Abstracts

Rationale: Traumatic brain injury (TBI) is a devastating injury that involves neuroplasticity and neuroinflammation. Life-long co-morbid outcomes include increased seizure susceptibility, epilepsy, cognitive dysfunction and emotional disturbances in addition to injury-related neuromotor deficits. Interneuron loss and/or alterations have been reported at 7 days after FPI and in humans. Because dysfunction and/or loss of interneurons are involved in seizures, determining when neuroplastic changes begin to affect this population of neurons is vital to our mechanistic understanding of TBI and the post-traumatic consequences. Recent evidence further demonstrates that neuroinflammatory cascades are initiated following TBI. Inhibiting this neuroinflammation may improve functional outcomes and limit epileptic activity. We have previously shown that multiple inflammatory cytokines are elevated in the cortex 24 hours after a lateral fluid percussion injury. Considering that the hippocampus is known to be affected by TBI and is also frequently implicated in seizures, understanding the temporal sequence of inflammation and interneuron changes is important for developing more efficacious therapeutic interventions. Thus, we chose to examine neuroinflammation, glial cell activation and interneuron changes in the hipoocampus at 24 hrs after a fluid percussion injury. Methods: Male Sprague-Dawley rats (250-300g, n=12) were subjected to a lateral FPI and inflammatory mechanisms were assessed at 24 hours after injury in the hippocampus (as previously described, Mukherjee et. al 2011). Astrocytes were stained with GFAP as described previously (Arisi et al., 2011). Astrocytes were traced in 3-D using the Neurolucida program. Stereological techniques were used to count parvalbumin labeled interneurons in the pyramidal layer of CA1, CA3, as well as the hilus and granule cell layers Results: Process length, amount of process endings and amount of process bifurcations were examined. We found that at the 20 and 30 micron circles, the ipsilateral FPI rats have greater length relative to ipsilateral controls. No differences were detected in the contralateral hemisphere. . Analysis of process bifurcations revealed significantly more bifurcations in ipsilateral FPI animals within the first 10 microns from the cell body. No significant differences were found at this 24 hour time point for parvalbumin-labeled cells. Cytokine analysis revealed numerous significant differences in the ipsi- and contra-lateral hemispheres. Conclusions: The finding of numerous cytokine alterations in the hippocampus at 24 hours after FPI, indicates relatively rapid inflammation in the hippocampus following an FPI initiated in the cortex. Morphological analysis of astrocytes in the hippocampus supports this idea. Although interneurons labeled with parvalbumin are not significantly decreased at 24 hours after FPI, such cell loss is well documented at 7 days after injury. Thus, these cells have not yet died in significant numbers, indicating a possible therapeutic window.