Traumatic Brain Injury and Hippocampal Plasticity: Region‐related Changes in Neurogenesis, Neuronal Lamination and Formation of Ectopic Granule Cells.

Abstract

Traumatic Brain Injury (TBI) is associated with locomotor and cognitive deficiency as well as posttraumatic seizures and temporal lobe epilepsy. Recent studies have shown increased neurogenesis, mossy fiber sprouting and/or neuronal hyperexcitability in several animal models of TBI as well as seizure. However, little is known on whether and how neuronal migration and patterning are altered in the mature brain following TBI. In the present study we examine the effect of TBI on granule cell genesis, migration and lamination in adult rats using BrdU and doublecortin (DBX) labeling. Two weeks following a unilateral controlled cortical impact, there was a reduction of DBX labeled-cells in the dorsal blade of the granule cell layer directly under the impact region, whereas increased labeling of both BrdU and DBX was present in the remaining dentate gyrus of the lesion side, relative to contralateral gyrus and sham controls. Some DBX-labeled granule cells in the impact side lost alignment with others, forming cellular islands that extended beyond the granule cell layer and in to the molecular layer. In addition, numerous DBX-positive granule cells were found in the hippocampal hilus of the lesion side. Our data suggest that cortical impact lesions in adult rats affect the survival, migration and laminar orientation of newly generated granule cells. These anatomic malformations may contribute to neurological recovery and, conversely, to hyperexcitability that often develops following TBI. Supported by NIH 5 R01 NS041551 and SIUSOM CRC funds.