Comparison of inter-injury intervals on pathological and behavioral outcomes after repeated mild blast traumatic brain injury in male and female rats

STUDY PURPOSE: The present study aims to address the gap in understanding sex differences in blood-brain barrier dysfunction following repeated mild blast-induced traumatic brain injury (rmbTBI) and to also compare acute vascular neuropathology in our rmbTBI model with 1 hour and 24 hour blast intervals. Eight-week-old male and female Sprague Dawley rats (n=6/sex/group, total n=36) were randomly assigned to three distinct injury groups: sham, rmbTBI at a 1h inter-injury interval (rmbTBI 1h), and rmbTBI at a 24h inter-injury interval (rmbTBI 24h). rmbTBI was performed using a McMillan Blast Device (open end) to induce two separate blast exposures at either 1-hour or 24-hour intervals. Compressed helium was used to produce a target 11psi (76 kPa) peak static overpressure blast wave, measured adjacent to subject body. Animal orientation was lateral with the animal body movement minimized by restraint in a mesh sling. Isoflurane was used for both injury induction and euthanasia. DATA COLLECTED: Blast parameters were collected using an AstroNova TMX-18 and analyzed using AstroView and Matlab. Quantified parameters include peak static overpressure, positve duration, peak total pressure, and psotiive impulse. Open field test was performed at 3d following the first blast exposure and elevated plus maze was performed 8d following the first blast exposure. Animals were euthanized eight days following the first blast exposure. Neuropathological outcome measures focused on blood-brain barrier and neurovascular outcomes. Isolectin, aquaporin-4, and SMI-71 were analyzed in brain, cortex, and hippocampus sections. Tight junctions, ZO-1, claudin 5, and occludin were analyzed in isolated brain capillaries. Glial markers, PDGFR-B (pericyte), IBA1 (microglia), and GFAP (astrocytes), were measured using western blot. DATA USAGE NOTES: