Cerebral blood flow regulation by nitric oxide in neurological disorders

Abstract

There has been a rapid increase in the amount of information on the physiological and pathophysiological roles of nitric oxide (NO) in the brain. This molecule, which is formed by the constitutive isoforms of NO synthase, endothelial (eNOS) and neuronal (nNOS), plays an obligatory role in the regulation of cerebral blood flow and cell viability and in the protection of nerve cells or fibres against pathogenic factors associated with Alzheimer's disease, Huntington's disease, seizures, and migraine. Cerebral blood flow is impaired by decreased formation of NO from endothelial cells, autonomic nitrergic nerves, or brain neurons and also by increased production of reactive oxygen species (ROS). The NO-ROS interaction is an important topic in discussing blood flow and cell viability in the brain. Excessive production of NO by inducible NOS (iNOS) and nNOS in the brain participates in neurotoxicity. Recent studies on brain circulation have provided useful information about the involvement of impaired NO availability or uncontrolled NO production in cerebral pathogenesis, including Alzheimer's disease, seizures, vascular headaches, and inflammatory disorders. Insight into the role of NO in the brain will contribute to our better understanding of cerebral hemodynamic dysfunction and will aid in developing novel therapeutic measures in diseases of the central nervous system.

Effects of voluntary exercise on structure and function of cortical microvasculature

“…119 We speculate that NO signaling may be the mediator of the arteriolar desensitization given its involvement in hypercapnic vasodilation. 120,121 This hypothesis is motivated by prior demonstrations of exercise-induced increase in the availability of NO, which may induce short-term dilation, 38,122 followed by long-term desensitization of smooth muscle cells to NO elevations. 123 In addition to arteriolar desensitization to CO 2 , we speculate that the chronic elevation in cortical activity as a result of exercise may also have led to the adaptation of the cortical metabolism, possibly by utilization of greater relative amounts of lactate-toglucose 119 and hence allowing the brain to perform the same amount of ''input processing'' despite attenuated blood flow increase to the input stimulus and thus attenuated stimulation-induced increase in metabolite delivery.…”

Increased asymmetric dimethylarginine and nitric oxide levels in patients with migraine

“…In some studies, oxidative stress due to increased NO has been found especially during attacks in patients with migraine [4,5]. It is emphasized that neurogenic inflammation, endothelial dysfunction and oxidative stress have a role in migraine pathogenesis [1][2][3][4][5].…”

Serum L-arginine and dimethylarginine levels in migraine patients with brain white matter lesions

“…NO is produced by vascular endothelial cells, and plays a crucial role in the regulation of blood pressure, cerebral blood flow and neuroprotection (18,33). The amino acid L-arginine is the main precursor of NO (Figure 3) (20,34).…”

“…Endothelial NO-synthase (eNOS) utilizes L-arginine to generate the strong vasodilator, anti-atherogenic NO (18). Methylated analogs of L-arginine, symmetric and asymmetric dimethylarginine (SDMA and ADMA) are modulators of the L-arginine/NO pathway (19,20).…”