Effect of blast exposure on the brain structure and cognition in Macaca fascicularis

Jia Lu, Kian Chye Ng, Geoffrey Ling, Jian Wu, David Jia Fei Poon, Enci Mary Kan, Mui Hong Tan, Ya Jun Wu, Ping Li, Shabbir Moochhala, Eric Yap, Lionel Kim Hock Lee, Melissa Teo, Ing Berne Yeh, Darvi Michell Bufete Sergio, Frederic Chua, Srinivasan Dinesh Kumar, Eng Ang Ling

Research output: Contribution to journalArticlepeer-review

Abstract

Blast injury to the brain is one of the major causes of death and can also significantly affect cognition and physical and psychological skills in survivors of blast. The complex mechanisms via which blast injury causes impairment of cognition and other symptoms are poorly understood. In this study, we investigated the effects of varying degrees of primary blast overpressure (BOP; 80 and 200 κPa) on the pathophysiological and magnetic resonance imaging (MRI) changes and neurocognitive performance as assessed by the monkey Cambridge Neuropsychological Test Automated Battery (mCANTAB) in non-human primates (NHP). The study aimed to examine the effects of neurobehavioral and histopathological changes in NHP. MRI and histopathology revealed ultrastructural changes in the brain, notably in the Purkinje neurons in the cerebellum and pyramidal neurons in the hippocampus, which were most vulnerable to the blast. The results correlated well with the behavioral changes and changes in motor coordination and working memory of the affected monkeys. In addition, there was white matter damage affecting myelinated axons, astrocytic hypertrophy, and increased aquaporin-4 (AQP-4) expression in astrocytes, suggesting cerebral edema. Increased apoptosis appeared to involve astrocytes and oligodendrocytes in the animals following blast exposure. The small sample size could have contributed to the non-significant outcome in cognitive performance post-blast and limited quantitative analyses. Nevertheless, the study has provided initial descriptive changes for establishing a primary BOP threshold for brain injury to serve as a useful platform for future investigations that aim to estimate brain injury potential and set safe limits of exposure.

Original languageEnglish (US)
Pages (from-to)1434-1454
Number of pages21
JournalJournal of neurotrauma
Volume29
Issue number7
DOIs
StatePublished - May 1 2012
Externally publishedYes

Keywords

  • cognitive function
  • immunohistochemistry
  • magnetic resonance imaging
  • models of injury
  • traumatic brain injury

ASJC Scopus subject areas

  • Clinical Neurology

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