ABSTRACT
Ischemic stroke is commonly the outcome of obstruction of bloodflow in a major cerebral vessel (usually the middle cerebral artery), which, if not resolved within a short period of time, will lead to a core of severely ischemic brain tissue that may not be salvageable. The dynamic changes of brain tissue following ischemic stroke are illustrated in Fig. 23.1. Ischemic stroke leads to depletion of energy (ATP, phosphocreatine (PCr)) and hence to membrane voltage reduction, leading to ionic fluxes across the cell membrane. Extracellular potassium can reach levels sufficient to release neurotransmitters such as glutamate and aspartate and stimulate sodium/calcium channels coupled to glutamate
receptors, leading to cytotoxic edema. The calcium overload causes further mitochondrial damage and impairment in ATP production as well as extensive breakdown of cellular phospholipids, proteins and nucleic acids due to activation of phospholipases, proteases, and endonucleases. Free radicals are also produced during ischemia and contribute to membrane lipid peroxidation, protein and nuclear DNA toxic changes, and cellular injury (i.e. necrosis and apoptosis).
