Effect of hypothermia on apoptosis in traumatic brain injury and hemorrhagic shock model.

Introduction: The neuroprotective mechanisms of therapeutic hypothermia against trauma-related injury have not been fully understood yet. In this study, we aimed to investigate the effects of therapeutic hypothermia on biochemical and histopathological markers of apoptosis using Traumatic brain injury (TBI) and hemorrhagic shock (HS) model.

Methods: A total of 50 male albino-wistar rats were divided into five groups: Group isolated TBI, Group NT (HT+HS+normothermia), Group MH (HT+HS+mild hypothermia), Group MoH (HT+HS+moderate hypothermia) and Group C (control). Neurological deficit scores were assessed at baseline and at 24h. The rats were, then, sacrificed to collect serum and brain tissue samples. Levels of Caspase-3,6,8, proteoglycan-4 (PG-4), malondialdehyde (MDA), and nitric oxide (NO) were measured in serum and brain tissue samples. Histopathological examination was performed in brain tissue.

Results: There were significant differences in the serum levels of Caspase-3 between Group NT and Group C (p=0.018). The serum levels of Caspase-6 in Group NT (0.70±0.58) were lower than Group MH (1.39±0.28), although the difference was not statistically significant (p=0.068). There were significant differences in the brain tissue samples for Caspase-3 levels between Group NT and Group C (p=0.049). A significant difference in the Caspase-8 brain tissue levels was also observed between Group NT and Group C (p=0.022). Group NT had significantly higher scores of all the pathological variables (for edema p<0.017; for gliosis p<0.001; for congestion p<0.003, for hemorrhage p<0.011) than Group C.

Conclusion: Our study results suggest that hypothermia may exert its neuroprotective effects by reducing markers of apoptotic pathway, particularly Caspase-3 on TBI and HS.