ABSTRACT
Department of Cardiovascular Pharmacology, SmithKline Beecham Pharmaceuticals, King of Prussia, Pennsylvania
Ischemic injury to the central nervous system can lead to cell injury and death via a number of mechanisms, including excitotoxicity, intracellular calcium overload, inhibition of protein synthesis, cytokine-mediated inflammation, and loss of survival factors. These diverse injury mechanisms result in impaired cognitive abilities as well as compromised sensorimotor function. Traditionally, these deficits are attributed to a loss of neurons from passive necrotic death within the region of the ischemic insult. More recent work, however, has provided evidence that neurons are lost by active cell death, or apoptosis (Linnik et al., 1993; MacManus et al., 1994; Li et al., 1995; Namura et al., 1998; Chen et al., 1998).
