Focal brain injury, FGF-2 and the adverse effects of excessive motor demand on cortical and nigral degeneration: Marked protection by delayed intermittent exposure to halothane

The neuroprotective potential of halothane anesthesia was investigated foll owing unilateral electrolytic lesions to the forelimb representation area o f the sensorimotor cortex (FL-SMC), Previously, it was found that the FL-SM C lesion increases substantially in size when the intact forelimb is immobi lized with a plaster of paris cast for the first 7 days postlesion, which f orces extreme overuse of the impaired forelimb during a time when nonlethal ly damaged tissue is vulnerable to behavioral demand, Initially, the purpos e of this study was to investigate whether intracisternal infusion of basic fibroblast growth factor (bFGF or FGF-2), a potent neurotrophic factor tha t has been shown to have neuroprotective and plasticity promoting propertie s in focal stroke and other injury models, could prevent this use-dependent exaggeration of injury. Although intracisternal bFGF (starting 24 h after surgery, twice per week) was not found to produce significant neuroprotecti ve or behavioral effects, the brief exposure to halothane anesthesia (15-20 min) during bFGF or vehicle administration was found to prevent expansion of the lesion size, and to reduce delayed loss of neurons in the substantia nigra pars reticulata (SNr), The data have implications for investigations of the effects of neurotrophic factor in vivo, and other investigations re quiring brief, intermittent halothane anesthesia.