Abstract
BACKGROUND: A recent body of evidence has suggested regular exercise as a promising complementary therapeutic strategy in the management of epilepsy and its related cognitive impairments. OBJECTIVES: To put it to the test, our study aimed to comparatively examine the effects of physical exercise, low and high doses of levetiracetam, or the combination of both on amygdala electrical kindling-induced epilepsy in rats, as well as the consequent learning and memory impairments. METHODS: Male Wistar rats were randomly divided into ten groups (n = 7 per group) as the following: (I) Control (without kindling and exercise), (II) Lev (rats were received 54 mg/kg of levetiracetam without kindling and exercise), (III) Ex (rats were subjected to exercise without kindling), (IV) Ex-K (rats were subjected to preventive exercise before kindling), (V) K (rats were subjected to kindling without any intervention), (VI) K-Ex (rats were subjected to exercise after kindling), (VII) K-L lev (rats were received 27 mg/kg levetiracetam after kindling), (VIII) K-H lev (rats were received 54 mg/kg levetiracetam after kindling), (IX) K-Ex-L lev (subjected to exercise and receiving a low dose of levetiracetam after kindling), and (X) K-Ex-H lev (rats were subjected to exercise and receiving a high dose of levetiracetam after kindling). After the kindling procedure and interventions, the seizure parameters, including dADD, S(1)L, S(2)L, S(3)L, S(4)L, S(5)L, Max S5D, and Max ADD, were recorded, and seizure-related behavioral changes were evaluated using the MWM test. RESULTS: Our findings showed that in all therapeutic interventional groups, including Ex, L lev, H lev, and their combination (Ex-L lev and Ex-H lev), there was a substantial reduction in parameters, including seizure stages, seizure duration, and dADD. In contrast, there was a significant increase in the mean delay time or latency from electrical stimulation to the onset of stages 1, 2, and 3 of seizure (S(1)L, S(2)L, and S(3)L), and all groups were significantly different from the kindling group. Moreover, the kindling-induced spatial memory and learning deficit was remarkably ameliorated by preventive exercise, Ex, L lev, H lev, and their combination. CONCLUSION: Our study reveals that, in conjunction with levetiracetam, regular exercise can ameliorate the intensity and frequency of amygdala electrical kindling-induced epileptic seizures, as well as the consequent spatial memory and learning impairments.