Plastic reorganization of hippocampal and neocortical circuitry in experimental traumatic brain injury in the immature rat

The reorganization of circuitry in the immature forebrain resulting from controlled cortical impact was examined with viral transneuronal tracing. Animals injured on postnatal day (PND) 17 and sham controls from the same litters received an intracerebral injection of a recombinant strain of pseudorabies virus (PRV) into the entorhinal cortex on PND 45. Fifty hours following injection of virus the animals were perfused and infected neurons were localized immunohistochemically with antisera specific for PRV. Prior studies have demonstrated that the PRV recombinant used in this analysis moves exclusively in the retrograde direction through synaptically linked neurons. CCI induced a necrotic loss of cortex at the site of impact and variable damage to the underlying corpus callosum and rostral (dorsal) hippocampus that was not present in sham controls. Analysis of viral transport in sham controls revealed retrograde transport of virus through hippocampal and neocortical circuitry in a pattern consistent with established patterns of connectivity and topography. Injured animals exhibited preservation of topographically organized connections in both the hippocampus and neocortex. However, the magnitude of labeling in the injured hemisphere was significantly increased relative to control animals and correlated with the magnitude of the injury. The distribution of infected neurons in the contralateral uninjured hemisphere also conformed to known connections. However differences in the involvement of the corpus callosum in the injury resulted in greater variability in the number of infected neurons among cases. These data provide novel insights into trauma induced reorganization of the developing brain and add to the experimental tools that can be used to assess the basis for functional recovery in animal models of developmental traumatic brain injury.