Status epilepticus, blood–brain barrier disruption, inflammation, and epileptogenesis

doi:10.1016/j.yebeh.2015.04.047

Epilepsy & Behavior

Volume 49, August 2015, Pages 13-16

https://doi.org/10.1016/j.yebeh.2015.04.047 Get rights and content

Highlights

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Experimentally induced status epilepticus results in persistent regional BBB disruption and inflammation.
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Subtle BBB leakage can be detected many weeks after SE using MRI using a step-down infusion protocol.
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Regional leakage of the serum protein albumin increases neuronal excitability.
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Treatment that targets the TGFβ pathway can be a promising strategy to prevent epilepsy in models of BBB disruption.
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The mTOR inhibitor rapamycin might affect epileptogenesis via targeting angiogenesis and inflammation.

Abstract

Over the last 15 years, attention has been focused on dysfunction of the cerebral vasculature and inflammation as important players in epileptogenic processes, with a specific emphasis on failure of the blood–brain barrier (BBB; Fig. 1) (Seiffert et al., 2004; Marchi et al., 2007; Oby and Janigro, 2006; van Vliet et al., 2014; Vezzani et al., 2011) [3], [4], [5], [6], [7]. Here, we discuss how the BBB is disrupted as a consequence of SE and how this BBB breakdown may be involved in epileptogenesis.

This article is part of a Special Issue entitled “Status Epilepticus”.

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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ReviewStatus epilepticus, blood–brain barrier disruption, inflammation, and epileptogenesis

Highlights

Abstract

Section snippets

Blood–brain barrier breakdown as trigger for epileptogenesis

Time course of BBB breakdown after SE in animal models

What is triggering BBB disruption and how does it contribute to epileptogenesis?

Conclusion

Acknowledgments

Lancet Neurol

Semin Cell Dev Biol

Neuroscience

Neuroscience

Epilepsy Res

Neurobiol Dis

Neuropharmacology

Neuroscience

Neurosci Lett

Neuroscience

Neurobiol Dis

Brain Res

Neuroscience

Brain Res

Pharmacol Res

Epilepsy Res

J Neurol Sci

Neuron

Trends Neurosci

Neurotherapeutics

Neurobiol Dis

Neuroimage

Mol Immunol

Neurobiol Dis

Exp Neurol

Risk of unprovoked seizure after acute symptomatic seizure: effect of status epilepticus

Ann Neurol

Lasting blood–brain barrier disruption induces epileptic focus in the rat somatosensory cortex

J Neurosci

Seizure-promoting effect of blood–brain barrier disruption

Epilepsia

The blood–brain barrier and epilepsy

Epilepsia

The role of inflammation in epilepsy

Nat Rev Neurol

Overview and introduction: the blood–brain barrier in health and disease

Epilepsia

The etiological role of blood–brain barrier dysfunction in seizure disorders

Cardiovasc Psychiatry Neurol

Long-lasting pro-ictogenic effects induced in vivo by rat brain exposure to serum albumin in the absence of concomitant pathology

Epilepsia

Blood–brain barrier leakage may lead to progression of temporal lobe epilepsy

Brain

Review
Status epilepticus, blood–brain barrier disruption, inflammation, and epileptogenesis