The effects of octanol on penicillin induced epileptiform activity in rats: An in vivo study
ABSTRACT The common features of all types of epilepsy are the synchronized and uncontrolled discharges of nerve cell assemblies. The reason for the pathologically synchronized discharges of the neuron is not exactly known yet. Recent reports claim that gap junctions have a critical role in neuronal synchronization. The present study was planned to investigate the effects of octanol, a gap junction blocker, on penicillin-induced experimental epilepsy. Permanent screw electrodes allowing EEG monitoring from conscious animals and permanent cannula providing the administration of the substances to the brain ventricle were placed into the cranium of rats under general anesthesia. After the postoperative recovery period, epileptiform activity was generated by injecting 300 IU crystallized penicillin through the ventricular cannula. When epileptiform activity, monitored from a digital recording system, reached at its maximum intensity, octanol was applied in the same way as penicillin administered. Application of octanol caused an inhibition in the epileptiform activity. Vehicle solution alone did not affect the epileptiform activity. Results of this study suggest that the blockade of electrical synapses may contribute to the prevention and amelioration of epileptic activity. Production of gap junction blockers selective for connexin types is needed. Further studies on the differential roles of gap junctions on certain epileptiform activities are required.
- SourceAvailable from: Gregory M Jacobson
[Show abstract] [Hide abstract]
- "In vivo seizure models, where cell-to-cell communication via gap junctions is manipulated before the administration of proconvulsant drugs, have suggested roles for gap junctional intercellular communication in ictogenesis acting via axonal excitatoryexcitatory gap junctions (Traub, et al. 2002). Gap junction blockade with both octanol and carbenoxolone has been shown to be protective against penicillin-induced ictogenesis in an in vivo rat seizure model (Bostanci and Bagirici 2006). Using a pentylenetetrazol (PTZ) seizure model, Nassiri-Asl and co-workers found that Cx36 gap junction blockade with quinine increased seizure latency and decreased seizure severity. "
ABSTRACT: Large-scale synchronous firing of neurons during seizures is modulated by electrotonic coupling between neurons via gap junctions. To explore roles for connexin36 (Cx36) gap junctions in seizures, we examined the seizure threshold of connexin36 knockout (Cx36KO) mice using a pentylenetetrazol (PTZ) model. Mice (2-3months old) with Cx36 wildtype (WT) or Cx36KO genotype were treated with vehicle or 10-40mg/kg of the convulsant PTZ by intraperitoneal injection. Seizure and seizure-like behaviors were scored by examination of video collected for 20min. Quantitative real-time PCR (QPCR) was performed to measure potential compensatory neuronal connexin (Cx30.2, Cx37, Cx43 and Cx45), pannexin (PANX1 and PANX2) and gamma-aminobutyric acid type A (GABA(A)) receptor α1 subunit gene expression. Cx36KO animals exhibited considerably more severe seizures; 40mg/kg of PTZ caused severe generalized (≥grade III) seizures in 78% of KO, but just 5% of WT mice. A lower dose of PTZ (20mg/kg) induced grade II seizure-like behaviors in 40% KO vs. 0% of WT animals. There was no significant difference in either connexin, pannexin or GABA(A) α1 gene expression between WT and KO animals. Increased sensitivity of Cx36KO animals to PTZ-induced seizure suggests that Cx36 gap junctional communication functions as a physiological anti-convulsant mechanism, and identifies the Cx36 gap junction as a potential therapeutic target in epilepsy.Brain research 11/2010; 1360:198-204. DOI:10.1016/j.brainres.2010.09.006 · 2.83 Impact Factor
- [Show abstract] [Hide abstract]
ABSTRACT: Epilepsy is an important problem in neurological disorders. The common features of all types of epilepsy are the synchronized and uncontrolled discharges of nerve cell assemblies. Recent studies claimed that gap junctions have a critical role in epileptic neuronal events. The aim of present study is to investigate the effects of connexin36 (Cx36) channel blocker quinine on penicillin-induced experimental epilepsy. For this purpose, 4 months old male Wistar rats were used in the present study. Permanent screw electrodes allowing EEG monitoring from conscious animals and permanent cannula providing the administration of the substances to the brain ventricle were placed into the cranium of rats under general anesthesia. At the end of the postoperative recovery period, epileptiform activity was generated by injecting 300 IU crystallized penicillin through the ventricular cannula. When the epileptiform activity, monitored from a digital recording system, reached maximal frequency and amplitude, quinine (200, 400 or 1000 nmol) was administered similar to penicillin. Effects of quinine on epileptiform activity were assessed by both electrophysiological and behavioral analysis. Quinine suppressed epileptiform activity by decreasing the amplitude and frequency of epileptiform spikes and by attenuating the epileptiform behavior. The outcomes of this study suggest that the blockade of Cx36 channels may contribute to the amelioration of epileptic activity.Seizure 04/2007; 16(2):166-72. DOI:10.1016/j.seizure.2006.11.007 · 2.06 Impact Factor
- [Show abstract] [Hide abstract]
ABSTRACT: The role of gap junctional communication in the coordination of vascular behavior has been well established experimentally. The aim of this study was to investigate whether the gap junctional blockers would inhibit cerebral vasospasm after experimental subarachnoid hemorrhage (SAH). We used the double-hemorrhage model of SAH with injection of autologous arterial blood into the cisterna magna on days 1 and 2. Octanol or carbenoxolone was administered intracisternally on day 3, and repeated on days 4 and 5. Angiography was performed before (day 0) and 7 days after (day 7) SAH, and the diameter of the basilar artery was measured. Paraffin blocks of brain tissues were prepared and sectioned for hematoxylin and eosin staining for morphologic analysis. Arterial narrowing in SAH + octanol group and SAH + carbenoxolone group at day 7 was significantly less than that in SAH-only group and each SAH + vehicle group, respectively. Less morphologic changes in SAH + octanol group and SAH + carbenoxolone group were observed when compared to that in SAH-only group and each SAH + vehicle group. Western blotting showed that carbenoxolone down-regulated Cx43 protein expression in the BA, which in the SAH-only group was significantly higher than that of the normal group. Gap junction blockers attenuate the experimental cerebral vasospasm and down-regulate the increase in expression of Cx43 protein after SAH in rabbits. These data suggest that gap junctions play an important role in the development of cerebral vasospasm.Neurological Research 08/2008; 31(3):238-44. DOI:10.1179/174313208X322770 · 1.45 Impact Factor