scaffold, SCI control, normal spinal cord-collagen scaffold, and normal control. The collagen scaffold showed excellent in vitro and in vivo biocompatibility. Immunofluorescence staining revealed increased expression of neurofilament and fibronectin and reduced expression of glial fibrillary acidic protein and anti-chondroitin sulfate in the collagen scaffold-treated SCI rats at 1 and 4 weeks post-implantation compared with that in untreated SCI control. This indicates that the collagen scaffold implantation promoted neuronal survival and axonal growth within the injured site and prevented glial scar formation by controlling astrocyte production for their normal functioning. Our study highlights the feasibility of using the collagen scaffold in SCI repair. The collagen scaffold was found to exert beneficial effects on neuronal activity and may help in manipulating synaptic plasticity, implying its great potential for clinical application in SCI.


Author(s):  
Hao Zhang ◽  
Alexander Younsi ◽  
Guoli Zheng ◽  
Mohamed Tail ◽  
Anna-Kathrin Harms ◽  
...  

Abstract Purpose The Sonic Hedgehog (Shh) pathway has been associated with a protective role after injury to the central nervous system (CNS). We, therefore, investigated the effects of intrathecal Shh-administration in the subacute phase after thoracic spinal cord injury (SCI) on secondary injury processes in rats. Methods Twenty-one Wistar rats were subjected to thoracic clip-contusion/compression SCI at T9. Animals were randomized into three treatment groups (Shh, Vehicle, Sham). Seven days after SCI, osmotic pumps were implanted for seven-day continuous intrathecal administration of Shh. Basso, Beattie and Bresnahan (BBB) score, Gridwalk test and bodyweight were weekly assessed. Animals were sacrificed six weeks after SCI and immunohistological analyses were conducted. The results were compared between groups and statistical analysis was performed (p < 0.05 was considered significant). Results The intrathecal administration of Shh led to significantly increased polarization of macrophages toward the anti-inflammatory M2-phenotype, significantly decreased T-lymphocytic invasion and significantly reduced resident microglia six weeks after the injury. Reactive astrogliosis was also significantly reduced while changes in size of the posttraumatic cyst as well as the overall macrophagic infiltration, although reduced, remained insignificant. Finally, with the administration of Shh, gain of bodyweight (216.6 ± 3.65 g vs. 230.4 ± 5.477 g; p = 0.0111) and BBB score (8.2 ± 0.2 vs. 5.9 ± 0.7 points; p = 0.0365) were significantly improved compared to untreated animals six weeks after SCI as well. Conclusion Intrathecal Shh-administration showed neuroprotective effects with attenuated neuroinflammation, reduced astrogliosis and improved functional recovery six weeks after severe contusion/compression SCI.


1994 ◽  
Vol 80 (1) ◽  
pp. 97-111 ◽  
Author(s):  
Shlomo Constantini ◽  
Wise Young

✓ Recent clinical trials have reported that methylprednisolone sodium succinate (MP) or the monosialic ganglioside GM1 improves neurological recovery in human spinal cord injury. Because GM1 may have additive or synergistic effects when used with MP, the authors compared MP, GM1, and MP+GM1 treatments in a graded rat spinal cord contusion model. Spinal cord injury was caused by dropping a rod weighing 10 gm from a height of 1.25, 2.5, or 5.0 cm onto the rat spinal cord at T-10, which had been exposed via laminectomy. The lesion volumes were quantified from spinal cord Na and K shifts at 24 hours after injury and the results were verified histologically in separate experiments. A single dose of MP (30 mg/kg), given 5 minutes after injury, reduced 24-hour spinal cord lesion volumes by 56% (p = 0.0052), 28% (p = 0.0065), and 13% (p > 0.05) in the three injury-severity groups, respectively, compared to similarly injured control groups treated with vehicle only. Methylprednisolone also prevented injury-induced hyponatremia and increased body weight loss in the spine-injured rats. When used alone, GM1 (10 to 30 mg/kg) had little or no effect on any measured variable compared to vehicle controls; when given concomitantly with MP, GM1 blocked the neuroprotective effects of MP. At a dose of 3 mg/kg, GM1 partially prevented MP-induced reductions in lesion volumes, while 10 to 30 mg/kg of GM1 completely blocked these effects of MP. The effects of MP on injury-induced hyponatremia and body weight loss were also blocked by GM1. Thus, GM1 antagonized both central and peripheral effects of MP in spine-injured rats. Until this interaction is clarified, the authors recommend that MP and GM1 not be used concomitantly to treat acute human spinal cord injury. Because GM1 modulates protein kinase activity, protein kinases inhibit lipocortins, and lipocortins mediate anti-inflammatory effects of glucocorticoids, it is proposed that the neuroprotective effects of MP are partially due to anti-inflammatory effects and that GM1 antagonizes the effects of MP by inhibiting lipocortin. Possible beneficial effects of GM1 reported in central nervous system injury may be related to the effects on neural recovery rather than acute injury processes.


1999 ◽  
Vol 6 (1) ◽  
pp. E10 ◽  
Author(s):  
Charles H. Tator ◽  
Michael G. Fehlings

In this paper the authors review the clinical trials of neuroprotection that have been performed for the treatment of acute spinal cord injury (SCI). The biological rationale for the selection of each treatment modality is discussed with reference to current knowledge of the principles in the management of acute SCI as well as the primary and secondary injury mechanisms identified by experimental and clinical studies of the pathophysiology of acute SCI. The trials are evaluated with regard to the availability and use of accurate clinical outcome measures, and the methodologies of the trials are critically evaluated with an emphasis on prospective randomized controlled studies. A detailed description and critical analysis are provided of the results of the 10 clinical trials conducted to date in which a randomized prospective controlled design has been used. The issue of the therapeutic time window in acute SCI is discussed. To date, methylprednisolone is the only effective neuroprotective agent that has been established for use in human SCI, and the only therapeutic time window established in human SCI is a maximum trauma-to-treatment time of 8 hours.


2020 ◽  
Vol 37 (8-9) ◽  
pp. 2551-2577
Author(s):  
Andrew M. Ledbetter ◽  
Kristen Carr ◽  
Gentry Lynn

Using a sample of 312 people in a romantic relationship with a partner who has a spinal cord injury (SCI), this study examined the separate and combined effects of caregiving tasks, resilience, and received support on the participant’s level of psychosocial distress. We also tested whether such distress might mediate the effect of the predictors on romantic relationship closeness. Results supported the beneficial effects of both resilience and receiving high-quality support, although the timing of the injury moderated these effects. Injuries sustained after relationship initiation particularly threaten well-being and closeness and, along with the burden of caregiving tasks, alter the extent to which received support and resilience are associated with health and relationship benefits. These results suggest that support providers should be sensitive to the context of the SCI and, for scholars, indicate the importance of further theorizing context in the theory of resilience and relational load.


2007 ◽  
Vol 25 (9) ◽  
pp. 2927-2934 ◽  
Author(s):  
Antonio Castro ◽  
Fernando Díaz ◽  
Geert J. M. Van Boxtel

2020 ◽  
Vol 15 (10) ◽  
pp. 1912 ◽  
Author(s):  
Bo-Tao Tan ◽  
Hui Jiang ◽  
AaronJ Moulson ◽  
Xiao-Liang Wu ◽  
Wen-Chun Wang ◽  
...  

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