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Keywords:

  • brain damage;
  • hypothermia;
  • neonate;
  • nitric oxide;
  • seizure

Abstract Background: The aim of the present study was to investigate whether rapid rewarming after hypothermia therapy during seizures alters the endogenous nitric oxide (NO) production in and around hippocampus, cortical cerebral blood flow (cCBF), and mean arterial blood pressure (MABP) in immature rabbits.

Methods: The hypothermic rabbits (rectal temperatures, 33°C) were given kainic acid (KA; 12 mg/kg, i.v; at 0 min), followed by cooling (33°C) for 60 min (at 60 min), then either rewarming (RW; 33–37°C) was started (KA[+]RW[+] group, n = 7) or cooling was continued (KA[+]RW[–] group, n = 7) for another 60 min (at the end 120 min). In the KA(–)RW(+) group (n = 5), 0.5 mL normal saline was given (at time 0 min), followed by cooling (33°C) for 60 min (at 60 min), then rewarming to 37°C was started with observation for another 60 min (at the end 120 min). NO production in and around hippocampus was continuously measured by an NO-selective electrode, cCBF by laser Doppler flowmetry, cortical electroencephalogram (EEG), rectal and cerebral temperatures, and MABP during the experiment. Comparisons were made of these parameters between the values at 60 min and 120 min after the KA administrations.

Results: KA administration induced abnormal discharges in both KA(+)RW(+) and KA(+)RW(–) groups at the same degree. The KA(+)RW(+) group had a significant increase in %NO, and significant decreases in %cCBF and MABP after rapid rewarming, compared with before rewarming. In the KA(+)RW(–) group, there were no significant changes in %NO, %cCBF, and MABP between values at 60 and 120 min. These changes after rapid rewarming in the KA(+)RW(+) group were different from those with only elevation in brain temperature from 33 to 37°C without seizures (KA[–]RW[+] group).

Conclusions: These results suggest that rapid rewarming after hypothermia therapy induces an increase in the NO production in and around hippocampus and the decreases in cCBF and MABP during seizures in immature rabbits.