Multiparametric Responses to Cortical Spreading Depression Under Nitric Oxide Synthesis Inhibition

Abstract

Cortical spreading depression (SD) described initially by Leao (1944a) is a multifactorial event affecting the electrical, ionic, metabolic and hemodynamic activities in the brain (Vyskocil et al., 1972; Mayevsky et al., 1974; Bures et al. 1974; Mayevsky and Weiss, 1991). Due to disturbances in the ion homeostasis, the Na⁺K⁺-ATPase activity and energy metabolism are stimulated in order to restore the normal extracellular ion levels (Mayevsky et al., 1974; Hansen, 1985; Mayevsky and Weiss, 1991). The hemodynamic response to SD was a challenge to many investigators since the initial observation of dilation of pial vessels (Leao, 1944b). He concluded that the vascular responses are secondary to the local changes in the activity of neural elements. The changes in cerebral blood flow (CBF) just before, during and after the depolarization wave of SD were described by various investigators (Van Harreveld and Stamm, 1952; Van Harreveld and Ochs, 1957; Burevsova, 1957; Hansen et al., 1980; Lauritzen et al., 1982; Mies and Paschen, 1984; Lauritzen, 1984; Lauritzen and Diemer, 1986) and have been reviewed by Lauritzen (1987a,b). In all studies, a large increase in cerebral blood flow was recorded during the wave. Lauritzen and collaborators descried a post-spreading depression wave hypoperfusion, while a preceding vasoconstriction (immediately before the wave) was not established or proved. The mechanism behind the changes in CBF due to the SD wave is not clear although recently nitric oxide NO was proposed to be involved (Goadsby et al., 1992; Duckrow 1993). NO was suggested as an important factor in CBF regulation (Beckman et al., 1991; Iadecola et al., 1994; Irikura et al.,1994) as well as having direct effects on neuronal elements (Culotta and Koshland 1992; Mayer et al., 1992). In order to