Abstract
Epilepsy is one of the most common neurological disorders which is diagnosed in around 65 million people worldwide. Clinically available antiepileptic drugs fail to control epileptic activity in about 30% of patients and they are merely symptomatic treatments and cannot cure or prevent epilepsy. There remains a need for searching new therapeutic strategies for epileptic disorders. The P2X7 receptor has been recently investigated as a new target in epilepsy treatment. Preclinical studies revealed that P2X7 receptor antagonists have anticonvulsant properties in some models of epilepsy. We aimed to investigate whether P2X7 receptor antagonist—brilliant blue G (BBG)—is able to change seizure threshold in three acute seizure models in mice, i.e., in the intravenous pentylenetetrazole seizure threshold, maximal electroshock seizure threshold and 6 Hz psychomotor seizure threshold tests. BBG was administered acutely (50–200 mg/kg, 30 min before the tests) and sub-chronically (25–100 mg/kg, once daily for seven consecutive days). Moreover, the chimney and grip strength tests were used to estimate the influence of BBG on the motor coordination and muscular strength in mice, respectively. Our results revealed only a week anticonvulsant potential of the studied P2X7 receptor antagonist because it showed anticonvulsant action only in the 6 Hz seizure test, both after acute and sub-chronic administration. BBG did not significantly influence seizure thresholds in the remaining tests. Motor coordination and muscular strength were not affected by the studied P2X7 receptor antagonist. In summary, BBG does not possess any remarkable anticonvulsant potential in acute seizure models in mice.
Highlights
Epilepsy is a common and chronic disorder experienced by about 65 million people across the globe
Purinergic receptors are widely expressed through the central nervous system both in neurons and glia cells, P2X2 and P2X4 receptors are thought to be characteristic for neurons while P2X1/5 and P2X7 receptors dominate in astrocytes
Seizure thresholds in the 6 Hz and maximal electroshock seizure threshold (MEST) tests are expressed as CS50 values with their 95% confidence limits. CS50 values were compared with the one-way analysis of variance (ANOVA) followed by the post-hoc Tukey’s test for multiple comparisons
Summary
Epilepsy is a common and chronic disorder experienced by about 65 million people across the globe. It is characterized as recurrent unprovoked seizures which are transient signs and/or symptoms of abnormal excessive and/or synchronous action of neurons in the brain [1]. Despite the fact that numerous antiepileptic drugs (AEDs) have been introduced in past decades, about one-third of affected population remains refractory to current treatment, and many others experience severe side effects such as sedation and/ or cognitive dysfunction. Several novel approaches to epilepsy treatment are investigated currently and particular attention is paid to neuron–glia interactions and purinergic signaling. P2X7 receptors, which are of interest to the present study, are involved in glia–glia and neuron–glia communication [4,5,6,7]
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