Effect of Co-administration of Bumetanide and Phenobarbital on Seizure Attacks in Temporal Lobe Epilepsy

Basic and Clinical Neuroscience

ARTICLE

Rahmanzadeh, Reza¹  Mehrabi, Soraya¹  Barati, Mahmood²  Ahmadi, Milad³  Golab, Fereshteh¹  Kazmi, Sareh¹  Joghataei, Mohammad Taghi¹  Seifi, Morteza⁴  Gholipourmalekabadi, Mazaher⁵ 

[1]Cellular and Molecular Research Center, Iran University of Medical Sciences

[2]Department of Biotechnology, School of Allied Medicine, Iran University of Medical Science

[3]Shefa Neuroscience Research Center

[4]Department of Medical Genetics, Faculty of Medicine and Dentistry, University of Alberta

[5]Department of Tissue Engineering & Regenerative Medicine, School of Advanced Technologies in Medicine, Iran University of Medical Sciences

关键词: Bumetanide;    KCC2;    NKCC1;    Phenobarbital;    Temporal lobe epilepsy;   

DOI  :  10.32598/bcn.9.6.408

来源: Iran University of Medical Sciences

【 摘 要 】

Introduction: The resistance of temporal lobe epilepsy to classic drugs is thought to be due to disruption in the excitation/inhibition of this pathway. Two chloride transporters, NKCC1 and KCC2, are expressed differently for the excitatory state of Gamma-Amino Butyric Acid (GABA). The present study explored the effect of bumetanide as a selective NKCC1 inhibitor either alone or in combination with the phenobarbital in the pilocarpine model of epilepsy. Methods: An animal model of Status Epilepticus (SE) was induced with pilocarpine in Wistar male rats followed by phenobarbital and or bumetanide or saline administration for 45 days after the induction of SE by Intraperitoneal (IP) injection. The rats were monitored, their behavior was recorded, and after 24 hours they were sacrificed to study the expression of NKCC1 and KCC2 using real time PCR. Results: The data showed that the effects of a combination of bumetanide with phenobarbital on frequency rate and duration of seizure attack were more than those of the phenobarbital alone. In addition, in the bumetanide and combined treatment groups, NKCC1 expression decreased significantly, compared with untreated epileptic animals. A delayed decrement in NKCC1/KCC2 expression ratio after bumetanide application was also observed. Conclusion: The combination of bumetanide with phenobarbital increases the inhibition of SE and maximizes the potential of GABA signaling pathway, and can be considered as an effective therapeutic strategy in patients with epilepsy.

【 授权许可】

Unknown