Neurovascular unit dysfunction as a mechanism of seizures and epilepsy during aging.
Erwin Alexander van VlietNicola MarchiPublished in: Epilepsia (2022)
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.
Keyphrases
- temporal lobe epilepsy
- late onset
- resting state
- white matter
- cerebral ischemia
- oxidative stress
- functional connectivity
- healthcare
- induced apoptosis
- blood brain barrier
- spinal cord
- nitric oxide
- multiple sclerosis
- preterm infants
- liver failure
- subarachnoid hemorrhage
- spinal cord injury
- brain injury
- cell death
- middle aged
- respiratory failure
- gestational age
- preterm birth