Spreading Depression in the Brainstem of the Adult Rat: Electrophysiological Parameters and Influences on Regional Brainstem Blood Flow

Abstract

Cortical spreading depression is a pathophysiological excitation wave that occurs during pathophysiological brain conditions such as ischemic brain infarction, migraine aura, and others. Judged from experiments in rodents, the brainstem is thought to be comparatively resistant to the generation of spreading depression. However, because spreading depression can be elicited in the brainstem of rat pups after superfusing the brainstem with solutions enhancing excitability, we reinvestigated spreading depression in the brainstem of the adult rat. Based on theoretical predictions indicating a major role of extracellular potassium in susceptibility to spreading depression, we used conditioning solutions in which chloride ions were replaced by acetate and tetraethylammonium chloride and a small amount of KCI were added. Under these conditions, spreading depression was reproducibly elicited in the brainstem either by topical application of KCI crystals to the brainstem surface or by local microinjection of KCI into the brainstem. The direct current shifts so elicited were accompanied by typical elevation of extracellular potassium ions, propagated in the brainstem, and were prevented by MK-801, an N-methyl D-aspartate blocker. During spreading depression, the regional blood flow in the brainstem was transiently increased. In addition, systemic arterial blood pressure, but not the heart rate, was transiently enhanced. In the nonconditioned brainstem, KCI stimulation neither elicited spreading depression nor induced changes in regional blood flow and blood pressure. These data show that proper conditioning renders the brainstem susceptible to spreading depression, and that spreading depression at this site elicits changes in local circulation and systemic blood pressure.