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 neuronal death that is responsible for some of the functional deficits associated with stroke. Our working hypothesis is that ischemia results in a prompt depletion of high energy phosphate species resulting in decreased pH and glutathione levels in brain in a temporal and spatial pattern that disrupts nerve growth factor homeostasis and increases neuronal apoptosis. Here we show hemispheric depletion of active phosphate species after ischemia. Also, we observed that the striatum is an early target for oxidative stress that is followed by energy metabolic impairment and altered neurotrophin levels that were detected by noninvasive magnetic resonance imaging (MRI) measurements of cytotoxicity and conventional biochemical determinations of apoptosis, glutathione, and nerve growth factor (NGF) protein levels in a pattern distinct from that observed in the hippocampus. Furthermore, early assessment of intracellular pH by 31P-magnetic resonance spectroscopy (31P-MRS) was a predictor of later infarct development as determined by MRI. We also show that pretreatment with pharmacological doses of NGF did not have overall significant beneficial consequences on irreversible ischemia in an intraluminal unilateral irreversible model of stroke in rat brain.
Kent
T A
TA
Department of Neurology, University of Texas Medical Branch, Galveston, USA.
Quast
M
M
Taglialatela
G
G
Rea
C
C
Wei
J
J
Tao
Z
Z
Perez-Polo
J R
JR
D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000502:physiology*; D002545:Brain Ischemia / Q000139:chemically induced / Q000503:physiopathology*; D002421:Caudate Nucleus / Q000000981:diagnostic imaging; D002536:Cerebral Arteries; D053938:DNA Fragmentation; D006624:Hippocampus / Q000000981:diagnostic imaging; D008279:Magnetic Resonance Imaging; D008297:Male; D009414:Nerve Growth Factors / Q000494:pharmacology*; D011877:Radionuclide Imaging; D051381:Rats; D017207:Rats, Sprague-Dawley
D009414:Nerve Growth Factors