Gabapentin and Vigabatrin Increase GABA in the Human Neocortical Slice.
Abstract number :
1.288
Submission category :
Year :
2001
Submission ID :
2995
Source :
www.aesnet.org
Presentation date :
12/1/2001 12:00:00 AM
Published date :
Dec 1, 2001, 06:00 AM
Authors :
L.D. Errante, PhD, Neurology, Yale University, New Haven, CT; A. Williamson, PhD, Neurosurgery, Yale University, New Haven, CT; D.D. Spencer, MD, Neurosurgery, Yale University, New Haven, CT; O.A. Petroff, MD, Neurology, Yale University, New Haven, CT
RATIONALE: Gabapentin rapidly increases GABA measured in the visual cortex of epilepsy patients using in vivo magnetic resonance spectroscopy (MRS). Gabapentin does not increase GABA rapidly in rodent forebrain measured using MRS. Mechanisms of action of gabapentin remain controversial. We examined the effects of gabapentin and vigabatrin (a GABA-transaminase inhibitor known to increase GABA)in a human and rat neocortical slice preparation with proton MRS.
METHODS: Human neocortical tissue was obtained from 17 patients undergoing neurosurgical resection for intractable seizures. Slices from neocortical tissue (400 [mu]m; n=15-18) were divided into 3 static chambers maintained at 34[degree]C in ACSF saturated with 95%O2/5%CO2. Each chamber was incubated for 3 hours with vigabatrin or gabapentin at 100 [mu]M or ACSF alone. Rat (n=6) neocortical slices were prepared similarly. Slices were frozen, extracted in 12% percholoric acid solution, and analyzed by high resolution proton MRS.
RESULTS: Vigabatrin significantly increased the median GABA concentration in both human and rat neocortical slices over ACSF alone by 45% (p[lt]0.001) and 70% (p[lt]0.01), respectively. Gabapentin significantly increased GABA concentrations by 15% in the human neocortical slice (p[lt]0.005). However, in the rat neocortical slice, gabapentin did not increased GABA concentration significantly.
CONCLUSIONS: This study confirms our previous studies that gabapentin increases GABA in patients with epilepsy but has minimal or no effect in a healthy rodent model. Vigabatrin increases neocortical GABA in both humans and animals. Human neocortical slice preparations will facilitate further understanding of human GABA metabolism in epilepsy.
Support: Yale University and NIH-NIND grant NS 39092.