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Citation |
Lajud N, Roque A, Cheng JP, Bondi CO, Kline AE. J. Neurotrauma 2020; ePub(ePub): ePub. |
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Copyright |
(Copyright © 2020, Mary Ann Liebert Publishers) |
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DOI |
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PMID |
33040677 |
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Abstract |
Early life stress (ELS) followed by pediatric mild traumatic brain injury (mTBI) negatively impacts spatial learning and memory and increases microglial activation in adolescent rats but whether the same paradigm negatively affects higher order executive function is not known. Hence, we utilized the attentional set-shifting test (AST) to evaluate executive function (cognitive flexibility) and to determine its relationship with neuroinflammation and the hypothalamic- pituitary- adrenal (HPA) axis activity after pediatric mTBI in male rats. ELS was induced via maternal separation for 180 min per day (MS180) during the first 21 post-natal (P) days while controls (CONT) were undisturbed. At P21 fully anesthetized rats received a mild controlled cortical impact (2.2 mm tissue deformation at 4 m/s) or sham injury. AST was evaluated during adolescence on P35-40 and cytokine expression and HPA activity were analyzed on P42. The data indicate that pediatric mTBI produced a significant reversal learning deficit on the AST vs. sham (p<0.05), but the impairment was not exacerbated further by MS180. Additionally, ELS produced an overall elevation in set-loss errors on the AST and increased hippocampal IL-1β expression after TBI. A significant correlation was observed in executive dysfunction and IL-1β expression in the ipsilateral prefrontal cortex and hippocampus. Although the combination of ELS and pediatric mTBI did not worsen executive function beyond that of mTBI alone (p>0.05), it did result in increased hippocampal neuroinflammation relative to mTBI (p<0.05). These findings provide important insight into the susceptibility to incur alterations in cognitive and neuroimmune functioning after stress exposure and TBI during early life. Language: en |
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Keywords |
controlled cortical impact; INFLAMMATION; PEDIATRIC BRAIN INJURY; COGNITIVE FUNCTION |