Neuroprotective effects of Quinpirole in lithium chloride pilocarpine-induced epilepsy in rats and its underlying mechanisms

Abstract

Abstract Epilepsy is a common neurological disorder that presents with challenging mechanisms and treatment strategies. This study investigated the neuroprotective effects of Quinpirole in lithium chloride pilocarpine-induced epileptic rats and explored its potential mechanisms. Methods: Lithium chloride pilocarpine was used to induce an epileptic model in rats, and the effects of Quinpirole on seizure symptoms and cognitive function were evaluated. The Racine scoring method, electroencephalography, and Morris water maze test were used to assess the severity of the seizures as well as learning and memory function in the group of rats with epilepsy. Additionally, immunohistochemistry and Western blot techniques were used to analyze the expression levels and morphological changes in glutamate receptor 2 (GluR2; GRIA2), BAX, and BCL2 proteins in the hippocampi of the group of rats with epilepsy. Results: First, it was confirmed that the symptoms in the group of rats with epilepsy were consistent with features of epilepsy. Furthermore, the group of rats with epilepsy demonstrated decreased learning and memory function in the Morris water maze test. Additionally, gene and protein levels of GluR2 in the hippocampi of the group of rats with epilepsy were significantly reduced. Treatment with Quinpirole significantly delayed seizure onset and decreased the mortality rate after the induction of a seizure. Furthermore, electroencephalography showed a significant decrease in the frequency of the spike waves. In the Morris water maze test, rats from the Quinpirole treatment group demonstrated a shorter latency period to reach the platform and an increased number of crossings through the target quadrant. Network pharmacology analysis revealed a close association between Quinpirole and GluR2 as well as its involvement in the cAMP signaling pathway, cocaine addiction, and dopaminergic synapses. Furthermore, immunohistochemistry and Western blot analysis showed that Quinpirole treatment resulted in a denser arrangement and a more regular morphology of the granule cells in the hippocampi of the group of rats with epilepsy. Additionally, Quinpirole treatment decreased the expression of BAX protein and increased that of BCL2 protein. Conclusion: The current study demonstrated that Quinpirole had neuroprotective effects in the epileptic rat model induced by lithium chloride pilocarpine. Further, it improved the symptoms of seizures as well as the learning and memory function of the rats and was associated with the modulation of the expression of GluR2, BAX, and BCL2 proteins. These findings provided clues that would be important for further investigation of the therapeutic potential of Quinpirole and its underlying mechanisms for epilepsy treatment.