Next Article in Journal
Inactivity and Skeletal Muscle Metabolism: A Vicious Cycle in Old Age
Previous Article in Journal
TGF-β/Smad3 Signalling Modulates GABA Neurotransmission: Implications in Parkinson’s Disease
Previous Article in Special Issue
Macrophage Migration Inhibitory Factor Alters Functional Properties of CA1 Hippocampal Neurons in Mouse Brain Slices
Open AccessReview

Structural, Molecular, and Functional Alterations of the Blood-Brain Barrier during Epileptogenesis and Epilepsy: A Cause, Consequence, or Both?

by Wolfgang Löscher 1,2,* and Alon Friedman 3,4
1
Department of Pharmacology, Toxicology and Pharmacy, University of Veterinary Medicine Hannover, 30559 Hannover, Germany
2
Center of Systems Neuroscience, 30559 Hannover, Germany
3
Departments of Physiology and Cell Biology, Brain and Cognitive Sciences, Zlowotski Center for Neuroscience, Ben-Gurion University of the Negev, Beer-Sheva 8410501, Israel
4
Department of Medical Neuroscience, Dalhousie University, Halifax, NS B3H 4R2, Canada
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2020, 21(2), 591; https://doi.org/10.3390/ijms21020591
Received: 25 November 2019 / Revised: 12 January 2020 / Accepted: 14 January 2020 / Published: 16 January 2020
The blood-brain barrier (BBB) is a dynamic, highly selective barrier primarily formed by endothelial cells connected by tight junctions that separate the circulating blood from the brain extracellular fluid. The endothelial cells lining the brain microvessels are under the inductive influence of neighboring cell types, including astrocytes and pericytes. In addition to the anatomical characteristics of the BBB, various specific transport systems, enzymes and receptors regulate molecular and cellular traffic across the BBB. While the intact BBB prevents many macromolecules and immune cells from entering the brain, following epileptogenic brain insults the BBB changes its properties. Among BBB alterations, albumin extravasation and diapedesis of leucocytes from blood into brain parenchyma occur, inducing or contributing to epileptogenesis. Furthermore, seizures themselves may modulate BBB functions, permitting albumin extravasation, leading to activation of astrocytes and the innate immune system, and eventually modifications of neuronal networks. BBB alterations following seizures are not necessarily associated with enhanced drug penetration into the brain. Increased expression of multidrug efflux transporters such as P-glycoprotein likely act as a ‘second line defense’ mechanism to protect the brain from toxins. A better understanding of the complex alterations in BBB structure and function following seizures and in epilepsy may lead to novel therapeutic interventions allowing the prevention and treatment of epilepsy as well as other detrimental neuro-psychiatric sequelae of brain injury. View Full-Text
Keywords: tight junctions; antiepileptic drugs; epileptogenesis; albumin; P-glycoprotein tight junctions; antiepileptic drugs; epileptogenesis; albumin; P-glycoprotein
Show Figures

Figure 1

MDPI and ACS Style

Löscher, W.; Friedman, A. Structural, Molecular, and Functional Alterations of the Blood-Brain Barrier during Epileptogenesis and Epilepsy: A Cause, Consequence, or Both? Int. J. Mol. Sci. 2020, 21, 591.

Show more citation formats Show less citations formats
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Back to TopTop