Cortical Negative DC Deflections following Middle Cerebral Artery Occlusion and KCl-Induced Spreading Depression: Effect on Blood Flow, Tissue Oxygenation, and Electroencephalogram

Abstract

Summary: In the periphery of ischemic brain lesions, transient spreading depression-like direct current (DC) deflections occur that may be of pathophysiological im portance for determining the volume of the ischemic in farct. The effect of these deflections on cerebral blood flow, tissue oxygen tension, and electrophysiology was studied in rats submitted to intraluminal thread occlusion of the middle cerebral artery (MCA) and compared with the changes following potassium chloride (KCl)-induced spreading depression of intact animals, Immediately after MCA occlusion, cortical laser-Doppler flow (LDF) in the periphery of the MCA territory sharply decreased to 35 ± 14% of control (mean ± SD; p < 0,05), tissue P02 de clined from 28 ± 4 to 21 ± 3 mm Hg (p < 0.05), and EEG power fell to -80% of control. During 7-h occlusion, 3-11 DC deflections with a mean duration of 5.2 ± 4.8 min occurred at irregular intervals, and EEG power gradually During the last years, several laboratories have been able to show that glutamate antagonists reduce the volume of ischemic infarcts (Ozyurt et aI. , 1988; Park et aI., 1988; Dirnagl et aI., 1990). The thera peutical effect could not be attributed to increased cerebral blood flow (Park et aI., 1989; Iijima et aI., 1992), indicating that molecular mechanisms are in volved. This observation is widely held to support an excitotoxic mechanism of brain infarcts in anal ogy to glutamate toxicity in vitro (Choi, 1985) and the phenomenon of delayed neuronal death in se lectively vulnerable brain regions following a period of global ischemia (Suzuki et aI., 1983). The com-

Vasoconstrictive Neurovascular Coupling during Focal Ischemic Depolarizations

“…For example, PIDs in cats were often associated with waves of hypoperfusion; the authors observed that persistent depolarization caused a secondary regional CBF decrease in the periinfarct zone (Ohta et al, 2001). Others also occasionally observed episodic hypoperfusion during PIDs in rat cortex (Back et al, 1994). Using reflectance spectroscopy, transient, spreading episodes of increased NADH fluorescence were recorded within penumbra in cats, suggesting that PIDs reduce oxygen availability, possibly due to reduced CBF (Strong et al, 1996).…”

“…For example, indicator perfusion techniques lacked temporal resolution and, therefore, did not provide information about the dynamic CBF changes during the acute stage of focal ischemia (McColl et al, 2004;Selman et al, 1990). Similarly, episodic hypoperfusion was only occasionally observed during PIDs, probably owing to the lack of spatial resolution with laser Doppler flowmetry (Back et al, 1994;Iijima et al, 1992;Mies et al, 1994;Nallet et al, 2000;Ohta et al, 2001). In our study, we showed the adverse consequences of ischemic depolarizations on CBF using a novel real-time CBF imaging technique with high spatial and temporal resolution (12 mm/pixel, one image every 7.5 secs).…”

“…The expansion of depolarized core coincides with the occurrence of repetitive and spontaneous periinfarct spreading depolarizations (PIDs) (Hossmann, 1996). Anoxic depolarization and PIDs are associated with massive redistribution of ions across membranes, an increase in extracellular potassium ( [K + ] e ) up to 60 to 80 mmol/L, and reduction in tissue adenosine triphosphate (ATP), oxygen and pH (Back et al, 1994;Busch et al, 1996;Nedergaard and Astrup, 1986;Somjen, 2001). Therefore, it has been presumed that ischemic depolarizing events increase the metabolic burden and exacerbate the energy deficit, thereby expanding the infarct (Back et al, 1996;Selman et al, 2004).…”

Spreading Waves of a Reduced Diffusion Coefficient of Water in Normal and Ischemic Rat Brain

“…SD or SD-like depolarizations occur in the ipsi lateral cortex after MCA occlusion in rats (Gill et al, 1992;Iijima et al, 1992;Nedergaard and Hansen, 1993;Bak et al, 1994;Dietrich et al, 1994), as measured electrophysiologically. The fre quency varies with experimental conditions such as the method of the vascular occlusion, craniectomy, electrode insertion, anesthesia, brain temperature, blood glucose level, etc.…”

Investigation of feline brain anatomy for the detection of cortical spreading depression with magnetic resonance imaging

“…Such differences are important because CSD is thought to be fundamental to the development of aura in migraine (Lauritzen, 1994), and PID to underly the expansion of the focal injury in stroke and head injury (Sramka et al 1977 ;Back et al 1994 ;Hossmann, 1996 ;Mayevsky et al 1996). CSD wave propagation is associated with an ion redistribution across cell membranes in the affected regions, with a net cellular potassium efflux and corresponding sodium, chloride and calcium influx (Nicholson & Kraig, 1981).…”