Introduction: Traumatic brain injury (TBI) sets off a complex cascade of events, which are not well understood, but can cause devastating impairments in both cognitive and sensorimotor functions. TBI rat models have been established; a mouse survival model of TBI with neurological deficits would allow use of genetic engineering tools to elucidate the fundamental processes that underlie the long-term effects of TBI. We sought to establish the level of fluid perfusion injury necessary to produce a TBI mouse model with reproducible neurological deficits, measured as sensorimotor coordination and sensorimotor reactivity.
Methods: We utilized a lateral fluid percussion injury administered through craniotomy, with dura incised. We titrated the injury (pressure wave delivered) to a level that produced consistent neurological impairment with a high frequency of survival; injury was confirmed using magnetic resonance imaging (MRI). TBI animals were compared to a sham group of animals, which underwent anesthesia and scalp incision without burrhole or fluid percussion injury. Sensorimotor coordination was tested by measuring is latency to fall on a rotating rod task, to which the animals had been acclimated prior surgery. Acoustic startle reflex was utilized to test sensorimotor function, measured as amplitude of the whole-body twitch response on a footpad, to acoustic stimuli.
Results: We established an optimal pressure of 37 PSI to deliver a consistent injury to the mouse. Rotarod scores were 228 +/- 32 in the TBI group and 290 +/- 5 (P<0.05) in the sham injury group. With regards to acoustic startle reflex TBI animals had decreased startle amplitudes overall, and furthermore showed a 65% decrease response compared to baseline versus sham animals which showed a 15% decrease compared to baseline(p<0.0001).
Conclusions: We established a model of TBI, which affected motor behavior and sensorimotor function of mice. This will provide for opportunities to study the effects of TBI in genetically engineered mice.
Patient Care: Accurate animal models allow for better carryover to humans. Potential to utilize genetically engineered mice will aid in understanding the physiology of TBI.
Learning Objectives: review traumatic brain injury models, review the aspects of TBI this model duplicates