0303

EFFECTS OF NIMODIPINE AND KETAMINE ON [Ca2+]I AND DELAYED NEURONAL DEMAGE FOLLOWING GLOBAL CEREBRAL ISCHEMIA IN RABBITS

He Y-X2, Fan X-M1, Qian S-Y1, Shen H-Q1

1 Beijing Children��s Hospital, Beijing, China

2 Hebei Children��s Hospital, Shijiazhuang, China

 

Objective: To investigate effects of nimodipine and ketamine on intracellular free calcium [Ca2+]I and delayed neuronal damage following global cerebral ischemia in rabbits .

Methods: 30 minutes global cerebral ischemia was induced by 4-vessel occlusion. 60 rabbits were randomly divided into sham-operated, ischemia, nimodipine, ketamine and both agents in combination groups (n=12 for each). Treatments were started at 30 minutes after reperfusion and continued till 6 hours after reperfusion by iv. 6 rabbits of each group were killed at 6 hrs after reperfusion to test [Ca2+]I in hippocampus. Remaining 6 rabbits of each group were killed at 7 days after ischemia for TUNEL and light and electrical microscope observation.

Results: Ischemia induced significant increase of [Ca2+]I in hippocampus (P=0.000). Nimodipine and ketamine singly or in combination significantly decreased the increase (P=0.000). 7 days after ischemia there were lots of TUNEL positive neurons, neuronal loss in CA1 of hippocampus (P=0.000) and obvious histologic damage. Ketamine signifincantly reduced TUNEL reaction, neuronal loss (P=0.000) and histologic damage. Nimodipine had less effect on neuronal loss (P=0.044), weak effect on ultrastructure and no effects on TUNEL. Combined therapy reduced TUNEL reaction and neuronal loss but had limited effects on histology.

Conclusions: Increasing of [Ca2+]I plays a key role in delayed ischemic neuronal damage. Ketamine is a potent neuroprotectant. Despite decresing [Ca2+]I nimodipine has little neuroprotection. No synergetic effect was observed in combination therapy.