Compromised metabolic recovery following spontaneous spreading depression in the penumbra

Spreading depression (SD) has been demonstrated following focal ischemia, and the additional workload imposed by SD on a tissue already compromised by a marked reduction in blood flow may contribute to the evolution of irreversible damage in the ischemic penumbra. SE) was elicited in one group of rats by injecting KCl directly into a frontal craniectomy and the wave of depolarization was recorded in two craniectomies 3 and 6 mm posterior to the first one. In a second group, the middle cerebral artery was occluded using the monofilament technique and a recording electrode was placed 5 mm lateral to the midline and 0.2 mm posterior to bregma. To determine the metabolic response in the penumbral region of the cortex ipsilateral to the occlusion, brains from both groups were frozen in situ when the deflection of the SD was maximal. The spatial metabolic response of SD in the ischemic cortex was compared to that in the non-ischemic cortex. Coronal sections of the brains were lyophilized, pieces of the dorsolateral cortex were dissected and weighed, and analyzed for ATP, P-creatine, inorganic phosphate (Pi), glucose, glycogen and lactate at varying distances anterior and posterior to the recording electrode. ATP and P-creatine levels were significantly decreased at the wavefront in both groups and the levels recovered after passage of the wavefront in the normal brain, but not in the ischemic brain. Glucose and glycogen levels were significantly decreased and lactate levels significantly increased in the tissue after the passage of the wavefront. While the changes in the glucose-related metabolites persisted during recovery even in anterior portions of the cortex in both groups in the aftermath of the SD, the magnitude of the changes was greater in the penumbra than in the normal cortex. SD appears to impose an equivalent increase in energy demands in control and ischemic brain, but the ability of the penumbra to recover from the insult is compromised. Thus, increasing the energy imbalance in the penumbra after multiple SDs may hasten the deterioration of the energy status of the tissue and eventually contribute to terminal depolarization and cell death, particularly in the penumbra. (C) 2004 Elsevier B.V. All rights reserved.