Mechanisms of spreading depression: a review of recent findings and a hypothesis

Abstract

Spreading depression of Leão (SD) can be provoked by numerous nonspecific mechanical, electrical, and chemical stimuli. A similar, if not identical, phenomenon can be provoked by hypoxia. SD is characterized by drastic depolarization of neurons, severe reduction of membrane resistance, and redistribution of ions across cell membranes. Glial cells also depolarize but retain membrane resistance. Tetraethylammonium hastens the onset of hypoxic SD but reduces the sustained potential shift and K+ outflow from cells; 4-aminopyridine also accelerates SD but has no effect on the voltage shift. N-Methyl-D-aspartate receptor antagonists delay the onset of SD, while nickel and cobalt reduce the amplitude of SD-related redistribution of Ca2+. Yet, no specific blocker of SD has been found. Microdialysis of high-K+ solution in hippocampal CA1 region induces recurrent waves of SD propagating semi-independently in adjacent tissue layers, and a prolonged unstable depressed state that has not previously been described. Neither the release of K+ ions nor of glutamate is the unique agent of SD propagation. On the basis of recent findings we propose a hypothetical sequence of events that reconcile many of the previously seemingly paradoxical observations.

Cortical Spreading Depression Protects against Subsequent Focal Cerebral Ischemia in Rats

“…In this study, a platinum wire electrode was used for DC potential measurement. This electrode may not be ideal, but the waveforms recorded were con sistent with previously reported characteristics of CSD (McLachlan, 1992;Somjen et al, 1992). CSD may be generated by insertion of the electrode itself (Verhaegen et al , 1992) and by the microdialysis probe (Tomida et al, 1989), but this would have affected both groups equally.…”

Changes in Intracellular Chloride after Oxygen–Glucose Deprivation of the Adult Hippocampal Slice: Effect of Diazepam

“…Similarly, others have shown that when neurons lose their membrane potential and undergo spreading depression-like depolarization, extracellular Cl Ϫ decreases and intracellular Cl Ϫ increases (Phillips and Nicholson 1979;Jiang et al,1992), along with a general increase in membrane permeability (Hansen 1985;Tanaka et al, 1997). This can occur during hypoxia or OGD (Somjen et al 1992;Taylor and Weber, 1993;Obeidat et al, 2000). The source of the increase in intracellular Cl Ϫ during OGD cannot be established definitively because as the membrane potential approaches zero, an inwardly directed electrochemical potential is imposed on Cl Ϫ , driving Cl Ϫ into the cell through whatever conductance is available.…”

Optical and pharmacological tools to investigate the role of mitochondria during oxidative stress and neurodegeneration

“…Maintenance of the electrochemical gradient largely depends on the Na + /K + ATP-ase activity and requires approximately 60% of the ATP produced. Therefore when energy production is impaired (e.g., during hypoxia), a rapid loss in ionic homeostasis occurs (Hansen, 1985;Müller and Somjen, 2000;Somjen et al, 1992). For example, the postsynaptic potential in hippocampal slices starts to decrease when ATP is lowered by 15% within 2 min following the initiation of hypoxia (Lipton and Whittingham, 1982).…”