Carbamazepine modulates the spatiotemporal activity in the dentate gyrus of rats and pharmacoresistant humans in vitro.
Human hippocampal tissue resected from pharmacoresistant epilepsy patients was investigated to study the effect of the antiepileptic drug CBZ (carbamazepine) and was compared to similar experiments in the hippocampus of control rats.



The molecular layer of the DG (dentate gyrus) of human epileptic tissue and rat nonepileptic tissue was electrically stimulated and the evoked responses were recorded with voltage-sensitive dye imaging to characterize the spatiotemporal properties.



Bath applied CBZ (100 μmol/L) reduced the amplitude of the evoked responses in the human DG, albeit that no clear use-dependent effects were found at frequencies of 8 or 16 Hz. In nonepileptic control DG from rats, CBZ also reduced the amplitude of the evoked response in the molecular layer of the DG as well as the spatial extent of the response.



This study demonstrates that CBZ still reduced the activity in the DG, although the patients were clinically diagnosed as pharmacoresistant for CBZ. This suggests that in the human epileptic brain, the targets of CBZ, the voltage-gated Na(+) channels, are still sensitive to CBZ, although we used a relative high concentration and it is not possibility to assess the actual CBZ concentration that reached the target in the patient. We also concluded that the effect of CBZ was found in the activated region of the DG, quite comparable to the observations in the nonepileptic rat.
Swammerdam Institute for Life Sciences - Center for NeuroScience University of Amsterdam Amsterdam The Netherlands.
Natalie L M
NL
Cappaert
Swammerdam Institute for Life Sciences - Center for NeuroScience University of Amsterdam Amsterdam The Netherlands.
Taco R
TR
Werkman
Swammerdam Institute for Life Sciences - Center for NeuroScience University of Amsterdam Amsterdam The Netherlands.
Nuria
N
Benito
Department of Anatomy and Neuroscience Institute for Clinical and Experimental Neurosciences VU University Medical Center Amsterdam The Netherlands.
Menno P
MP
Witter
Department of Neurosurgery VU University Medical Center Amsterdam The Netherlands.
Johannes C
JC
Baayen
Swammerdam Institute for Life Sciences - Center for NeuroScience University of Amsterdam Amsterdam The Netherlands.
Wytse J
WJ
Wadman
D000293:Adolescent; D000328:Adult; D000818:Animals; D000927:Anticonvulsants / Q000008:administration & dosage / Q000494:pharmacology*; D002220:Carbamazepine / Q000008:administration & dosage / Q000494:pharmacology*; D018891:Dentate Gyrus / Q000187:drug effects* / Q000502:physiology* / Q000503:physiopathology; D000069279:Drug Resistant Epilepsy / Q000188:drug therapy* / Q000503:physiopathology; D004558:Electric Stimulation; D004833:Epilepsy, Temporal Lobe / Q000188:drug therapy* / Q000503:physiopathology; D005071:Evoked Potentials / Q000187:drug effects*; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D056969:Voltage-Sensitive Dye Imaging; D055815:Young Adult
D000927:Anticonvulsants; D002220:Carbamazepine
Antiepileptic drug; brain slices; hippocampus; temporal lobe epilepsy; voltage‐sensitive dye imaging