Neurovascular interactions under blood–brain barrier dysfunction

The microvascular endothelial cells in the brain, connected by tight
junctions, are surrounded by pericytes, astrocytes, microglia and
neurons. Together they act as a functional unit, named the neurovascular unit (NVU). Proper functioning of the NVU in general is
critical for normal brain functions and homeostasis. Accumulated
recent data from human and animal studies reveal that increased
permeability of the blood–brain barrier (BBB) is a major determinant in common neurological disorders. We have previously shown
that long-lasting dysfunction of the BBB leads to astrocytic transformation and epileptogenesis [1, 2, 3, 4]. Inversely, vascular injury
and specifcally BBB dysfunction are well-documented outcomes of epileptic seizures. However, the detailed endothelial pathology and
mechanisms underlying increased permeability of the BBB are poorly
understood. Here we will present recent data, directing for the role
of neuronal-enhanced glutamate release and NMDA-receptors in
seizure-induced opening of the BBB [5]. We will next describe our
recent studies on the key role of NVU interactions in the regulation
of oxygenated-blood supply to the metabolic demand of activated
brain cells (“neurovascular-coupling”). As pericytes were described to
have an important role in the integrity of the BBB, we will show that
recurrent seizures are associated with pericytic injury and BBB dysfunction, and result with impaired vascular response to seizures at
both capillary and arteriolar levels. Finally, we will discuss new data
suggesting endothelial pathology as a diagnostic and treatment target for brain disorders [6, 7].