Effect of Blast Exposure on the Brain Structure and Cognition inMacaca 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.

Repetitive blast exposure in mice and combat veterans causes persistent cerebellar dysfunction

“…In keeping with previous findings in both humans and blast-exposed animals (26,39,55,66,74), these data suggest that deep cerebellar white matter tracts in blast-exposed veterans may also exhibit graded vulnerability to increasing numbers of blast-related mild TBIs. The DTI tractography results (Fig.…”

“…Specifically, they found the most prominent Purkinje cell loss in the inferior/ventral aspects and, to a lesser extent, limited losses in more superior domains of the cerebellum (54). Purkinje cell damage was one of the most prominent neuropathological findings in nonhuman primates after exposure to explosive blasts that caused behavioral changes similar to humans with mild TBIs (55).…”

Self-Reported Sleep Disturbance Mediates the Relationship Between PTSD and Cognitive Outcome in Blast-Exposed OEF/OIF Veterans

“…74 It is notable that the cerebellum, known to be important for motor coordination, has been shown to be particularly vulnerable to the effects of blast. [75][76][77] It could be argued that the clinical significance of the LOC-associated reduction in manual dexterity is limited given that scores remained largely within the normal range. However, this finding is noteworthy in light of the fact that motor skills are a strong predictor of functional outcome after TBI.…”

Screening of Biochemical and Molecular Mechanisms of Secondary Injury and Repair in the Brain after Experimental Blast-Induced Traumatic Brain Injury in Rats

“…Other studies in blast TBI models have reported on axonal injury using a blast loading ranging from shock tubes to explosive blast in several species, including studies with and without head motion constraint. [3][4][5][6][7][8][9][10][11] Studies in experimental models have, however, provided few clues as to underlying pathomechanisms mediating secondary damage and/or dysfunction after blast TBI. In addition, many soldiers with post-traumatic stress disorder (PTSD) have no abnormalities on conventional brain imaging, 1,12 despite explosive blast exposure, and it has been suggested that, in some cases, pathological processes below the level of neuronal death or axonal injury, such as alterations in brain activation or cell signaling, could be important.…”