Genetic Deficiency Of Î²2-Containing Nicotinic Receptors Attenuates Brain Injury In Ischemic Stroke
One of the major consequences of stroke is brain injury caused by glutamate-mediated excitotoxicity. Glutamate-mediated excitatory activities are partially driven by Î²2-containing nicotinic acetylcholine receptors (Î²2-nAChRs). In examining the role of Î²2-nAChRs in cerebral ischemic injury, excitotoxicity and stroke outcome, we found that deficiency of Î²2-nAChRs attenuated brain infarction and neurological deficit at 24 and 72h after transient middle cerebral artery occlusion (MCAO). Genetic deletion of Î²2-nAChRs associated with reduced terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick-end labeling (TUNEL+) and cleaved caspase-3+ cells after MCAO, together with a reduction of extracellular glutamate and oxygen-glucose deprivation-induced increase of excitatory inputs in cortical neurons. Pharmacologic pretreatment with a selective Î²2-nAChRs antagonist reduced brain infarction, neurological deficit, and MCAO-induced glutamate release. These findings suggest that deficiency of Î²2-nAChRs, also achievable by pharmacological blockade, can decrease brain infarction and improve the neurological status in ischemic stroke. The improved outcome is associated with reduced extracellular glutamate level and lower excitatory inputs into ischemic neurons, suggesting a reduction of glutamate-mediated excitotoxicity in the mechanisms of neuroprotection. Â© 2013 IBRO.
Digital Object Identifier (DOI)
Liu, Q.; Tang, Z.; Gan, Y.; Wu, W.; Kousari, A.; Cava, A. La; and Shi, F. D., "Genetic Deficiency Of Î²2-Containing Nicotinic Receptors Attenuates Brain Injury In Ischemic Stroke" (2014). Translational Neuroscience. 144.