A mouse model of embolic focal ischemic stroke for investigation of anti-thrombotic therapies

Abstract

[ACCESS RESTRICTED TO THE UNIVERSITY OF MISSOURI AT REQUEST OF AUTHOR.] Stroke is the third leading cause of death in the United States and the major cause of adult disability. Ischemic stroke accounts for about 87 percent of all cases, and is a condition in which there is insufficient blood flow and poor oxygen supply to the brain to meet metabolic demand, thus causing complex pathophysiology and damage to neurons and glial cells. Release of excitatory neurotransmitters such as glutamate and activation of ionotropic glutamate receptors such as that mediated by N-methyl-D-aspartic acid (NMDA) contribute to influx of calcium and stimulation of a train of events leading to mitochondrial dysfunction and neuronal apoptosis. Ischemia also triggers activation of matrix metalloproteinases (MMPs), known to play a role in degradation of extracellular matrix and disruption of blood brain barrier (BBB) and induction of neuronal cell death. Even though there are several models to mimic the effects of ischemic stroke, the embolic focal cerebral ischemic model is unique and one representing the most relevant physiological changes of ischemic stroke in human. Therefore, this embolic ischemic model may be used to identify the ischemia/stroke-induced brain damage due to lack of oxygen supply and other physiological stress, and studies to investigate potential drugs or agents for therapeutic purposes.