J Neurotrauma. 2023 Oct 26. doi: 10.1089/neu.2023.0452. Online ahead of print.
Early life stress (ELS) affects neurogenesis, cognitive performance, and increases neuroinflammation after a pediatric mild traumatic brain injury (mTBI). Previous studies have shown that ELS has minimal effects in juveniles, but it shows an age-dependent effect in adults. Hence, we aimed to evaluate if ELS affects cognitive performance, hippocampal microglial activation, and neurogenesis after a mTBI in adult male rats. Maternal separation for 180 min per day (MS180) during the first 21 post-natal (P) days was used as an ELS model, while controls (CONT) remained undisturbed. At P110 the rats were subjected to a mild controlled cortical impact (2.6 mm) or sham injury. Cognition was evaluated in the Morris water maze (MWM) 14 days after injury and both hippocampal microglial activation and neurogenesis were quantified 24 h after the last day of behavioral testing. The results indicate that MS180 + mTBI, but not CONT + mTBI, rats show cognitive deficiencies in the MWM. mTBI equally increased hilus and cortical microglial activation in both groups; however, only MS180 + mTBI rats showed an increase in microglial activation in the CA1 hippocampus subfield. ELS and mTBI independently caused a decrease in hippocampal neurogenesis and this effect was not increased further in MS180 + mTBI rats. The findings demonstrate that ELS and mTBI synergistically affect cognitive performance and neuroinflammation, and suggest that ELS may cause an increase on TBI vulnerability that is only evident after mTBI.