Effect of NGF treatment on outcome measures in a rat model of middle cerebral artery occlusion

Ischemic insults to the brain result in a time-dependent increase in neuron al death that is responsible for some of the functional deficits associated with stroke. Our working hypothesis is that ischemia results in a prompt d epletion of high energy phosphate species resulting in decreased pH and glu tathione levels in brain in a temporal and spatial pattern that disrupts ne rve growth factor homeostasis and increases neuronal apoptosis, Here we sho w hemispheric depletion of active phosphate species after ischemia, Also, w e observed that the striatum is an early target for oxidative stress that i s followed by energy metabolic impairment and altered neurotrophin levels t hat were detected by noninvasive magnetic resonance imaging (MRI) measureme nts of cytotoxicity and conventional biochemical determinations of apoptosi s, glutathione, and nerve growth factor (NGF) protein levels in a pattern d istinct from that observed in the hippocampus, Furthermore, early assessmen t of intracellular pH by P-31-magnetic resonance spectroscopy (P-31-MRS) wa s a predictor of later infarct development as determined by MRI. We also sh ow that pretreatment with pharmacological doses of NGF did not have overall significant beneficial consequences on irreversible ischemia in an intralu minal unilateral irreversible model of stroke in rat brain. J. Neurosci, Re s. 55:357-369, 1999. (C) 1999 Wiley-Liss, Inc.