Nitric oxide production during focal cerebral ischemia in rats.

Abstract

Background and Purpose: Nitric oxide has been implicated as a mediator of glutamate excitotoxicity in primary neuronal cultures.Methods: A number of indicators of brain nitric oxide production (nitrite and cyclic guanosine monophosphate [cGMP] concentrations and nitric oxide synthase activity) were examined after bilateral carotid ligation and right middle cerebral artery occlusion in adult rats.Results: Brain nitrite was significantly increased in the right versus left cortex 5, 10, and 20 minutes after middle cerebral artery occlusion (P<.05), with a return to baseline at 60 minutes. There were no significant changes in cerebellar concentrations. Cortical levels of cGMP were increased at 10, 20, and 60 minutes after occlusion, with significant right-to-left differences (P<.05). Cerebellar concentrations of cGMP were also increased but without significant side-to-side differences. Nitric oxide synthase activity increased approximately 10-fold from baseline 10 minutes after occlusion in the right cortex but decreased markedly by 60 minutes from its peak at 10 minutes. The right-to-left difference in nitric oxide synthase activity was significant at 20 minutes (P<.05). Pretreatment of rats with NG-nitro-L-arginine, a nitric oxide synthase inhibitor, abolished the rise in nitrite and cGMP.Conclusions: These results suggest that a sharp transient increase in the activity of nitric oxide synthase occurs during the first hour of cerebral ischemia, which leads to a burst in nitric oxide production and activation of guanylate cyclase. (Stroke. 1993;24:1709-1716 KEY WORDs * cerebral arteries * cerebral ischemia * nitric oxide

Nitric Oxide: Considerations for the Treatment of Ischemic Stroke

“…Occlusion of the middle cerebral artery (MCAo) results in an increased production of NO by 20-fold for up to 30 minutes (Malinski et al, 1993;Kader et al, 1993) most likely through increased calcium availability and activation of nNOS (Huang et al, 1994). Thereafter, the brain tissue NO is reduced below detectable levels for up to 7 days (Malinski et al, 1993;Sugimura et al, 1998), indicating a long-lasting NO deficiency in the ischemic brain.…”

“…If reperfusion occurs, NO concentration may transiently increase by 50% for about 30 minutes (Fassbender et al, 2000;Uetsuka et al, 2002). Concomitant with changes in NO levels, the activities of eNOS and nNOS increases within the first few minutes after MCAo, but decrease significantly thereafter (Kader et al, 1993). In contrast to the constitutive NOS isoforms, iNO becomes upregulated from 12 hours after MCAo for up to 7 days (Niwa et al, 2001).…”

Improved functional outcome after spinal cord injury in iNOS-deficient mice

“…After experimental ischaemic and traumatic brain damage, there is a rapid and transient increase in the catalytic activity of constitutive NOS, 2,3 followed by induction of iNOS with some delay. 4,5 Based on the findings obtained with pharmacological inhibition of NOS or comparisons between NOS-deficient and wildtype mice, both protective 3,6 and harmful [3][4][5] effects of NO in experimental CNS injury have been demonstrated.…”

Cerebral protection in experimental cardiopulmonary resuscitation (with special reference to the effects of methylene blue)

“…Reperfusion is often hyperemic in the first few minutes after CA because of elevated CPP and impaired cerebrovascular autoregulation [6], which is either absent or right-shifted [71]. The high levels of NO produced during ischemia and early reperfusion may caused cerebral hyperemia [72,74]. Hyperemia may be detrimental to cells, especially in the brain parenchyma, by causing disruption of the BBB, which may ultimately worsen neurological injury [74].…”