Epidural pentobarbital delivery can prevent locally induced neocortical seizures in rats: the prospect of transmeningeal pharmacotherapy for intractable focal epilepsy.
OBJECTIVE
To determine whether epidural pentobarbital (PB) delivery can prevent and/or terminate neocortical seizures induced by locally administered acetylcholine (Ach) in freely moving rats.


METHODS
Rats were implanted permanently with an epidural cup placed over the right parietal cortex with intact dura mater. Epidural screw-electrodes, secured to the cup, recorded local neocortical EEG activity. In the seizure-termination study, Ach was delivered into the epidural cup, and after the development of electrographic and behavioral seizures, the Ach solution was replaced with either PB or artificial cerebrospinal fluid (aCSF; control solution). In the seizure-prevention study, the epidural Ach delivery was preceded by a 10-min exposure of the delivery site to PB or aCSF. Raw EEG recordings, EEG power spectra, and behavioral events were analyzed.


RESULTS
Ach-induced EEG seizures associated with convulsions, which were unaffected by epidural aCSF applications, were terminated by epidurally delivered PB within 2-2.5 min. Epidural deliveries of PB before Ach applications completely prevented the development of electrographic and behavioral seizures, whereas similar deliveries of aCSF exerted no influence on the seizure-generating potential of Ach.


CONCLUSIONS
This study showed for the first time that epidural AED delivery can prevent, as well as terminate, locally induced neocortical seizures. The findings support the viability of transmeningeal pharmacotherapy for the treatment of intractable neocortical epilepsy.
Ludvig
Nandor
N
Comprehensive Epilepsy Center, Department of Neurology, New York University School of Medicine, New York 10016, USA. nandor.ludvig@med.nyu.edu
Kuzniecky
Ruben I
RI
Baptiste
Shirn L
SL
John
Jenine E
JE
von Gizycki
Hans
H
Doyle
Werner K
WK
Devinsky
Orrin
O
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D000927:Anticonvulsants / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use; D002555:Cerebrospinal Fluid / Q000502:physiology; D004195:Disease Models, Animal; D004333:Drug Administration Routes; D016503:Drug Delivery Systems / Q000295:instrumentation*; D004388:Dura Mater / Q000187:drug effects / Q000378:metabolism; D004569:Electroencephalography / Q000706:statistics & numerical data; D004828:Epilepsies, Partial / Q000188:drug therapy*; D007268:Injections, Epidural; D008297:Male; D008578:Meninges / Q000187:drug effects / Q000378:metabolism*; D019579:Neocortex / Q000187:drug effects / Q000503:physiopathology*; D010296:Parietal Lobe / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D010424:Pentobarbital / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use; D051381:Rats; D020318:Rats, Long-Evans; D012640:Seizures / Q000139:chemically induced / Q000503:physiopathology / Q000517:prevention & control*
D000927:Anticonvulsants; D010424:Pentobarbital; D000109:Acetylcholine