Previous work by others has demonstrated that neocortical injury results in the induction of c‐fos proto‐oncogene both at and distal to the site of injury. However, secondary effects of focal brain injury, such as spreading depression and seizure activity, also have been shown to induce the expression of c‐fos. Thus, it is unclear whether the stimulus inducing c‐fos expression after generalized brain trauma is direct neuronal injury or associated, secondary effects of injury. In this study, we tested the hypothesis that a specific axonal disconnection would induce the expression of c‐fos proto‐oncogene in the injured neurons. The injury paradigm that was used was peripheral axotomy of rodent facial motoneurons. The right facial nerve was severed distal to the stylomastoid foramen, with the left side serving as an internal control. As positive controls, in a separate group of animals, seizures were invoked using bicucullin administered intraperitoneally. At the end of postoperative survival times ranging from 30 min to 24 hr, the animals were sacrificed. For northern blot analysis using a c‐fos cDNA probe, total RNA was isolated from the dissected facial nuclear groups in the injury experiments, or whole brain and neocortex in the seizure experiments. For immunocytochemical analysis using a battery of c‐fos antibodies, the animals were perfused with paraformaldehyde and processed for routine light microscope immunocytochemistry. In the bicucullin‐injected animals, c‐fos mRNA was massively induced in whole brain in a manner proportional to the overall level of gross seizure activity. The localization of the c‐fos expression occurred primarily in neurons within the neocortex. In the axotomized facial motoneurons, no induction of c‐fos mRNA or protein was found to occur at any of the timepoints examined and no basal expression of c‐fos was observed in the uninjured motoneurons. The results suggest that the rapid induction of c‐fos proto‐oncogene product is not a specific component of the nerve cell body response to injury.
Journal of Neuroscience Research – Wiley
Published: Feb 1, 1991
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