PHYSICAL AND CHEMICAL CHARACTERIZATION OF NEUROLOGICAL INJURY IN AN AVIAN MODEL OF PRIMARY GENERALIZED EPILEPSY

Abstract

Purpose This study was undertaken to determine if the epileptic chicken phenotype exhibited unique physical and chemical neurological changes. Methods Quantitative 1H-MRI/MRS measurements were performed on adult control (Rr) and epileptic (rr) chickens. The metrics included nuclear relaxation rate, diffusion rate and concentration of metabolites associated with neuronal cells. Comparisons were performed using Students t or Mann-Whitney tests according to the data distribution. Results Proton density measurements detected no significant difference in density among the cerebral hemispheres and optic lobes within the control and epi birds, nor between bird phenotypes. Thus, within experimental error it appears that brain tissue density is similar in adult control and epi birds. Volume calculation from images spanning the entire brain confirmed that a consistent feature of the epi genotype was megalencephaly. Nuclear relaxation (T2 ) values obtained for the control bird were within the normal variant range for neuronal tissue. However, T2's of the epi birds were significantly higher than that of the controls ((158 ms versus 123 ms). Similarly, in the diffusion data there was no apparent hemispheric bias. The optic lobes of the control animals exhibited an apparent diffusion coefficient significantly lower than that found for the cerebrum (Table 2). Interestingly, this differential was not apparent in the epi birds. The control birds across all regions of interest exhibited an ADC significantly less than that of the epi birds. Quantitative 1Hspectroscopy using tissue extracts collected immediately after sacrifice revealed phenotypic differences in lactate, glutamate, creatine and NAA but not GABA. A reduction in NAA was detected in the cerebrum of epi birds. This is in agreement with the generally held view that seizure activity causes loss of neurones, thus the loss of N-acetyl aspartate. HPLC data corroborated the spectroscopic NAA findings but also detected an increase in GABA concentration in the epileptic birds. Conclusion The physical changes observed are consistent with dilution of the interstitial fluid by edema or through cellular reordering within the epi brain. The concomitant reduction in excitable neuronal cells and the relative increase in GABA observed in biochemical analysis are consistent with a fundamental change in the cellular population.