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

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.

Automated summary

The neurovascular unit (NVU) is a complex network involving different cells in the brain, including specialized brain endothelium, glial and mural cells, and neurons. Research suggests that dysfunction of the NVU is a common mechanism underlying late-onset seizures or epilepsy, neurological and neurodegenerative disorders associated with aging. Further studies also indicate that seizure activity may contribute to brain aging by causing regional NVU dysfunction, while cerebrovascular pathology may be linked to comorbidities. Diagnostic approaches tailored to seizure conditions in the elderly and disease-modifying strategies focusing on NVU restoration and control of inflammation are being explored. However, there are still knowledge gaps and clinical challenges in understanding seizure onset and conditions in an aging population.