CAJ | 학술논문

"氧糖剥夺"模型作为研究脑缺血的离体模型被广泛使用,该模型模拟了局灶性脑缺血的主要病理变化.然而在缺血病灶核心区与正常脑组织之间称为缺血半暗带的区域,脑血流也有程度不一的降低.为了模拟这种病理变化,发展了一种"不完全氧糖剥夺"的离体脑片模型,该模型满足两个条件,灌流液里氧气部分剥夺而葡萄糖含量降低;"氧糖剥夺"可以导致谷氨酸介导的兴奋性毒性,从而引起神经细胞的坏死.而A型γ-氨基丁酸受体(GABAAR)介导的神经元抑制性活动可以对抗谷氨酸引起的兴奋性毒性,因此近年来引起广泛的研究兴趣.而谷氨酸受体和γ-氨基丁酸受体功能在缺血半暗带是否有改变尚不得而知.因此本文采用海马脑片全细胞膜片钳的记录方法,研究"不完全氧糖剥夺"对海马CA1区神经元的A型γ-氨基丁酸受体介导的抑制性突触后膜电流(IPSCs)的影响.研究发现"不完全氧糖剥夺"使GABAAR介导的IPSCs的峰值增加而衰减时程延长.进一步研究发现该电流的峰值增加是由于GABAAR-氯离子通道的电导增加所致,而与氯离子的反转电位变化无关.这些发现提示在脑缺血的缺血半暗带区域GABAAR介导的神经元抑制性活动可能是增强的,这可能是神经元面对缺血状态产生自我保护的一种内稳态机制.
"양당박탈"모형작위연구뇌결혈적리체모형피엄범사용,해모형모의료국조성뇌결혈적주요병리변화.연이재결혈병조핵심구여정상뇌조직지간칭위결혈반암대적구역,뇌혈류야유정도불일적강저.위료모의저충병리변화,발전료일충"불완전양당박탈"적리체뇌편모형,해모형만족량개조건,관류액리양기부분박탈이포도당함량강저;"양당박탈"가이도치곡안산개도적흥강성독성,종이인기신경세포적배사.이A형γ-안기정산수체(GABAAR)개도적신경원억제성활동가이대항곡안산인기적흥강성독성,인차근년래인기엄범적연구흥취.이곡안산수체화γ-안기정산수체공능재결혈반암대시부유개변상불득이지.인차본문채용해마뇌편전세포막편겸적기록방법,연구"불완전양당박탈"대해마CA1구신경원적A형γ-안기정산수체개도적억제성돌촉후막전류(IPSCs)적영향.연구발현"불완전양당박탈"사GABAAR개도적IPSCs적봉치증가이쇠감시정연장.진일보연구발현해전류적봉치증가시유우GABAAR-록리자통도적전도증가소치,이여록리자적반전전위변화무관.저사발현제시재뇌결혈적결혈반암대구역GABAAR개도적신경원억제성활동가능시증강적,저가능시신경원면대결혈상태산생자아보호적일충내은태궤제.
Oxygen/glucose deprivation (OGD) has been widely used as an in vitro model of focal ischemia, where residual blood flow remains oxygen and glucose supplies are at low levels. To model this pathological genesis, we developed a partial OGD (pOGD) protocol in a rat brain slice. This model met two requirements: oxygen was partially deprived and glucose was reduced in the perfusion buffer. Therefore we investigated the effect of pOGD on gama-aminobutyric acid (GABAA) receptor-mediated inhibitory postsynaptic currents (IPSCs) in CA1 neurons of a hippocampal slice through whole-cell patch-clamp technique. We found that the amplitude and decay time of IPSCs were increased immediately during pOGD treatment. And the enhancement of IPSCs amplitude resulted from an increase of the synaptic conductance without a significant change in the reversal potential of chloride. These results suggested that the nervous system could increase inhibitory neurotransmission to offset excitation by homeostasis mechanisms during the partial oxygen and glucose attack.