Influence of Post-Traumatic Stress Disorder on Neuroinflammation and Cell Proliferation in a Rat Model of Traumatic Brain Injury

Georgia Health Sciences University, United States of America
PLoS ONE (Impact Factor: 3.23). 12/2013; 8(12):e81585. DOI: 10.1371/journal.pone.0081585
Source: PubMed


Long-term consequences of traumatic brain injury (TBI) are closely associated with the development of severe psychiatric disorders, such as post-traumatic stress disorder (PTSD), yet preclinical studies on pathological changes after combined TBI with PTSD are lacking. In the present in vivo study, we assessed chronic neuroinflammation, neuronal cell loss, cell proliferation and neuronal differentiation in specific brain regions of adult Sprague-Dawley male rats following controlled cortical impact model of moderate TBI with or without exposure to PTSD. Eight weeks post-TBI, stereology-based histological analyses revealed no significant differences between sham and PTSD alone treatment across all brain regions examined, whereas significant exacerbation of OX6-positive activated microglial cells in the striatum, thalamus, and cerebral peduncle, but not cerebellum, in animals that received TBI alone and combined TBI-PTSD compared with PTSD alone and sham treatment. Additional immunohistochemical results revealed a significant loss of CA3 pyramidal neurons in the hippocampus of TBI alone and TBI-PTSD compared to PTSD alone and sham treatment. Further examination of neurogenic niches revealed a significant downregulation of Ki67-positive proliferating cells, but not DCX-positive neuronally migrating cells in the neurogenic subgranular zone and subventricular zone for both TBI alone and TBI-PTSD compared to PTSD alone and sham treatment. Comparisons of levels of neuroinflammation and neurogenesis between TBI alone and TBI+PTSD revealed that PTSD did not exacerbate the neuropathological hallmarks of TBI. These results indicate a progressive deterioration of the TBI brain, which, under the conditions of the present approach, was not intensified by PTSD, at least within our time window and within the examined areas of the brain. Although the PTSD manipulation employed here did not exacerbate the pathological effects of TBI, the observed long-term inflammation and suppressed cell proliferation may evolve into more severe neurodegenerative diseases and psychiatric disorders currently being recognized in traumatized TBI patients.

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Available from: Sandra Antonieta Acosta, Dec 20, 2013
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    • "Moreover, a recent animal model of PTSD found that inflammation in the brain was associated with PTSD, and that disease progression was also associated with increased oxidative stress in the brain as well as in the periphery (Wilson et al., 2013). However, another animal model of traumatic brain injury (TBI) and PTSD found that the presence of behaviors suggestive of PTSD did not exacerbate neuroinflammation associated with TBI (Acosta et al., 2013), speaking against a robust linkage between neuroinflammation and PTSD. Further studies, potentially involving post-mortem examinations, positron emission tomography or CSF-analyses, are warranted in order to investigate whether the inflammatory response seen in PTSD stems from the brain, the periphery, or both. "
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