Abstract
Nitric oxide (NO) is a gaseous chemical messenger which has functions in the brain in a variety of broad physiological processes, including control of cerebral blood flow, interneuronal communications, synaptic plasticity, memory formation, receptor functions, intracellular signal transmission, and release of neurotransmitters. As might be expected from the numerous and complex roles that NO normally has, it can have both beneficial and detrimental effects in disease states, including traumatic brain injury. There are two periods of time after injury when NO accumulates in the brain, immediately after injury and then again several hours-days later. The initial immediate peak in NO after injury is probably due to the activity of endothelial NOS and neuronal NOS. Pre-injury treatment with 7-nitroindazole, which probably inhibits this immediate increase in NO by neuronal NOS, is effective in improving neurological outcome in some models of traumatic brain injury (TBI). After the initial peak in NO, there can be a period of relative deficiency in NO. This period of low NO levels is associated with a low cerebral blood flow (CBF). Administration of L-arginine at this early time improves CBF, and outcome in many models. The late peak in NO after traumatic injury is probably due primarily to the activity of inducible NOS. Inhibition of inducible NOS has neuroprotective effects in most models.