title: Effect of blast exposure on the brain structure and cognition in Macaca fascicularis.
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 kPa) 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.
authors.affiliation: Defence Medical and Environmental Research Institute, DSO National Laboratories, Singapore 117510. ljia@dso.org.sg
authors.forename: Jia
authors.initials: J
authors.lastname: Lu
authors.forename: Kian Chye
authors.initials: KC
authors.lastname: Ng
authors.forename: Geoffrey
authors.initials: G
authors.lastname: Ling
authors.forename: Jian
authors.initials: J
authors.lastname: Wu
authors.forename: David Jia Fei
authors.initials: DJ
authors.lastname: Poon
authors.forename: Enci Mary
authors.initials: EM
authors.lastname: Kan
authors.forename: Mui Hong
authors.initials: MH
authors.lastname: Tan
authors.forename: Ya Jun
authors.initials: YJ
authors.lastname: Wu
authors.forename: Ping
authors.initials: P
authors.lastname: Li
authors.forename: Shabbir
authors.initials: S
authors.lastname: Moochhala
authors.forename: Eric
authors.initials: E
authors.lastname: Yap
authors.forename: Lionel Kim Hock
authors.initials: LK
authors.lastname: Lee
authors.forename: Melissa
authors.initials: M
authors.lastname: Teo
authors.forename: Ing Berne
authors.initials: IB
authors.lastname: Yeh
authors.forename: Darvi Michell Bufete
authors.initials: DM
authors.lastname: Sergio
authors.forename: Frederic
authors.initials: F
authors.lastname: Chua
authors.forename: Srinivasan Dinesh
authors.initials: SD
authors.lastname: Kumar
authors.forename: Eng-Ang
authors.initials: EA
authors.lastname: Ling
mesh_terms: D000818:Animals; D001753:Blast Injuries / Q000473:pathology* / Q000503:physiopathology* / Q000523:psychology; D001921:Brain / Q000473:pathology* / Q000502:physiology / Q000503:physiopathology; D001930:Brain Injuries / Q000473:pathology* / Q000503:physiopathology* / Q000523:psychology; D003071:Cognition / Q000502:physiology*; D003072:Cognition Disorders / Q000473:pathology / Q000503:physiopathology / Q000523:psychology; D004195:Disease Models, Animal; D008252:Macaca fascicularis; D008297:Male