Blood‑brain barrier dysfunction in epilepsy: Mechanisms, therapeutic strategies and future orientation (Review).

The blood‑brain barrier (BBB) is a crucial structure for maintaining homeostasis within the central nervous system, and its integrity plays a pivotal role in the onset and progression of epilepsy. Epileptic seizures can disrupt the molecular architecture of the BBB, including the loss of tight junction proteins, activation of matrix metalloproteinases and dysfunction of supporting cells. Various pathological changes, such as transmembrane transport disorders, upregulation of platelet‑derived growth factor receptor β and vascular endothelial growth factor signalling pathways, and activation of astrocytes and microglia, accompany these alterations. These modifications exacerbate the entry of toxic molecules (such as albumin) into the brain parenchyma, triggering neuroinflammation and neuronal damage, thereby establishing a vicious cycle of epilepsy, BBB disruption and recurrent epilepsy. Consequently, repairing or protecting the BBB is a novel strategy for controlling epileptic seizures and treating drug‑resistant epilepsy. Consequently, compared with current treatment approaches that primarily focus on suppressing neuronal excitability, repairing or protecting the BBB is a novel strategy for controlling epileptic seizures and treating drug‑resistant epilepsy. Drugs such as botulinum, levetiracetam and angiotensin receptor blockers show the potential for BBB protection. The development of nanomaterials can enhance drug concentrations in affected areas, thereby offering new avenues for refractory epilepsy. The present study systematically reviews the critical role of the BBB in the pathogenesis of epilepsy, untangles the complex association between BBB dysfunction and the course of the disease, aims to deepen our understanding of the molecular mechanisms underlying BBB damage, and explores new approaches for epilepsy prevention and treatment from a BBB perspective. This review provides a theoretical foundation and research direction for the development of diagnostic and treatment strategies that are safer and more effective than current standard therapies.