Avaliação da quantidade e regularidade de crises epilépticas induzidas por abrasamento elétrico da amigdala sobre a função cardiovascular em ratos com epilepsia

Abstract

Introduction: Temporal lobe epilepsy is one of the main neurological disorders, characterized by the occurrence of generalized tonic-clonic seizures (GTCS). These seizures significantly impact the quality of life of individuals with epilepsy and are the main risk factor for Sudden Unexpected Death in Epilepsy (SUDEP). Given this, it is relevant to investigate whether the randomness and number of seizures should be considered in animal models of epilepsy with nonspontaneous seizures, aiming to adjust experimental protocols. Methodology: Wistar rats with epilepsy induced by electrical amygdala kindling were used and divided into five groups: Sham (control), CR10 (10 regular seizures), CA10 (10 random seizures), CR20 (20 regular seizures), and CA20 (20 random seizures). The animals were subjected to their respective seizure protocols, accompanied by ECG and EEG recordings. After the last day of seizures, an ECG was recorded to evaluate heart rate variability (HRV). Subsequently, the animals were euthanized, and the heart and aorta were used in isolated organ protocols to assess cardiovascular function. The ventricle was collected for histological analyses, and both the ventricle and brain were analyzed for oxidative stress markers. Results: Epileptic animals exhibited ictal bradycardia followed by tachycardia, along with alterations in autonomic modulation, characterized by parasympathetic activity reduction, especially in cases with a higher number of random seizures. The group with more seizures showed a higher incidence of fibrillation, increased heart rate, and elevated coronary flow during reperfusion. Interstitial fibrosis and cardiac hypertrophy were also increased, with an interaction between seizure number and stimulation regimen; hypertrophy was more pronounced in 20 regular seizures and 10 random seizures groups. Aortic relaxation function was impaired in animals with 10 seizures, regardless of the regimen. In cardiac tissue, there was a redox imbalance, with decreased activity of the antioxidant enzyme SOD and increased oxidative damage (carbonylated protein), varying depending on the seizure regimen and number. In the hippocampus, oxidative stress markers (MDA and carbonylated protein) were elevated, and antioxidant enzymes (SOD and CAT) reduced; interestingly, a higher number of regular seizures was associated with lower MDA levels, suggesting a conditioning effect. Conclusion: Epilepsy alone significantly contributes to impaired cardiovascular function and increased oxidative stress in both the hippocampus and cardiac tissue. Although seizure randomness may exacerbate some of these changes, the predominant factors appear to be epilepsy itself and the total number of seizures. Therefore, models with regular seizures are also effective for evaluating epilepsy-related cardiovascular alterations.