Special Feature

Cell proliferation and neuronal differentiation in the dentate gyrus in juvenile and adult rats following traumatic brain injury.

Dong Sun, MD, PhD1, Raymond J. Colello, D.Phil.2, Wilson P. Daugherty, MD, PhD1, Taek H. Kwon, MD1, Melissa J. McGinn, BA2, H. Ben Harvey, BA1, M. Ross Bullock, MD, PhD1

1 Department of Neurosurgery, 2 Department of Anatomy and Neurobiology, Medical College of Virginia, Virginia Commonwealth University, Richmond, VA 23298

Image: Immunofluorescent double-labeling of BrdU+ cells with NeuN and GFAP in the DG following TBI.

It is well known that the cognitive functions of juveniles recover to a greater extent than adult patients following traumatic brain injury (TBI). The exact mechanisms underlying this age-related disparity are unknown; however, we speculate that this improved recovery in juveniles following TBI may be associated with an endogenous neurogenic response in the hippocampus. We, therefore, examined the effects of TBI on cellular proliferation and differentiation in the dentate gyrus (DG) of the hippocampus in juvenile and adult rats following lateral fluid percussion injury (FPI). The temporal profile of the injury-induced proliferative response was determined using BrdU labeling at varying survival times.

The differentiation of these newly generated cells was investigated using cell-type specific markers. We found that, following injury, there was a significant increase in cell proliferation in the DG in both injured juveniles and adults at 2 days post injury when compared to shams. When comparing the extent of cell proliferation between juveniles and adults following TBI, the absolute number of cells generated in the subgranular zone (SGZ) was far greater in the juveniles. Moreover, the percentage of newly generated cells in the SGZ that differentiated into neurons was nearly 2 times higher in the juveniles as compared to adults. Conversely, more glial differentiation was observed in the DG of adult rats.

These findings provide compelling evidence that age-related differences in the neurogenic response to injury may underlie the differences observed in cognitive recovery in juvenile mammals as compared to adults following TBI.

This research was completed as a result of funding obtained through a CNI Option-A Research grant. For more information on this grantee, please contact CNI Program Administrator, Kristie Chamberlain, kristie.chamberlain@drs.virginia.gov or 804/662-7154.

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