Importance of calcitonin gene-related peptide, adenosine and reactive oxygen species in cerebral autoregulation under normal and diseased conditions.
1. Mechanisms regulating cerebral circulation, including autoregulation of cerebral blood flow (CBF), have been widely investigated. Vasodilators such as nitric oxide, prostacyclin, calcitonin gene-related peptide (CGRP) and K+ channel openers are well known to have important roles in the physiological and pathophysiological control of CBF autoregulation. In the present review, the focus is on the mechanism(s) of altered CBF autoregulation after traumatic brain injury and subarachnoid haemorrhage (SAH) and on the effect of adenovirus-mediated transfer of Cu/Zn superoxide dismutase (SOD)-1 in amelioration of impaired CBF autoregulation. 2. The roles of CGRP and adenosine are particularly emphasized, both being implicated in the autoregulatory vasodilation of the pial artery in response to hypotension. 3. After fluid percussion injury, production of NADPH oxidase-derived superoxide anion and activation of tyrosine kinase links the inhibition of K+ channels to impaired autoregulatory vasodilation in response to acute hypotension and alterations in CBF autoregulation in rat pial artery. 4. Subarachnoid haemorrhage during the acute stage causes an increase in NADPH oxidase-dependent superoxide formation in cerebral vessels in association with activated tyrosine phosphorylation-coupled increased expression of gp91phox mRNA and membrane translocation of Rac protein, thereby resulting in a significant reduction of autoregulatory vasodilation. 5. Fluid percussion injury and SAH-induced overproduction of superoxide anion in cerebral vessels contributes to the impairment of CBF autoregulation and administration of recombinant adenovirus-mediated transfer of the Cu/Zn SOD-1 gene effectively ameliorates the impairment of CBF autoregulation of the pial artery.
Shin
Hwa Kyoung
HK
Department of Pharmacology, College of Medicine, Research Institute of Genetic Engineering, Pusan National University, Ami-Dong 1-Ga, Seo-Gu, Pusan 602-739, Korea.
Hong
Ki Whan
KW
D000241:Adenosine / Q000502:physiology*; D001921:Brain / Q000502:physiology*; D015740:Calcitonin Gene-Related Peptide / Q000502:physiology*; D002560:Cerebrovascular Circulation; D004194:Disease; D015316:Genetic Therapy; D006706:Homeostasis; D006801:Humans; D017382:Reactive Oxygen Species; D013482:Superoxide Dismutase / Q000235:genetics
D017382:Reactive Oxygen Species; D013482:Superoxide Dismutase; D015740:Calcitonin Gene-Related Peptide; D000241:Adenosine