Fluid percussion injury

Unilateral-onset spike and wave discharges (SWDs) following fluid percussion injury (FPI) in rats have been used for nearly two decades as a model for complex partial seizures in human post-traumatic epilepsy (PTE). This study determined if SWDs with a unilateral versus bilateral cortical onset differed. In this experiment, 2-month old rats received severe FPI (3 atm) or sham surgery and were instrumented for chronic video-electrocorticography (ECoG) recording (up to 9 months). The anti-seizure drug, carbamazepine (CBZ), and the anti-absence drug, ethosuximide (ETX), were administered separately to determine if they selectively suppressed unilateral- versus bilateral-onset SWDs, respectively. SWDs did not significantly differ between FPI and sham rats on any measured parameter (wave-shape, frequency spectrum, duration, or age-related progression), including unilateral (~17%) versus bilateral (~83%) onsets. SWDs with a unilateral onset preferentially originated ipsilateral to the craniotomy in both FPI and sham rats, suggesting that the unilateral-onset SWDs were related to surgical injury and not specifically to FPI. ETX profoundly suppressed SWDs with either unilateral or bilateral onsets, and CBZ had no effect on either type of SWD. These results suggest that SWDs with either a unilateral or bilateral onset have a pharmacosensitivity similar to absence seizures and are very different from the complex partial seizures of PTE. Therefore, SWDs with a unilateral onset after FPI are not a model of the complex partial seizures that occur in PTE, and their use for finding new treatments for PTE could be counterproductive, particularly if their close similarity to normal brain oscillations is not acknowledged ¹⁾.

The rat lateral fluid-percussion injury (FPI) model has been used extensively to study posttraumatic epilepsy (PTE). Epidemiological studies have reported that the risk of PTE is higher after more severe injury. Adult, male Wistar rats subjected to different atmospheric pressures of injury during FPI showed great variability in injury severity when functional behavior was determined based on the Neurological Severity Score (NSS) assessment. When NSS was used to select rats with the most severe FPI-induced brain injury, 63% of rats experienced at least one convulsive seizure 2-5 weeks after FPI. This same cohort of rats (i.e., selected for severe TBI based on NSS) was significantly more susceptible to PTZ-induced seizures compared to sham controls. Video/EEG recordings from the second cohort of rats with severe FPI-induced injury (based on NSS) showed a similar incidence and frequency of spike-wave discharges between rats with severe TBI and sham controls. However, the rate of isolated EEG spikes was greater in rats with severe FPI-induced injury compared to sham controls. These data from the University at Buffalo, suggest that convulsive seizures can be obtained in FPI-treated rats when NSS is used as an inclusion criterion to select rats with severe injury. Furthermore, although spike-wave discharges were equally prevalent in rats with severe FPI and sham controls, spontaneous spikes were more prevalent in the rats with severe FPI ²⁾

Fluid percussion (FP) brain injury leads to immediate indiscriminate depolarization and massive potassium efflux from neurons. Using Northern blotting, we examined the post-FP expression of primary response/immediate early genes previously described as induced by depolarization in brain. RNA from ipsilateral and contralateral hippocampus was harvested from immature and adult rats 1 h following mild, moderate, or severe lateral fluid percussion injury and compared against age-matched sham animals. C-fos gene expression was used as a positive control and showed marked induction in both pups (6-25-fold with increasing severity) and adults (9.7-17.1-fold). Kinase-induced-by-depolarization-1 (KID-1) and salt-inducible kinase (SIK) gene expression was increased in adult (KID-1 1.5-1.6-fold; SIK 1.3-3.9-fold) but not developing rats. NGFI-b RNA was elevated after injury in both ages (pups 1.8-6.1-fold; adults 3.5-5-fold), in a pattern similar to that seen for c-fos. Secretogranin I (sec I) demonstrated no significant changes. Synaptotagmin IV (syt IV) was induced only following severe injury in the immature rats (1.4-fold). Our results reveal specific severity- and age-dependent patterns of hippocampal immediate early gene expression for these depolarization-induced genes following traumatic brain injury. Differential expression of these genes may be an important determinant of the distinct molecular responses of the brain to varying severities of trauma experienced at different ages ³⁾.