Effect of sodium imbalance and seizure on hippocampal damage in rats.

Objectives: Hyponatremia is a frequent electrolyte disturbance that increases seizure susceptibility and may aggravate neuronal injury. Brain-derived neurotrophic factor (BDNF) is a neurotrophin critical for hippocampal function, yet the relationship between hyponatremia, seizures, and hippocampal BDNF expression remains unclear. This study aimed to investigate the effects of acute and chronic hyponatremia, with and without seizures, on hippocampal integrity in rats using immunohistochemistry and electron microscopy.

Methods: Forty-two male Wistar Albino rats were randomly assigned to six groups (n = 7/group): acute hyponatremia, acute hyponatremia + seizures, chronic hyponatremia, chronic hyponatremia + seizures, normonatremic controls, and normonatremic controls + seizures. Hyponatremia was induced by vasopressin and glucose water administration, and seizures were triggered with kainic acid. Plasma sodium levels, seizure onset/duration, BDNF expression, and ultrastructural damage were evaluated.

Results: Plasma sodium concentrations were significantly reduced in hyponatremic groups compared with controls (acute: 126.1 ± 3.8; chronic: 121.8 ± 4.3; normonatremic: 135.5 ± 2.3 mEq/L; p < 0.001). Seizures were longer and more severe in chronic hyponatremia + seizure rats compared with acute hyponatremia + seizure rats (p < 0.001). BDNF expression was significantly decreased in both acute and chronic hyponatremia groups relative to controls, with the lowest values in chronic hyponatremia + seizure rats (p < 0.05). Electron microscopy revealed marked ultrastructural injury, including myelin detachment, mitochondrial swelling, and vacuolization, most pronounced in chronic hyponatremia + seizure animals.

Conclusions: Hyponatremia, particularly in its chronic form, exacerbates seizure-induced hippocampal injury, reflected by reduced BDNF expression and severe ultrastructural damage. These findings provide novel preclinical evidence linking sodium imbalance to hippocampal vulnerability and highlight the need for further mechanistic and translational studies.