Effects of GABA A receptor blockade on regional cerebral blood flow and blood–brain barrier disruption in focal cerebral ischemia

Abstract

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 1 mg/kg/min iv for 2 min followed by 0.1 mg/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.