The Role of Nitric Oxide in Cerebral Ischemia

Abstract

This chapter explores the role of nitric oxide (NO) in cerebral ischemia. The free radical gas of nitric oxide is synthesized in neurons, glia, perivascular nerves, cerebrovascular endothelium, macrophages, and white blood cells from the amino acid L-arginine and molecular oxygen by the enzyme, nitric oxide synthase (NOS). At least three isoforms of NOS have been identified: neuronal and endothelial isoforms that are constitutively expressed and encoded on chromosomes 12 and 7, respectively, and an inducible isoform encoded on chromosome 17. Experimental results show that within 3–24 min after middle cerebral artery (MCA) occlusion, NO increases dramatically within cortex as detected by a porphyrinic microsensor. It is believed that constitutive NOS activity increases during ischemia due to a rise in intracellular Ca 2+ . Constitutive NOS (endothelial and neuronal isoforms) is activated by intracellular calcium concentrations slightly above the resting level and is maximally stimulated at levels well below those reached in neurons during focal ischemia. A late but sustained increase in NO levels may also occur due to expression of inducible NOS (Ca 2+ -independent isoform) within microglia and invading inflammatory cells 24 h after the induction of ischemia.