Molecular and Biochemical Events Within the Brain Subjected to Cerebral Ischemia (targets for Therapeutical Intervention)

We review the molecular and biochemical events that occur within the brain during cerebral ischemia, based on recent investigations of focal cerebral ischemia models. Occlusion of the middle cerebral artery in rats produces focal ischemia. In contrast to the core where ischemia is severe and infarction develops rapidly, areas surrounding the core (called the penumbra) show a more moderate decrease of blood flow and can tolerate longer durations of ischemic stress. Reperfusion and pharmacological interventions can help to salvage the penumbra. Ischemic insult alters the genomic properties of the brain cells and selective production of heat shock proteins can be seen. Heat shock proteins are necessary in the repair of cell integrity, and is thought to be induced as a rescue program. Pre-ischemic induction of these proteins is known to cause ischemic tolerance, and methods to manipulate genes into inducing HSPs may be effective in protecting neurons from ischemia. Genes that promote apoptosis are also expressed after ischemia, and may cause secondary expansion of the infarction. Strategies to denote expression of these genes may be effective in reducing ischemic neuronal death. Activation of the inflammatory cells such as neutrophils and macrophages, in the ischemic region, may cause further post-ischemic damage. Investigations on the role and mechanics of inflammatory systems in ischemic neuronal injury may present a new target for therapeutic intervention against stroke.