Bumetanide inhibits rapid kindling in neonatal rats.
OBJECTIVE
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.


CONCLUSIONS
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.
Mazarati
Andréy
A
Department of Pediatrics, Neurology Division, David Geffen School of Medicine at UCLA, Los Angeles, California 90095-1752, USA. mazarati@ucla.edu
Shin
Don
D
Sankar
Raman
R
D000818:Animals; D000831:Animals, Newborn; D000927:Anticonvulsants / Q000494:pharmacology; D002034:Bumetanide / Q000494:pharmacology* / Q000627:therapeutic use; D004195:Disease Models, Animal; D004558:Electric Stimulation; D019054:Evoked Potentials, Motor / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects / Q000254:growth & development / Q000503:physiopathology; D006801:Humans; D007696:Kindling, Neurologic / Q000187:drug effects* / Q000502:physiology; D008297:Male; D009431:Neural Conduction / Q000187:drug effects; D009473:Neuronal Plasticity / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D012640:Seizures / Q000139:chemically induced* / Q000503:physiopathology / Q000517:prevention & control*; D049994:Sodium Potassium Chloride Symporter Inhibitors; D028021:Sodium-Potassium-Chloride Symporters / Q000494:pharmacology*
D000927:Anticonvulsants; D049994:Sodium Potassium Chloride Symporter Inhibitors; D028021:Sodium-Potassium-Chloride Symporters; D002034:Bumetanide