Department of Anesthesia, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, New Brunswick, NJ 08901-1977, USA.
J Neurol Sci. 2011 Feb 15;301(1-2):66-70. doi: 10.1016/j.jns.2010.10.024. Epub 2010 Nov 20.
In cerebral ischemia, transmission by the inhibitory neurotransmitter, γ-aminobutyric acid (GABA) is altered. This study was performed to determine whether blockade of GABA(A) receptor would affect regional cerebral blood flow (rCBF) and blood-brain barrier (BBB) permeability in a focal ischemic area of the brain. Rats were anesthetized with isoflurane and mechanically ventilated. Fifteen minutes after a permanent middle cerebral artery (MCA) occlusion, one half of the rats were infused with bicuculline 1mg/kg/min iv for 2 min followed by 0.1mg/kg/min iv to the end of the experiment. The other half were infused with normal saline. At one hour after MCA occlusion, rCBF was determined using ¹⁴C-iodoantipyrine and BBB permeability was determined by measuring the transfer coefficient (Ki) of ¹⁴C-α-aminoisobutyric acid. With MCA occlusion, rCBF was decreased in the ischemic cortex (IC) (-70%) in the control rats. In the bicuculline treated rats, the rCBF of the IC was lower (-48%) than the contralateral cortex but higher than the rCBF of the IC of the control rats (+55%). MCA occlusion increased Ki in the IC of the control rats (+72%) and bicuculline administration increased Ki further (+53%) in the IC. Blockade of GABA(A) receptors did not significantly affect rCBF or BBB permeability in the non-ischemic brain regions under isoflurane anesthesia. Our data demonstrated that blockade of GABA(A) receptors increased rCBF and enhanced the BBB disruption in focal cerebral ischemia. Our data suggest that GABA(A) receptors are involved, at least in part, in modulating rCBF and BBB disruption in focal cerebral ischemia.
在脑缺血中，抑制性神经递质γ-氨基丁酸（GABA）的传递发生改变。本研究旨在确定 GABA(A)受体阻断是否会影响大脑局灶性缺血区的局部脑血流(rCBF)和血脑屏障(BBB)通透性。大鼠用异氟烷麻醉并机械通气。大脑中动脉（MCA）永久性闭塞 15 分钟后，一半大鼠静脉输注双氢克尿噻 1mg/kg/min 2 分钟，然后以 0.1mg/kg/min 持续至实验结束。另一半大鼠输注生理盐水。MCA 闭塞 1 小时后，用¹⁴C-碘安替比林测定 rCBF，用¹⁴C-α-氨基异丁酸测定转移系数（Ki）来测定 BBB 通透性。在对照大鼠中，MCA 闭塞导致缺血皮质（IC）的 rCBF 降低（-70%）。在双氢克尿噻处理的大鼠中，IC 的 rCBF 低于对侧皮质（-48%），但高于对照大鼠 IC 的 rCBF（+55%）。MCA 闭塞增加了对照大鼠 IC 中的 Ki（+72%），而双氢克尿噻给药进一步增加了 IC 中的 Ki（+53%）。GABA(A)受体阻断在异氟烷麻醉下对非缺血脑区的 rCBF 或 BBB 通透性没有显著影响。我们的数据表明，GABA(A)受体阻断增加了局灶性脑缺血中的 rCBF，并增强了 BBB 破坏。我们的数据表明，GABA(A)受体至少部分参与了调节局灶性脑缺血中的 rCBF 和 BBB 破坏。
