Abstracts

Rationale: Fluid-percussion produces injury by forcing fluid through a craniotomy against an intact dural surface. Lateral fluid percussion injury (LFPI) is currently the most commonly used experimental model of human traumatic brain injury (TBI); and, in rats, has been shown to reproduce many of the clinical and histopathological features of human posttraumatic epilepsy (PTE), as well. To date, investigators using the LFPI model of PTE have largely induced injury using a pendulum and piston-based device to drive fluid against the dural surface. Two disadvantages of this method, however, are: (1) the necessary reliance on operator skill to position and release the pendulum in order to obtain a similar, smooth pressure pulse wave with every injury; and (2) reductions in reproducibility due to variable friction between the piston's o-rings and the cylinder. Methods: We designed a novel fluid-percussion apparatus that delivers a standardized pressure pulse of air to a standing column of fluid, forcing it against the intact dural surface. The establishment of dural access, the impact forces and the pulse duration were not changed from our usual methods and were similar to those methods used by other investigators. Results: The pressure waveforms generated by this apparatus are morphologically similar to those reported in the LFPI literature. Each waveform consisted of a smooth, rapid upstroke followed by a smooth downstroke. The curves were nearly identical in appearance across trials. The currently-used critical biological indicators of injury severity (mortality rate and, indirectly, period of post-injury apnea) were used to establish the validity of this injury method compared to historical controls. Twenty animals underwent LFPI with high severity impact forces (approximately 3.5 atm) using our apparatus. Five animals died after injury despite resuscitation (20% mortality rate, compared to 31-33% in published reports). All surviving animals took greater than five minutes to right and had measured transient apneic periods of 2 to greater than 25 seconds (similar to those reported in the literature). On gross inspection, all brains had acute subdural blood collections and cortical contusions at the injury site. Histopathological examination confirmed the presence of intraparenchymal blood acutely. Gross and histopathological inspection of severely injured brains remote from injury (4 months) showed focal volume loss and cavitation at the injury site. This method of performing LFPI was effective in inducing an experimental PTE syndrome similar to those described in the literature. Conclusions: This method of generating LFPI as a model of TBI and PTE produces similar results to historical controls using a pendulum and piston-based device in many critical aspects, including: (1) similar critical biological measures of injury severity, (2) similar gross pathology, (3) similar cell loss and eventual cortical cavitation on histology, and (4) the eventual development of PTE. In addition, this method may have distinct advantages, including less reliance on operator skill and improved reproducibility.