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Suppressive effect of Rho-kinase inhibitors Y-27632 and fasudil on spike-and-wave discharges in genetic absence epilepsy rats from Strasbourg (GAERS)

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dc.contributor.authorONAT, FİLİZ
dc.contributor.authorsCarcak, Nihan; Yavuz, Melis; Karamahmutoglu, Tugba Eryigit; Kurt, Akif Hakan; Kucuk, Meral Urhan; Onat, Filiz Yilmaz; Buyukafsar, Kansu
dc.date.accessioned2022-03-12T22:27:06Z
dc.date.available2022-03-12T22:27:06Z
dc.date.issued2018
dc.description.abstractRho/Rho-kinase (ROCK) signaling contributes to neuroinflammation, epileptogenesis, and seizures in convulsive-type epilepsies. However, this pathway has not been investigated in absence epilepsy. We investigated RhoA activity in genetic absence epilepsy rats from Strasburg (GAERS) and the effects of ROCK inhibitors Y-27632 and fasudil on spike-and-wave discharges (SWDs) of GAERS. ROCK level and activity were measured by Western blot analysis in the brain areas involved in absence seizures (i.e., cortex and thalamus) and hippocampus. Male GAERS were stereotaxically implanted with bilateral cortical electrodes for electroencephalogram (EEG) recordings and/or guide cannula into the right ventricle. ROCK inhibitors were administered by intraperitoneal injection (1-10mg/kg for Y-27632 or fasudil) or intracerebroventricular injection (7-20nmol/5l for Y-27632 or 10-100nmol/5l for fasudil). EEG was recorded under freely moving conditions. Compared with Wistar rats, GAERS exhibited increased RhoA activity in the somatosensory cortex but not in the thalamus or hippocampus. The single systemic administration of Y-27632 and fasudil partially suppressed the duration and frequency of absence seizure, respectively. However, local brain administration caused a widespread suppressive effect on the total seizure duration, number of seizures, and the average individual seizure length. In summary, Rho/ROCK signaling may be involved in the pathophysiology of absence epilepsy. Furthermore, ROCK inhibitors can control the expression of absence seizure in GAERS, thus indicating that Y-27632 and fasudil have the potential to be used as novel anti-absence drugs.
dc.identifier.doi10.1007/s00210-018-1546-9
dc.identifier.eissn1432-1912
dc.identifier.issn0028-1298
dc.identifier.pubmed30073384
dc.identifier.urihttps://hdl.handle.net/11424/235159
dc.identifier.wosWOS:000450764500010
dc.language.isoeng
dc.publisherSPRINGER
dc.relation.ispartofNAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY
dc.rightsinfo:eu-repo/semantics/closedAccess
dc.subjectAbsence epilepsy
dc.subjectFasudil
dc.subjectGAERS
dc.subjectRho
dc.subjectRho-kinase
dc.subjectY-27632
dc.subjectKAPPA-B INHIBITION
dc.subjectROCK INHIBITOR
dc.subjectIN-VITRO
dc.subjectSOMATOSENSORY CORTEX
dc.subjectNETWORK MECHANISMS
dc.subjectCORTICAL-NEURONS
dc.subjectMODEL
dc.subjectSEIZURES
dc.subjectPROTECTS
dc.subjectINJURY
dc.titleSuppressive effect of Rho-kinase inhibitors Y-27632 and fasudil on spike-and-wave discharges in genetic absence epilepsy rats from Strasbourg (GAERS)
dc.typearticle
dspace.entity.typePublication
local.avesis.idc72adfd9-329a-45c1-99aa-c1c85d1a0c11
local.import.packageSS17
local.indexed.atWOS
local.indexed.atSCOPUS
local.indexed.atPUBMED
local.journal.numberofpages9
local.journal.quartileQ3
oaire.citation.endPage1283
oaire.citation.issue11
oaire.citation.startPage1275
oaire.citation.titleNAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY
oaire.citation.volume391
relation.isAuthorOfPublicationc359dea3-046f-4397-90d5-62e4bfc31869
relation.isAuthorOfPublication.latestForDiscoveryc359dea3-046f-4397-90d5-62e4bfc31869

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