Photothrombotic Infarction Triggers Multiple Episodes of Cortical Spreading Depression in Distant Brain Regions

Abstract

Summary:The purposes of this study were to determine whether cortical spreading depression occurs outside of the infarct produced by photothrombotic vascular occlu sion, and also the direction of spreading. Focal cerebral thrombotic infarction was produced by irradiating the ex posed skull of anesthetized rats with green light (560 nm) following systemic injection of rose bengal dye. At prox imal sites (-2 mm anterior to the infarct border), tran sient, severe hyperemic episodes (THEs) lasting 1-2 min were intermittently recorded. THE frequency was great est in the first hour and declined over a 3-h period. THEs were accompanied (and usually preceded) by a precipi tous rise in [K +]0 (from -3 to >40 mM) and were asso ciated with increases in local tissue oxygen tension Previous studies have defined marked differences between the consequences of severe focal and glob al cerebral ischemia. During global ischemia, elec trical, ion transport, and oxidative metabolic activ ities cease; this results in declines of creatine phos phate (PCr) and ATP, suppression of synaptic functioning, loss of transmembrane ion gradients, and accumulation of intracellular calcium ion (re view by Siesjo and Bengtsson, 1989).Following the onset of focal brain ischemia in many animal models, similar deteriorative changes ensue in the ischemic core as in tissue subjected to global ischemia (Hillered et al., 1989;Heiss et al.,

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

“…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. Previous studies demon strated that 5-10 spontaneous depolarizations could be recorded during the first few hours after the oc clusion (Gill et al, 1992;Iijima et al, 1992;Neder gaard and Hansen, 1993;Back et al, 1994;Dietrich et al, 1994). We observed transient ADC changes outside of the ischemic lesion in 3 of 12 animals with MCA occlusion (25%).…”

“…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.…”

Cortical spreading depression activates and upregulates MMP-9

“…Barrier disruption may contribute to cell death and an increase in infarct volume in compromised brain. Hence, CSD may augment MMP upregulation and vascular permeability changes in migraine, stroke, and trauma and may possibly contribute to susceptibility to cerebral hemorrhage (54,56,57).…”

Pathophysiology of Cerebral Ischemia and Brain Trauma: Similarities and Differences

“…TBI has been reported to cause depolarization similar to that observed in cerebral ischemia (Katayama et al, 1990;Rogatsky et al, 1996). Propagated or nonpropagated depressions of electrical activity commonly called cortical spreading depression (CSD) or periinfarct depolarization (PID) have been described in a variety of experimental models of focal cerebral ischemia and traumatic brain injury (Back et al, 1994;Dietrich et al, 1994a;Hansen and Lauritzen, 1984;Leao, 1944;Sunami et al, 1989;Zhang et al, 2002). Importantly, these ionic events contribute to neuronal damage in vulnerable brain regions such as the ischemic penumbra (Back et al, 1996;Busch et al, 1996;Mies et al, 1993).…”