Introduction/Rational: Traumatic injuries to the central nervous system (CNS) occurring at cold or hot environments may affect the pathological outcome. In addition, this is not known whether injuries at these ambient temperatures may also affect the therapeutic potential of the drug treatments. Military personnel engaged in combat operations are often exposed to high environmental heat and thus under such situations if they are inflicted with trauma to the CNS their pathological outcome and drug therapy requires further investigation. In this investigation pathology and pharmacology of a focal spinal cord injury (SCI) at high environment was examined in a model experiment.

Method/Approach: SCI was produced in Equithesin anesthetized rats either at room temperature (21 ± 1°C) or animals exposed to 38°C 1 h daily for 1 week by making a longitudinal incision (4 mm long and 2 mm deep) of the right dorsal horn of the T10-11 segments. In separate groups, Cerebrolsyin (2.5 ml or 5 ml/kg; Ever NeuroPharma, Austria) either as such or with TiO2 nanowired formulations was delivered intravenously 4 and 8 after SCI. After 48 h SCI blood-spinal cord barrier (BSCB), edema and neuronal injuries were examined. Uninjured animals at room or hot temperatures served as controls.

Results/Effects: A focal SCI inflicted at hot environment resulted in marked exacerbation of BSCB breakdown to Evans blue albumin, edema formation and neuronal injuries as compared to identical SCI at room temperature. Treatment with 2.5 ml/kg cerebrolysin resulted in good neuroprotection in SCI at room temperature. However, either TiO2 nanowired cerebrolysin (2.5 ml) or higher dose of the drug (5 ml/kg) is needed to induce significant neuroprotection in SCI at inflicted at hot environment. TiO2 nanowires alone or TiO2 nanowired cerebrolysin did not influence cord pathology in normal animals at room temperature or at hot environment.

Conclusions/Limitations: These observations are the first to demonstrate that SCI occurring at hot environments exacerbate pathological outcome. Furthermore injuries inflicted at hot temperatures require either higher doses of the therapeutic agents or their delivery through nanotechnologies to induce good neuroprotection, not reported earlier. It would be interesting to find out whether TiO2 nanowired cerebrolysin if given 12 to 24 hours after SCI could also reduce the pathological outcome at 48 hours or longer durations.