Pediatric Traumatic Brain Injury Causes Long-Term Deficits in Adult Hippocampal Neurogenesis and Cognition

Zhi Zhang, Samiha Ishrat, Megan O'Bryan, Brandon Klein, Manda Saraswati, Courtney Robertson, Sujatha Kannan

Research output: Contribution to journalArticlepeer-review

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 Post-natal 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, intraperitoneally) was administered at 1-month post-injury, once/daily for 5 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; and 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 adult hippocampal neurogenesis may potentially improve outcomes.

Original languageEnglish (US)
Pages (from-to)1656-1667
Number of pages12
JournalJournal of neurotrauma
DOIs
StatePublished - 2020

Keywords

  • adult neurogenesis
  • cognition
  • inflammation
  • microglia
  • pediatric traumatic brain injury

ASJC Scopus subject areas

  • Clinical Neurology

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