Transient and permanent arterial occlusions modeling poststroke epilepsy in aging rats

•Permanent unilateral MCA/CCAo resulted in PTE in 4- and 12-month-old rats.•Transient unilateral MCA/CCAo resulted in PTE in only one 4-month-old animal.•Ictal 1–4 Hz spike-wave discharges accompanied inactivity or frank motor arrest.•Infarct volumes were very small and varied among age groups and o...

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Veröffentlicht in:Epilepsy research 2018-12, Vol.148, p.69-77
Hauptverfasser: Miller, Eric R., Kharlamov, Elena A., Hu, Zeyu, Klein, Edwin C., Shiau, Deng-Shan, Kelly, Kevin M.
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Sprache:eng
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Zusammenfassung:•Permanent unilateral MCA/CCAo resulted in PTE in 4- and 12-month-old rats.•Transient unilateral MCA/CCAo resulted in PTE in only one 4-month-old animal.•Ictal 1–4 Hz spike-wave discharges accompanied inactivity or frank motor arrest.•Infarct volumes were very small and varied among age groups and occlusion types.•There was severe unanticipated morbidity and mortality in 20-month-old animals. The pathophysiological mechanisms of epileptogenesis following ischemic stroke in the aged brain are not well understood, largely due to limited developments in animal modeling of poststroke epilepsy (PSE). A recent study in our laboratory (Kelly et al., 2018) using transient (3 h) unilateral middle cerebral artery (MCA) and common carotid artery (CCA) occlusion (MCA/CCAo) in 4- and 20-month-old Fischer (F344) rats resulted in epileptic seizures in both age groups; age and infarction factors independently had effects on seizure frequency. We hypothesized that permanent unilateral MCA/CCAo, a simpler model, was capable of producing results comparable to those of transient MCA/CCAo. In this study, we performed permanent MCA/CCAo and compared it to transient MCA/CCAo in 76 4-, 12-, and 20-month-old F344 rats; 41 (54%) animals experienced early, unexpected mortality. The remaining 35 (46%) animals had depth electrodes implanted. Prior to implantation of depth electrodes, 9 (26%) of these 35 animals (26%) were monitored periodically by video alone before video-EEG monitoring (17,837 h total) to assess the potential development of PSE. No EEG recordings were obtained from 12- or 20-month-old transient occlusion or 20-month-old permanent occlusion animals due to premature deaths. Five animals (14%) demonstrated epileptic seizure activity after MCA/CCAo: one 4-month-old transient occlusion animal, one 4-month-old permanent occlusion animal, and three 12-month-old permanent occlusion animals. Of these 5 animals, all but the 4-month-old permanent animal demonstrated 1–4 Hz spike-wave discharges variably associated with inactivity or frank motor arrest, and 2 animals (4- and 12-month-old permanent) demonstrated generalized ictal EEG discharges associated with grade 5 convulsive activity. All animals monitored with video-EEG demonstrated generalized 7–9 Hz spike-wave discharges, innate in F344 animals and distinct from lesion-induced epileptic seizures. Gross inspection of brains revealed variability in lesion presence and size among age groups and occlusion types. Comparison of
ISSN:0920-1211
1872-6844
DOI:10.1016/j.eplepsyres.2018.10.012