Citation

Zhang Z, Ishrat S, O'Bryan M, Klein B, Saraswati M, Robertson CL, Kannan S. J. Neurotrauma 2020; ePub(ePub): ePub.

Affiliation

Johns Hopkins School of Medicine, Department of Anesthesiology and Critical Care, Baltimore, Maryland, United States; skannan3@jhmi.edu.

Copyright

(Copyright © 2020, Mary Ann Liebert Publishers)

DOI

10.1089/neu.2019.6894

PMID

32079496

Abstract

Young children who have sustained severe traumatic brain injury (TBI) can suffer from debilitating neurocognitive deficits. Impairment of adult hippocampal neurogenesis is associated with cognitive deficits and depression. Very few studies have investigated the adult hippocampal neurogenesis after pediatric TBI. Here we evaluated long-term cognition, adult hippocampal neurogenesis, and microglial activation in a rabbit pediatric TBI model. On postnatal day 5-7 (P5-7), New Zealand white rabbits from the same litter were randomized into naïve, sham (craniotomy alone) and TBI (controlled cortical impact). Bromodeoxyuridine (BrdU, 50 mg/kg, ip) was administered at one-month post-injury, once/daily for five consecutive days. Novel object recognition and spontaneous alternation in T-maze tests were performed at 2 months post-injury to measure the cognitive functions. The animals were euthanized after behavioral tests at 3 months of age to evaluate adult hippocampal neurogenesis and microglial activation. We found that 1) Pediatric TBI caused significant deficits in hippocampal dependent cognitive functions. 2) The survival rates of adult-born neurons at both ipsilateral and contralateral hippocampus significantly decreased in the TBI group. 3) TBI induced ectopic migration of adult-born neurons at the dorsal dentate gyrus in both ipsilateral and contralateral hippocampus. 4) TBI increased astrogenesis in the hilus of the dentate gyrus. 5) TBI results in abnormal microglial activation. In conclusion, pediatric TBI causes prolonged neuroinflammation and dysregulation of the adult hippocampal neurogenesis through young adulthood, which might be responsible for the cognitive deficits. Protection of hippocampal adult neurogenesis may potentially improve outcomes.

Language: en

Keywords

ANIMAL STUDIES; COGNITIVE FUNCTION; PEDIATRIC BRAIN INJURY; TRAUMATIC BRAIN INJURY; controlled cortical impact