Rate alterable traumatic brain injury device for rodent models

Traumatic Brain Injury (TBI) is a physical impact to the head resulting in functional deficits in memory and motor systems. TBI is a prevalent problem occurring in 1.7 million people annually in the United States (Faul et al. 2010). TBIs can differ greatly in terms of the biomechanics of the impact such as magnitude, direction and rate. Indeed, it is likely that the wide range of TBI outcomes may be due to the physical characteristics of the trauma. Studies to date on impact have used injury devices with limited alterable parameters. Therefore, the existing impact studies have considered the effect of magnitude of the primary impact and have not addressed issues such as rate of pressure increase that may be important in understanding the differences in pathology associated with these impacts. In this study a novel modular computer controlled device capable of inducing controlled TBI is designed. To achieve maximum control and sensitivity, a closed loop voice coil control device is utilized, to more accurately and precisely generate the temporal force function delivered by the FPI device. This device enables generation of pressure profiles very similar to the ones generated from conventional FPI devices; in addition, different aspects of the pressure profiles such as the rate can be changed. This unique feature of this device is utilized to study the pathophysiological effects of increasing rates of pressure rise time on the rodent brain. A series of behavioral studies are conducted including neurological severity tests immediately after the injury followed by rotarod, ladder rung walk, metric and spatial information, and Morris water maze tasks between 1 to 15 days post injury. Also, the perforant path-evoked granule cell field excitability is tested. Histological characterization is performed at 4h, 24 h and 15 days post injury. The results show that a faster rate injury results in a reduced acute cell loss and improved immediate neurological outcome, but enhanced granule cell field excitability 1- week post injury. Results from immediate and chronic behavioral analysis after the injury; suggests better functional outcome in the fast injuries compared to slower injuries. However, fast injuries show a greater progressive cell loss and similar deficits in spatial information recognition as the slower rate injuries

Fluid percussion injury device for the precise control of injury parameters

BackgroundInjury to the brain can occur from a variety of physical insults and the degree of disability can greatly vary from person to person. It is likely that injury outcome is related to the biomechanical parameters of the traumatic event such as magnitude, direction and speed of the forces acting on the head.New methodTo model variations in the biomechanical injury parameters, a voice coil driven fluid percussion injury (FPI) system was designed and built to generate fluid percussion waveforms with adjustable rise times, peak pressures, and durations. Using this system, pathophysiological outcomes in the rat were investigated and compared to animals injured with the same biomechanical parameters using the pendulum based FPI system.Results in comparison with existing methodsImmediate post-injury behavior shows similar rates of seizures and mortality in adolescent rats and similar righting times, toe pinch responses and mortality rates in adult rats. Interestingly, post injury mortality in adult rats was sensitive to changes in injury rate. Fluoro-Jade labeling of degenerating neurons in the hilus and CA2-3 hippocampus were consistent between injuries produced with the voice coil and pendulum operated systems. Granule cell population spike amplitude to afferent activation, a measure of dentate network excitability, also showed consistent enhancement 1 week after injury using either system.ConclusionsOverall our results suggest that this new FPI device produces injury outcomes consistent with the commonly used pendulum FPI system and has the added capability to investigate pathophysiology associated with varying rates and durations of injury

Distinct effect of impact rise times on immediate and early neuropathology after brain injury in juvenile rats

Traumatic brain injury (TBI) can occur from physical trauma from a wide spectrum of insults ranging from explosions to falls. The biomechanics of the trauma can vary in key features, including the rate and magnitude of the insult. Although the effect of peak injury pressure on neurological outcome has been examined in the fluid percussion injury (FPI) model, it is unknown whether differences in rate of rise of the injury waveform modify cellular and physiological changes after TBI. Using a programmable FPI device, we examined juvenile rats subjected to a constant peak pressure at two rates of injury: a standard FPI rate of rise and a faster rate of rise to the same peak pressure. Immediate postinjury assessment identified fewer seizures and relatively brief loss of consciousness after fast-rise injuries than after standard-rise injuries at similar peak pressures. Compared with rats injured at standard rise, fewer silver-stained injured neuronal profiles and degenerating hilar neurons were observed 4-6 hr after fast-rise FPI. However, 1 week postinjury, both fast- and standard-rise FPI resulted in hilar cell loss and enhanced perforant path-evoked granule cell field excitability compared with sham controls. Notably, the extent of neuronal loss and increase in dentate excitability were not different between rats injured at fast and standard rates of rise to peak pressure. Our data indicate that reduced cellular damage and improved immediate neurological outcome after fast rising primary concussive injuries mask the severity of the subsequent cellular and neurophysiological pathology and may be unreliable as a predictor of prognosis

Fluid percussion injury device for the precise control of injury parameters.

BackgroundInjury to the brain can occur from a variety of physical insults and the degree of disability can greatly vary from person to person. It is likely that injury outcome is related to the biomechanical parameters of the traumatic event such as magnitude, direction and speed of the forces acting on the head.New methodTo model variations in the biomechanical injury parameters, a voice coil driven fluid percussion injury (FPI) system was designed and built to generate fluid percussion waveforms with adjustable rise times, peak pressures, and durations. Using this system, pathophysiological outcomes in the rat were investigated and compared to animals injured with the same biomechanical parameters using the pendulum based FPI system.Results in comparison with existing methodsImmediate post-injury behavior shows similar rates of seizures and mortality in adolescent rats and similar righting times, toe pinch responses and mortality rates in adult rats. Interestingly, post injury mortality in adult rats was sensitive to changes in injury rate. Fluoro-Jade labeling of degenerating neurons in the hilus and CA2-3 hippocampus were consistent between injuries produced with the voice coil and pendulum operated systems. Granule cell population spike amplitude to afferent activation, a measure of dentate network excitability, also showed consistent enhancement 1 week after injury using either system.ConclusionsOverall our results suggest that this new FPI device produces injury outcomes consistent with the commonly used pendulum FPI system and has the added capability to investigate pathophysiology associated with varying rates and durations of injury