THE EFFECT OF NOS INHIBITON ON GABA AND GLUTAMATE RELEASE IN HUMAN HIPPOCAMPAL ORGANOTYPIC SLICE CULTURES
Abstract number :
1.120
Submission category :
Year :
2003
Submission ID :
3859
Source :
www.aesnet.org
Presentation date :
12/6/2003 12:00:00 AM
Published date :
Dec 1, 2003, 06:00 AM
Authors :
Zafer Goren, Hulya Cabadak, Cigdem Ozkara, Filiz Onat, Emin B. Ozyurt, Hazan Ozyurt, Berna Terzioglu, Naz Yeni, Beki Kan Pharmacology and Clinical Pharmacology, Marmara University, School of Medicine, Istanbul, Turkey; Biophysics, Marmara University, Scho
Hippocampal sclerosis is the most common neuropathological finding of temporal lobe epilepsy (TLE) in patients refractory to pharmacotherapy. In experimental models of TLE, nitric oxide (NO) mediated attenuation of inhibiton on dentate granule cells was assumed to be a factor in the increased excitability. Alternatively, NO is regarded to be a neuroactive agent for the release of glutamate. Inhibition of NO synthase activity was also shown to prevent the seizure activity. This study aims to demonstrate the role of NO in GABA and glutamate release in human epileptic tissue.
Microdialysis probe placed between 2 organotypic hippocampal slices obtained from en bloc resection material of 6 TLE patients with hippocampal sclerosis (HS) who underwent surgery, was used to study the evoked releases of GABA and glutamate with the presence of NO synthase inhibitor, L-NAME (3 X10-6M). K+ content of artificial cerebrospinal fluid was increased to 100 mM to mimic seizures. Results of hippocampal slices that verified to be viable after staining with 2 % TTC were evaluated.
HPLC analysis of 4 patients (2M, 2F) revealed changes in evoked responses (% maximum changes in respect to basal levels) in GABA with absence of L-NAME: 743, 657, 727, 385; with L-NAME: 339, 1239, 3100, 98 and in glutamate without L-NAME : 86, 1600, 142, 3790, with L-NAME: 15, 37, 63, 169 consecutively. Their mean age at surgery was 29.7 (19-50) and seizure onset was 14.9 (1-11 yrs). Three patients had history of complex febrile seizures and secondary generalized tonic clonic seizures.
These preliminary findings indicate that L-NAME supresses the glutamate release in all and enhances GABA in 2 patients suggesting more experiments are required to clarify the effects of NO for further therapeutic strategies.
[Supported by: Grant from Eczacibasi Pharmaceutical company]