Influence of hypo-osmolality and induced seizures on blood brain barrier permeability and brain concentrations of trace elements in rats

Abstract

Backgrounds: We studied the changes in blood-brain barrier (BBB) permeability and brain trace elements concentration in acute hypo-osmolality and pentylenetetrazol (PTZ)-induced seizures model in rats. Furthermore, the effect of acute hypo-osmolality on seizure activity (patterns) in the PTZ model, the correlation between seizure severity score (SS score) and changes of both of BBB permeability and brain trace elements concentration in rats were also studied. Materials and Methods: Four groups (18 animals /group) of adult male albino rats were included. The animal groups are: (1) Control group: received only a vehicle. (2) Hypo-osmolar group: received warm distilled water (DW). (3) Seizure group: injected with PTZ i.p. (4) Hypo-osmolar + seizure group: first injected with DW and then PTZ. During the next 30 minutes, the animals were observed for seizure activity. For evaluation of BBB permeability changes, serum S100B protein and Evan Blue (EB) dye content of brain tissue were evaluated. Additionally macroscopic and microscopic examinations of brain tissue were completed. Trace elements, magnesium (Mg), zinc (Zn), copper (Cu) and iron (Fe), concentration in brain tissue were estimated. Results: There were significant increase of EB content of brain tissue, and serum S100ß in hypo-osmolar, seizure and hypo-osmolar + seizure groups, as compared with control animals. These parameters were significantly increased in the hypo-osmolar + seizure group when compared with either hypo-osmolar or seizure groups. These results were confirmed by macroscopic examination of brain tissue. Trace elements concentration of brain tissue, Mg, Zn, Cu and Fe, were significantly decreased in hypo-osmolar, seizure and hypo-osmolar + seizure groups in comparison with control animals. Histological examination of sections from the hilar region of dentate gyrus of the hippocampus revealed degenerative changes in the three groups of animals in comparison with control animals. Morphometric analysis showed a significant decrease in the number of cells in the hilar region of dentate gyrus in the three groups of animals in comparison with controls. Seizure activity significantly increased in hypo-osmolar + seizure as compared to seizure group. The correlation analysis revealed that significant −ve correlations were found between SS score and trace elements concentration, while significant +ve correlations were observed between SS score, and each of EB content and serum S100ß protein in seizure and hypo-osmolar + seizure groups. Conclusion: Our study demonstrated that, hypo-osmolality and PTZ-induced seizures could result in increased BBB permeability with a decrease of brain trace elements concentration. This could play a vital role in the pathophysiology of epileptic seizures. In addition, hypo-osmolality can enhance neuronal excitability and severity of seizures in the PTZ-induced model in rats.