Epileptogenesis after Experimental Focal Cerebral Ischemia

Abstract

Cerebrovascular diseases are one of the most common causes of epilepsy in adults, and the incidence of stroke-induced epileptogenesis is increasing as the population ages. The mechanisms that lead to stroke-induced epileptogenesis in a subpopulation of patients, however, are still poorly understood. Recent advances in inducing epileptogenesis in rodent focal ischemia models have provided tools that can be used to identify the risk factors and neurobiologic changes leading to development of epilepsy after stroke. Here we summarize data from models in which epileptogenesis has been studied after focal ischemia; photothrombosis, middle cerebral artery (MCA) occlusion with filament, and endothelin-1-induced MCA occlusion. Analysis of the data indicates that neurobiologic changes occurring during stroke-induced epileptogenesis share some similarities to those induced by status epilepticus or traumatic brain injury.

Prevention or Modification of Epileptogenesis after Brain Insults: Experimental Approaches and Translational Research

“…The most commonly used TBI and stroke models for inducing epileptogenesis in rats are lateral fluid-percussion and controlled cortical impact for TBI and cortical photothrombosis and endothelin-1-induced occlusion of the middle cerebral artery for ischemic stroke (Karhunen et al, 2005;Pitkä nen et al, 2007a;Kharatishvili and Pitkä nen, 2010). Gene expression studies after potentially epileptogenic events such as TBI, ischemia, and SE in rats suggest that groups of functionally related genes but also several individual genes change similarly after such brain insults, and therefore might be of particular relevance for the development of epilepsy due to different etiologies (Lukasiuk et al, 2006;Pitkä nen et al, 2007a).…”

The CAVE Score for Predicting Late Seizures After Intracerebral Hemorrhage

“…4,5 Early seizures are thought to result from structural changes producing acute disruption of brain integrity, metabolic homeostasis, and transient depolarizations, whereas LS relate to neuronal reorganization and formation of epileptogenic foci. 6 Because of different predisposing factors, early seizure and LS have diversity in prognosis. 7 Several studies have examined the relationship between acute ICH and epileptic seizures with conflicting results possibly because of heterogeneous designs, inconsistent use of terminology, duration of follow-up, or differences in seizure identification and classification.…”

Ketanserin reduces the postischemic EEG and behavioural changes following Endothelin-1-induced occlusion of the middle cerebral artery in conscious rats

“…The high-amplitude delta waves are shown to be a common phenomenon of ischemic brain injury also in humans [36][37]. The injection of 60 pmol of ET adjacent to MCA did not trigger electrographic or behavioural seizures until the end of our experiment as opposite to higher dose of ET1 which may lead to non-convulsive seizure activity in EEG within 2 h after the onset of ischemia [25].…”

“…In the present study, ET1 was used as a tool to produce severe and sustained, but ultimately reversible unilateral MCA occlusion in order to provide an animal model of focal cerebral ischemia with reperfusion [14][15][16][17][18][19][20][21][22][23][24][25]. The quantitative EEG and the neurological examination both showed a substantial effect of ET1.…”

“…In this model, occlusion of the middle cerebral artery (MCAO) was induced in rats via intracerebral microinjection of Endothelin-1 (ET1) -the so-called EMCAO model. While some consequences of EMCAO on blood perfusion, behavior and histopathology have been explored in certain extent [14][15][16][17][18][19][20][21], the corresponding changes of bioelectrical activity are less investigated [22][23][24][25]. The brain electrical signals are in the list of mandatory outcome measures according to the recommendations from the first Stroke Academic Industry Roundtable meeting for the preclinical evaluation of neuroprotective and recovery enhancing drugs [26].…”