ReviewStatus epilepticus, blood–brain barrier disruption, inflammation, and epileptogenesis
Section snippets
Blood–brain barrier breakdown as trigger for epileptogenesis
There is an increased risk of developing epilepsy in patients that have experienced status epilepticus (SE) (Hesdorffer et al., 1998) [1]. Excitotoxic neuronal death and reorganization of neuronal networks are considered as crucial triggers for the development of epilepsy after convulsive SE (Chen andWasterlain, 2006) [2]. Blood–brain barrier leakage is one of the earliest characteristic pathophysiological disturbances during SE and might, therefore, play an important role in the development of
Time course of BBB breakdown after SE in animal models
Research in rodent models in which BBB leakage has been visualized with markers such as Evans Blue or the serum protein albumin, respectively, has shown that BBB leakage can be detected within minutes after induction of bicuculline-induced long-lasting seizures [23]. Initial studies in various SE animal models indicated that BBB leakage can be easily detected during the first few days after pharmacologically induced SE [24], [25], [26]. However, more recently, several studies demonstrated that
What is triggering BBB disruption and how does it contribute to epileptogenesis?
There are several mechanisms and processes that cause BBB disruption soon after SE has started; each process is important at its own specific point in time during and after SE.
Conclusion
There is ample evidence that SE-induced BBB disruption and inflammation play an important role in the development of epilepsy and progression of seizure activity. Blood–brain barrier leakage is promoted by SE-associated increases of glutamate release, blood pressure rises, derailed autoregulation of cerebral blood flow, and oxidative stress and is accelerated by different pathological processes that include inflammation and angiogenesis. Early detection of these changes (e.g. by contrast
Acknowledgments
This paper is supported by the European Union Seventh Framework Programme (FP7/2007-2013) under grant agreement no. 602102 (EPITARGET).
Disclosure
The authors declare no conflicts of interest.
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