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

J Neurotrauma. 2000 Nov;17(11):1067-77. doi: 10.1089/neu.2000.17.1067.

Abstract

The neuroprotective potential of halothane anesthesia was investigated following unilateral electrolytic lesions to the forelimb representation area of the sensorimotor cortex (FL-SMC). Previously, it was found that the FL-SMC lesion increases substantially in size when the intact forelimb is immobilized with a plaster of paris cast for the first 7 days postlesion, which forces extreme overuse of the impaired forelimb during a time when nonlethally damaged tissue is vulnerable to behavioral demand. Initially, the purpose of this study was to investigate whether intracisternal infusion of basic fibroblast growth factor (bFGF or FGF-2), a potent neurotrophic factor that has been shown to have neuroprotective and plasticity promoting properties 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 neuroprotective 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 requiring brief, intermittent halothane anesthesia.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Brain / drug effects
  • Brain / pathology*
  • Brain Injuries / pathology*
  • Brain Injuries / physiopathology*
  • Cerebral Cortex / drug effects
  • Cerebral Cortex / pathology
  • Drug Administration Schedule
  • Fibroblast Growth Factor 2 / pharmacology*
  • Halothane / administration & dosage*
  • Halothane / pharmacology
  • Male
  • Motor Activity / drug effects
  • Motor Activity / physiology*
  • Nerve Degeneration / pathology*
  • Neuroprotective Agents / administration & dosage*
  • Neuroprotective Agents / pharmacology
  • Rats
  • Rats, Long-Evans
  • Substantia Nigra / drug effects
  • Substantia Nigra / pathology

Substances

  • Neuroprotective Agents
  • Fibroblast Growth Factor 2
  • Halothane