The Contribution of Reoxygenation to Ischemic Brain Damage

Abstract

Summary: This study examined the hypothesis that the level of postischemic reperfusion affects the severity of the resulting neuronal necrosis. In rats, tissue Po 2 % was monitored as an index of flow (reoxygenation) at four cortical sites by chronically implanted platinum elec trodes. Twenty minutes of total global cerebral ischemia was followed by 30 min of reoxygenation. The level of reoxygenation was controlled to maintain the P0 2 nearly constant at one or more of the cortical electrodes. Tissue from within 400 fLm of each of 19 electrode sites among seven rats was evaluated histologically. There was a posAn important controversy in brain ischemia re search is whether the time course of reperfusion after ischemia can influence the extent or degree of neuronal injury. It seems desirable to terminate the ischemic energy deficit and acidosis as quickly as possible. Some brain regions that develop multiple capillary occlusions during ischemia may not regain circulation ("no reflow") when the main feeding vessel is reopened unless hypertension with global hyperemia is induced. But such hyperemia may ag gravate postischemic edema. It has not been con clusively established, however, if the resulting edema contributes significantly to subsequent tis sue injury.Recent research has revealed at least three pro cesses that contribute to neuronal necrosis: opening

Delayed Treatment with MLN519 Reduces Infarction and Associated Neurologic Deficit Caused by Focal Ischemic Brain Injury in Rats via Antiinflammatory Mechanisms Involving Nuclear Factor-κB Activation, Gliosis, and Leukocyte Infiltration

“…This model closely resembles clinical stroke, which is also due to predominately acute focal ischemic attacks (Kaufmann et al, 1999;Ringelstein et al, 1992). Reperfusion has been shown to enhance injury due to production of reactive oxygen species and increased edema (Kuroiwa et al, 1988;Lipton and Rosenberg, 1994) but also allows for restoration of metabolic activity to the compromised areas (Hallenbeck and Dutka, 1990;Halsey et al, 1991). Critically, this model is well established and been shown to be highly sensitive to pharmacological intervention with neuroprotective drugs as a means to reduce the resulting brain infarction (Britton et al, 1997;Clemens and Panetta, 1994;Kawasaki-Yatsugi et al, 1998;Tatlisumak et al, 1998;Tortella et al, 1999;.…”

Early Spontaneous Improvement and Deterioration of Ischemic Stroke Patients

“…Because we did not perform TCD examinations at shorter time intervals, we do not know the exact time of recanalization, but we may argue that it was too delayed to save brain tissue. However, for 3 of these patients who had no or only limited early CT hypodensity and an extended final infarct, we cannot rule out the possibility that a reperfusion injury 24 might have supervened, thus damaging tissue that was still partially viable at hospital entry.…”

Oximetry-Guided Reoxygenation Improves Neurological Outcome After Experimental Cardiac Arrest

“…Supranormal tissue O 2 levels during reoxygenation after exposure of rat cortical brain slices to severe hypoxia are correlated with the severity of neuronal damage. 6 Gerbils treated with 100% O 2 after 15 minutes of bilateral carotid occlusion sustained increased white matter damage compared with those exposed to room air. 7 On a neurochemical level, hyperoxic reperfusion worsens the postischemic oxidized shift in tissue redox state 8 and exacerbates brain lipid as well as protein oxidation.…”