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Neural Engineering

Neural Engineering - Poster Session D

Poster Z18 - Differential thresholds for neurological impairment, lethality, and pathology following blast traumatic brain injury in genetically diverse mice

Friday, October 25, 2024
3:30 PM - 4:30 PM EST
Location: Exhibit Hall E, F & G

Introduction:  Blast Traumatic Brain Injury (bTBI) is a leading cause of disability and lethality in our military personnel. Despite the unique genetic makeup of our human population, genetic predisposition and resilience to bTBI remains largely unexplored. In this study, we characterized the responses following bTBI of six murine genetic strains (A/J, 129S1/SvlmJ, NOD/LtJ, NZO/HILtJ, C57BL/6J, CAst/EiJ) across a range of blast peak overpressure conditions.

Materials and

Methods:  To induce bTBI, we used a blasttube apparatus in which helium bursts through a polyethylene (PET) membrane, exposing the animal to a peak overpressure wave. PET membrane thickness correlates with peak overpressure. Each animal was anesthetized and exposed to sham conditions or a pressure wave ranging from 0 to 630 kPa. Immediately following injury, we measured apnea, dyspnea, and righting time (RT) after exposure. At time of death or 30 min post-bTBI, each animal was perfused. Brain and lungs were examined for acute gross pathological changes and preserved for further pathological analyses.

Results, Conclusions, and Discussions: The C57BL/6J strain had significantly longer normalized RTs (7.9 ± 5.1) than any other strain at a consistent blast level. Presence of respiratory symptoms across all genetic strains and blast levels varied, with the CAst/EiJs having the highest instance of immediate apnea (47.8%) and the 129S1/SvlmJs having the lowest (14.0%). Thresholds for lethality varied significantly across strains, with the CAst/EiJ (LD50 277 kPa, 95% CI [62, 344]) and A/J (LD50 375 kPa, 95% CI [346, 462]) strains being most susceptible to lethality following bTBI, and the NZO/HILtJs (LD50 555 kPa, 95% CI [480,1044]) and NOD/LtJs (LD50 568 kPa, 95% CI [516, 656]) being most resilient. The C57BL/6Js were the most susceptible to subdural hematomas in fatal cases (71.4%), while the NZO/HILtJ strain frequently showed pulmonary damage (80.0%). Total ventricular area varied across strains, but not between sham and injured animals of a given strain. These findings in combination with neurobehavioral characterization will offer insight into the relationship between genetic makeup and response to bTBI.

Acknowledgements (Optional):