Title: Effect of MK-801 on Caspase-3 Activation and Apoptosis after Cerebral Hypoxic-Ischemic Injury in Neonatal Rats
Abstract: Objective To study the effect of MK 801, the antagonist of NMDA receptor, on caspase 3 activation and apoptosis after cerebral hypoxic ischemic injury in neonatal rats. Methods Seven day old rat pups were injected with either 0.5 mg/kg MK 801 or normal saline immediately after cerebral hypoxic ischemic injury (HI). The pups were killed 24 h after the injection. Brain damage was evaluated using MAP 2 immunostaining. Caspase 3 activation was examined using anti p17 subunit antibody. Apoptosis was examined by in situ labeling of hairpin probe (HPP). The infarction area was calculated according to MAP 2 staining. Active caspase 3 cells and HPP positive cells were counted in the MAP 2 negative area of the cortex. Results The infarction area was reduced from (52±12)% to (23±5)% after the treatment with MK 801. A few caspase 3 and HPP positive cells were also found in the cortex of normal rat brains. The number of positive cells reached a peak at 24 h after HI. Both the number of caspase 3 (from 65±8 to 40± 6.7 per high power visual field) and HPP (from 61.6 ± 11.5 to 12.6 ± 5.2 per high power visual field) positive cells were decreased after the treatment with MK 801. Conclusions MK 801 inhibits caspase 3 activation and reduces the number of apoptotic cells. NMDA is involved in the activation of the apoptotic process in the immature brain after HI.
Publication Year: 2001
Publication Date: 2001-01-01
Language: en
Type: article
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