Babcock Alex M, Everingham Andi, Paden Charles M, Kimura Maki
Department of Psychology, Montana State University, Bozeman, Montana 59715, USA.
J Neurosci Res. 2002 Mar 15;67(6):804-11. doi: 10.1002/jnr.10169.
Excessive release of glutamate during transient cerebral ischemia initiates a cascade of events that leads to the delayed and selective death of neurons located in the hippocampus. Activity of calcium calmodulin kinase II (CaM kinase), a protein kinase critical to neuronal functioning, disappears following ischemia. The in vivo link between glutamate excitoxicity and alterations in CaM kinase activity has not been extensively studied. Baclofen, a selective gamma-aminobutyric acid (GABA)(B) receptor agonist, has been shown to inhibit glutamate release. The present study evaluated the neuroprotective efficacy of this compound and assessed early changes in hippocampal-dependent behaviors and CaM kinase immunoreactivity following transient cerebral ischemia. Baclofen (50 mg/kg) prevented both the loss of hippocampal CA1 pyramidal cells and the reduction in hippocampal CaM kinase immunoreactivity observed in control animals following ischemic insult. Cerebral ischemia produced a significant increase in working memory errors; however, baclofen failed to attenuate this memory deficit. Results confirm that baclofen is neuroprotective and support a link between glutamate excitotoxicity and reductions in CaM kinase immunoreactivity.
短暂性脑缺血期间谷氨酸的过度释放引发了一系列事件，导致海马区神经元的延迟性和选择性死亡。钙/钙调蛋白激酶II（CaM激酶）是一种对神经元功能至关重要的蛋白激酶，其活性在缺血后消失。谷氨酸兴奋性毒性与CaM激酶活性改变之间的体内联系尚未得到广泛研究。巴氯芬是一种选择性γ-氨基丁酸（GABA）（B）受体激动剂，已被证明可抑制谷氨酸释放。本研究评估了该化合物的神经保护作用，并评估了短暂性脑缺血后海马依赖性行为和CaM激酶免疫反应性的早期变化。巴氯芬（50毫克/千克）可防止缺血性损伤后对照动物海马CA1锥体细胞的丢失以及海马CaM激酶免疫反应性的降低。脑缺血导致工作记忆错误显著增加；然而，巴氯芬未能减轻这种记忆缺陷。结果证实巴氯芬具有神经保护作用，并支持谷氨酸兴奋性毒性与CaM激酶免疫反应性降低之间的联系。
