Neurovascular unit dysfunction as a mechanism of seizures and epilepsy during aging

Erwin A. van Vliet, Nicola Marchi

Research output: Contribution to JournalReview articleAcademicpeer-review


The term neurovascular unit (NVU) describes the structural and functional liaison between specialized brain endothelium, glial and mural cells, and neurons. Within the NVU, the blood-brain barrier (BBB) is the microvascular structure regulating neuronal physiology and immune cross-talk, and its properties adapt to brain aging. Here, we analyze a research framework where NVU dysfunction, caused by acute insults or disease progression in the aging brain, represents a converging mechanism underlying late-onset seizures or epilepsy and neurological or neurodegenerative sequelae. Furthermore, seizure activity may accelerate brain aging by sustaining regional NVU dysfunction, and a cerebrovascular pathology may link seizures to comorbidities. Next, we focus on NVU diagnostic approaches that could be tailored to seizure conditions in the elderly. We also examine the impending disease-modifying strategies based on the restoration of the NVU and, more in general, the homeostatic control of anti- and pro-inflammatory players. We conclude with an outlook on current pre-clinical knowledge gaps and clinical challenges pertinent to seizure onset and conditions in an aging population.
Original languageEnglish
Pages (from-to)1297-1313
Number of pages17
Issue number6
Early online date25 Feb 2022
Publication statusPublished - Jun 2022


  • Alzheimer's disease
  • aging
  • blood-brain barrier
  • cognitive decline
  • inflammation
  • late-onset epilepsy
  • neurodegeneration
  • seizures
  • stroke
  • traumatic brain injury

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