The Exploration Of Regional Profound Hypothermia’s Effects On Axon Regeneration And The Possible Molecular Mechanisms

Background context and purpose:Spinal cord injury (SCI) is a catastrophic neurological event mainly caused by motor vehicle accidents, tumble injuries, sports accidents and violence. SCI often causes lifelong dysfunction to the patients and seriously affecting the quality of life,not to mention the giant burden on the national health care system.At present, the treatment of spinal cord injury is still a difficult problem to the clinicians, conventional treatment methods such as decompression and internal fixation, glucocorticoid and ganglioside have failed to get an encouraging curative effect. In addition, some auxiliary treatment measures such as hyperbaric oxygen, stem cell transplantation have been used in the treatment of SCI, of which hypothermia have been proven to have a certain therapy effect and widely used in cardiac arrest hypoxic ischemic encephalopathy, aortic aneurysm surgery, spinal cord injury and traumatic brain injury. However, some controversial issues remain to be solved, such as the temperature range, the detrimental consequences, the introducing methods and the duration of hypothermia.according to the existing small clinical trials, systematic hypothermia could not only increase the incidence of cardiac arrhythmias and pneumonia, but also cause serious consequences such as chills, immunosuppression, electrolyte disorder and mild coagulopathy. Regional hypothermia can largely avoid the complications mentioned above and achieve a lower temperature range compared with systematic hypothermia.After spinal cord injury, chondroitin sulfate proteoglycans(CSPGs), Nogo-A can suppress the nerve regeneration through activating the RhoA-ROCK pathway. Although the effects of hypothermia on the inflammatory response and apoptosis have been intensively studied, the effects of hypothermia on nerve regeneration after spinal injury remains rarely investigated.The primary focus of this study was to determine the therapeutic efficacy of local Profound hypothermia on axon regeneration and explore the possible mechanism in adult rats with spinal cord injury.Study design and methods:Animals with TH10 compression injury were used in this study and an epidural perfusion device was applied to maintain a steady temperature (18℃) for 120min with gradual re-warming to 37 ℃. The expressions of axon regeneration inhibitors were tested by westernblot and real-time PCR. The Luxol Fast Blue (LFB) stain and Bielschowsky silver stain were used to observe the morphology features of spinal cord, in addition, the motor function of hind limbs (BBB score) was monitored for 21 days.Results:The expressions of RhoA, ROCK-II, NG2, Neurocan, Brevican and Nogo-A were downregulated by hypothermia after spinal cord injury, an alleviated demyelinating condition and more nerve fibers were observed in rats received regional hypothermia, in addition, the RH group got a higher BBB score compared with the SCI group.Conclusions:Local profound hypothermia can promotes axon regeneration and protect motor function, and this effect may caused by the suppression of axon regeneration inhibitors.