Effects of Anti-seizure Drugs on Motor Maps and Neurovascular Function
Date
2015-05-29
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Abstract
Seizures and epilepsy are known to alter motor map expression. Seizures also induce severe local brain hypoxia. Antiepileptics are drugs used to controls seizures in patients with epilepsy. Most of these drugs suppress seizures without preventing or reversing epileptogenesis. Therefore, they are preferably called anti-seizure drugs (ASDs). ASDs inhibit neuronal activation and/or suppress synaptic or neuromuscular transmission to control seizures. Although these drugs alter neuronal and neuromuscular function, their effects on motor maps expression have not been explored. The role of ASDs on prevention of severe seizure-induced hypoxia (SISHE) is also unknown. Moreover, a loop diuretic, bumetanide, has shown anticonvulsant activity in neonates and is currently under clinical trials for managing neonatal seizures. Anti-seizure activity of bumetanide are thought to be through reversing GABA depolarizing effect in immature neurons, by inhibiting Na+,K+ and Cl- co-transporter (NKCC1) which is the cellulullar chloride importer. Furthermore, bumetanide has recently reported to reduce seizure frequency in adult patients. Despite of these facts, study of bumetanide’s effects on motor maps expression is sparse and its role in controlling seizures in adults has not been given attention. In vivo experiments using young adult rats were carried out to determine the effects of several ASDs and bumetanide on motor maps expression. Intracortical microstimulation was done to derive the motor maps both pre- and post-drug application. Young adult rats were kindled and used to investigate the effects of bumetanide on seizure activity, which were measured 30 minutes post-bumetanide intraperitoneal treatment. Furthermore, kindling of rats was done to determine the effects of the ASDs and bumetanide on SISHE. Results showed that ASDs reduces the responsiveness of the motor cortex evidenced by forelimb map hypotrophy and elevated movement thresholds. This study has also demonstrated that bumetanide inhibits seizure activity in matured rats, which implies that anticonvulsant activity of this drug is not exclusively due to blockage of NKCC1. Further findings show that with the exception of ethosuximide which reduced the expression of SISHE, other ASDs and bumetanide neither affected brain oxygen level nor severity of SISHE.
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Keywords
Animal Physiology, Neuroscience, Pharmacology
Citation
Dika, H. I. (2015). Effects of Anti-seizure Drugs on Motor Maps and Neurovascular Function (Doctoral thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca. doi:10.11575/PRISM/25817