Work

Repetitive blast TBI drives chronic sex-dependent paroxysmal motor behaviors and sleep disruption

Year: 2026

Type: article

Abstract: BACKGROUND: Repeated blast-induced traumatic brain injury (rbTBI) is a major cause of chronic neurological morbidity in military populations, with post-traumatic epilepsy (PTE) representing a significant long-term complication. While blast exposure is implicated in epileptogenesis and development of PTE, the direct effects of rbTBI on chronic seizure burden remains poorly understood. This study examined chronic paroxysmal motor behaviors of uncertain origin (PMBs), sleep outcomes, and neuropathology following rbTBI, incorporating sex as a biological variable. METHODS: Male and female Sprague Dawley rats underwent repeated blast exposure (~20 psi, 24-h intervals) or sham procedures using the McMillan Blast Device. Beginning 4 months post-injury, animals were housed in piezoelectric sleep/seizure monitoring cages for longitudinal assessment of spontaneous PMBs, including myoclonic jerks, wet-dog shakes, and rapid circling/running, and sleep architecture (percent sleep, total sleep, bout length, and sleep-wake transitions) over a 4-week period. At 5 months post-injury, animals were euthanized for immunohistochemical and western blot analysis of astrocytic end-feet expression (AQP4) and glial markers (GFAP, IBA1) in cortex, hippocampus, and corpus callosum. RESULTS: A high proportion of rbTBI animals (80%) developed PMBs, with males showing greater PMB prevalence, frequency, and burden than females. PMBs predominantly occurred during the dark period for both sexes after rbTBI. rbTBI produced chronic sex-specific, transient alterations in sleep architecture, with males showing increased weekly and light-period sleep alongside increased sleep consolidation (longer bout lengths, fewer transitions) from 4 to 5 months post-rbTBI. Females showed a transient reduction in weekly sleep at 4 months post-rbTBI. AQP4 expression was preserved across brain regions regardless of injury or PMB status, indicating chronic recovery of astrocytic end-feet vascular coverage after rbTBI. Hippocampal GFAP was selectively elevated in PMB-positive animals, while whole-brain GFAP protein was significantly increased in rbTBI animals overall, driven primarily by the female rbTBI group, independent of PMB burden. IBA1 expression was unaffected by injury or PMB status. CONCLUSION: rbTBI produces chronic PMBs and transient disruptions in chronic sleep architecture in male rbTBI animals. Hippocampal astrogliosis is linked to PMB in rbTBI animals and a broader increase in astrogliosis is observed in rbTBI animals, driven by the female rbTBI group. These findings demonstrate persistent sleep and astrocytic alterations alongside chronic paroxysmal motor behaviors after rbTBI, supporting a potential relationship to post-traumatic epileptogenesis.

Source: Experimental Neurology

DOI: 10.1016/j.expneurol.2026.116123