ABSTRACT
Aims: Neurotransmitter overflow into the extracellular space and activation of nitric oxide synthase were implicated in neuronal death after cerebral ischemia. A small temperature reduction induced after the insult crucially mitigated the neuronal death. To elucidate the mechanisms, dopamine and glutamate as marker of excitatory amino acid (EAA) overflow and the citrulline/arginine ratio (CAR) as marker of nitric oxide synthase were analysed. Study Design: Animal experiments in rats. Place and Duration of the Study: Laboratory of the Department of Pharmaceutical Chemistry and Drug Analysis, Vrije Universiteit Brussel, Brussels between 2001 and 2003. Methodology: Striatal Glutamate and dopamine and CAR were measured by using microdialysis under normothermic and hypothermic conditions before asphyxial cardiac arrest, during the insult and resuscitation as well as during the weaning process from mechanical ventilation. Results: After the insult, the EAA overflow increased significantly in the normothermic group. In the hypothermic group, however this overflow was not significantly different from the sham group. The CAR increased up to 5-fold compared to the basal value in the normothermic group and only 2.5-fold in the hypothermic group. The brain damage was mitigated in the hypothermic group, while this increased further up 7 days after the insult in the normothermic group. Conclusion: These results suggest that the neuroprotective effect of mild hypothermia resides in attenuation of the striatal EAA overflow and diminution of the CAR and were associated with a reduction of brain damage at 24 hours and 7 days post insult.