Neural Regeneration Research ›› 2021, Vol. 16 ›› Issue (12): 2427-2428.doi: 10.4103/1673-5374.313046

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Multiple hurdle mechanism and blood-brain barrier in epilepsy: glucocorticoid receptor-heat shock proteins on drug regulation

Aneesha Achar, Chaitali Ghosh*   

  1. Cerebrovascular Research, Department of Biomedical Engineering, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA (Achar A, Ghosh C) ;Department of Biomedical Engineering and Molecular Medicine, Cleveland Clinic LernerCollege of Medicine of Case Western Reserve University, Cleveland, OH, USA (Ghosh C)
  • Online:2021-12-15 Published:2021-05-15
  • Contact: Chaitali Ghosh, PhD, GHOSHC@ccf.org.
  • Supported by:
    The present work is supported in part by the National Institute of Neurological Disorders and Stroke/National Institutes of Health grants R01NS095825 (to CG).

Abstract: Epilepsy is a complex neurologic condition which affects over 50 million people worldwide. Pharmacotherapy, primarily involving the use of anti-seizure drugs (ASDs), is an essential part of controlling seizures. However, nearly 30% of patients develop drug-resistant epilepsy, clinically defined as the persistence of seizure following trials of two ASDs (Kwan et al., 2010). Although several hypotheses have been proposed to explain this phenomenon, the mechanism of drug-resistant epilepsy still remains unclear. However, a growing body of evidence has demonstrated that blood-brain barrier (BBB) dysfunction represents an important hallmark of the epileptic brain (Salar et al., 2014; Gorter et al., 2019). As previously reported, initial brain injury or seizure may trigger disruption of the BBB, resulting in the immediate release of glutamate. Excess glutamate results in cell stress, inflammatory and cell adhesion molecule activation, and leukocyte infiltration into the brain. Finally, neuronal death, rewiring, gliosis, neurogenesis and angiogenesis, and upregulation/downregulation of receptors, transporters, and ion channels may take place within weeks to months of initial injury. These structural and functional BBB changes may trigger further risk of future seizures and anomalies (Gorter et al., 2019). Evidently, the association between drug-resistant epilepsy and impairment of the BBB function cannot be ignored.