Effects of Exogenous Excitatory Amino Acid Neurotransmitters on Blood–Brain Barrier Disruption in Focal Cerebral Ischemia

Abstract

This study was performed to determine whether exogenous N-methyl-D: -aspartate (NMDA) or alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) would aggravate blood-brain barrier (BBB) disruption in focal cerebral ischemia in rats. Forty-five minutes after middle cerebral artery (MCA) occlusion, one of the following patches was applied to the exposed ischemic cerebral cortex of each rat: normal saline (control), 10(-5) M AMPA, 10(-4) M AMPA, 10(-5) M NMDA, or 10(-4) M NMDA. At 1 h after MCA occlusion, BBB permeability was determined by measuring the transfer coefficient (Ki) of (14)C-alpha-aminoisobutyric acid ((14)C-AIB). In all experimental groups, the Ki of the ischemic cortex (IC) was higher than that of the corresponding contralateral cortex (CC). The Ki of the IC of the animals treated with 10(-4) M AMPA or 10(-4) M NMDA was higher (+41%: P < 0.05 and +33%: P < 0.05, respectively) than that of the control animals. Our data demonstrated that exogenous NMDA or AMPA could further aggravate the BBB disruption in focal cerebral ischemia. Any insult increasing the release of excitatory neurotransmitters could further aggravate BBB disruption and brain edema during the ischemic period.

Astragaloside IV reduces cerebral edema post-ischemia/reperfusion correlating the suppression of MMP-9 and AQP4

“…Abundant evidence demonstrated that BBB disruption induced by I/R injury contributes to vasogenic brain edema, aggravating the ischemic brain damage eventually (Chi et al, 2009;Gidday et al, 2005). Matrix metalloproteinases (MMPs), a family of proteolytic enzymes, were reported to degrade several important structural proteins in the microvascular wall, resulting in an increase of the microvascular permeability and BBB disruption (Gidday et al, 2005;Piao et al, 2009).…”

Effect of Baicalin on Matrix Metalloproteinase-9 Expression and Blood–Brain Barrier Permeability Following Focal Cerebral Ischemia in Rats

“…Abundant evidence demonstrates that cerebral ischemiainduced BBB disruption contributes to vasogenic brain edema and neutrophil infiltration, eventually aggravating the ischemic brain damage [5,6]. Matrix metalloproteinases (MMPs), a family of proteolytic enzymes, are reported to degrade important structures in the microvascular wall, resulting in an increase of the microvascular permeability and BBB disruption [7,8].…”

Loss of Integrity: Impairment of the Blood-brain Barrier in Heavy Metal-associated Ischemic Stroke

“…Since BBB permeability plays a crucial role in determination of the extent of ischemic brain damage, factors that modify the susceptibility of BBB integrity can alter the overall outcome of ischemic stroke. Hyperglycemia significantly worsened BBB breakdown during ischemic condition, contributing to the aggravation of the consequences of stroke (57), and exogenous excitatory amino acid neurotransmitters disrupted BBB integrity during focal cerebral ischemia (58). Although the studies investigating the effect of heavy metals on BBB integrity are limited, several reports have given insights for heavy metalinduced BBB disruption (59).…”