N-tert-butyl-alpha-phenylnitrone improves recovery of brain energy state in rats following transient focal ischemia.

Abstract

Recent results have demonstrated that the spin trapping agent N-tert-butyl-a-phenylnitrone (PBN)

Cerebral Ischemia and Reperfusion: The Pathophysiologic Concept as a Basis for Clinical Therapy

“…Although Ca 2+ changes are largely reversed in the initial reperfusion period, complete recovery may require 1 to 2 hours. When reperfusion was extended to 4 hours after 2 hours of transient focal cerebral ischemia, a deterioration of all energy metabolites (decreased ATP, phosphocreatine, acetylated energy charge and increased lactate) was seen within the previously ischemic core (Folbergrova et al, 1995), presumably associated with the progression towards irreversible cell dysfunction and death. In perifocal tissue, a comparable pattern of partial recovery during initial reperfusion with subsequent delayed deterioration was also shown, but this was again less pronounced than in the previously ischemic core.…”

A multifunctional cytoprotective agent that reduces neurodegeneration after ischemia

“…The cell death that is seen in both acute and chronic neurodegenerative diseases is complex, and depending on its physical location, a neuron may be exposed to varying levels of both ischemia and hypoxia (2,3,5,6). NMDA receptor antagonists, such as MK-801, primarily protect against ischemic cell death, whereas antioxidants, such as those found in extracts of GT, block only hypoxic cell death.…”

“…By way of example, during 2-h middle cerebral artery occlusion (MCAo) in the rat, the concentration of glucose is greatly reduced in the central core of the infarct, but only mildly in the penumbra. Restoration of glucose to a normal level occurs in both areas Ϸ1 h after reperfusion (2). Reperfusion also restores interstitial oxygen tension (pO 2 ) in the central core to its preischemic value, but penumbral pO 2 is recovered only partially (3).…”

Reactive oxygen intermediates contribute to necrotic and apoptotic neuronal injury in an infant rat model of bacterial meningitis due to group B streptococci.

“…Only recently has PBN been discovered to have a beneficial effect on oxidative injury of the CNS. PBN administration protected rats from ischemic, traumatic, and excitotoxic brain injury and reduced endotoxin induced mortality (2,7,(19)(20)(21)(22)(23)(24). PBN showed no toxicity at the dosage used and the brain concentrations have been demonstrated to be significantly higher than those in blood (25).…”