Andréy Mazarati1, Don Shin, Raman Sankar. 1. Department of Pediatrics, Neurology Division, David Geffen School of Medicine at UCLA, Los Angeles, California 90095-1752, USA. mazarati@ucla.edu
Abstract
PURPOSE: To examine the effects of bumetanide, a selective blocker of Na+-K+-2Cl- cotransporter (NKCC1), on hippocampal excitability and rapid kindling in immature rats. METHODS: Studies were performed in Wistar rats of three ages: postnatal day 11 (P11, neonatal), P14 (postneonatal), and P21 (preadolescent). Bumetanide (0.2, 0.5, 2.5 mg/kg) was given intraperitoneally 20 min prior to the beginning of the studies. Hippocampal excitability was examined by measuring threshold and duration of afterdischarge, which had been elicited by electrical stimulation of ventral hippocampus. Kindling procedure consisted of 80 electrical stimulations of ventral hippocampus, delivered every 5 min. RESULTS: At P11, bumetanide (0.5 mg/kg) increased the baseline hippocampal afterdischarge threshold and shortened the afterdischarge duration. Bumetanide delayed the occurrence, and reduced the number of full motor seizures during kindling, and prevented the development of kindling-induced enhanced seizure susceptibility in a majority of animals. At P14, bumetanide (0.5 mg/kg) induced no significant antiepileptic effects, although suppression of hippocampal excitability and inhibition of kindling were observed in a subset of animals. At P21, bumetanide (0.2; 2.5 mg/kg) exerted no effects on hippocampal excitability and kindling progression. DISCUSSION: The obtained results provide further evidence that bumetanide may be beneficial for treating neonatal seizures, and that NKCC1 represents a potential target for antiepileptic interventions in the immature brain.
PURPOSE: To examine the effects of bumetanide, a selective blocker of Na+-K+-2Cl- cotransporter (NKCC1), on hippocampal excitability and rapid kindling in immature rats. METHODS: Studies were performed in Wistar rats of three ages: postnatal day 11 (P11, neonatal), P14 (postneonatal), and P21 (preadolescent). Bumetanide (0.2, 0.5, 2.5 mg/kg) was given intraperitoneally 20 min prior to the beginning of the studies. Hippocampal excitability was examined by measuring threshold and duration of afterdischarge, which had been elicited by electrical stimulation of ventral hippocampus. Kindling procedure consisted of 80 electrical stimulations of ventral hippocampus, delivered every 5 min. RESULTS: At P11, bumetanide (0.5 mg/kg) increased the baseline hippocampal afterdischarge threshold and shortened the afterdischarge duration. Bumetanide delayed the occurrence, and reduced the number of full motor seizures during kindling, and prevented the development of kindling-induced enhanced seizure susceptibility in a majority of animals. At P14, bumetanide (0.5 mg/kg) induced no significant antiepileptic effects, although suppression of hippocampal excitability and inhibition of kindling were observed in a subset of animals. At P21, bumetanide (0.2; 2.5 mg/kg) exerted no effects on hippocampal excitability and kindling progression. DISCUSSION: The obtained results provide further evidence that bumetanide may be beneficial for treating neonatal seizures, and that NKCC1 represents a potential target for antiepileptic interventions in the immature brain.
Authors: P Hannaert; M Alvarez-Guerra; D Pirot; C Nazaret; R P Garay Journal: Naunyn Schmiedebergs Arch Pharmacol Date: 2002-02-01 Impact factor: 3.000
Authors: Volodymyr I Dzhala; Kishore V Kuchibhotla; Joseph C Glykys; Kristopher T Kahle; Waldemar B Swiercz; Guoping Feng; Thomas Kuner; George J Augustine; Brian J Bacskai; Kevin J Staley Journal: J Neurosci Date: 2010-09-01 Impact factor: 6.167
Authors: Gregory L Holmes; Chengju Tian; Amanda E Hernan; Sean Flynn; Devon Camp; Jeremy Barry Journal: Neurobiol Dis Date: 2015-03-10 Impact factor: 5.996