Blood-Brain Barrier Breakdown and Blood-Brain Communication in Neurological and Psychiatric Diseases

More than a century ago, Paul Ehrlich demonstrated in a set of dye experiments the lack of permeability of intracerebral vessels to albumin-binding dyes and therefore postulated a barrier between blood and neuronal tissue. Indeed, transport across the blood-brain barrier (BBB) is tightly regulated by at least four different cells that comprise the brain microvascu-lature: the endothelial cell and highly specific tight junctions between them, the pericytes which share with the endothelial cells a common capillary basement membrane, the astrocytic foot processes which cover the capillaries, and nerve endings which innervate the vessels. Importantly, dysfunction of the BBB occurs during numerous common neurological diseases , including stroke, epilepsy, trauma, tumors, and infectious and degenerative diseases. While it has been long recognized that BBB dysfunction is associated with brain diseases, only recently it has been suggested to play a role in the pathogenesis of neuronal networks dysfunction and degener-ation. In this special issue clinical and experimental evidence for the involvement of BBB dysfunction in the pathogenesis of seizures and epilepsy (N. Marchi et al. " the etiological role of blood-brain barrier dysfunction in seizure disorders " and L. M. Gibson et al. in " Occult cerebrovascular disease and lateonset epilepsy: could loss of neurovascular unit integrity be a viable model? "), posttraumatic epilepsy (O. Tomkins et al. in " Blood-brain barrier breakdown following traumatic brain injury: a possible role in posttraumatic epilepsy "), Alzheimer's diseases (V. C. Anderson et al. in " The blood-brain barrier and microvascular water exchange in Alzheimer's disease "), and psychiatric disorders (Y. Serlin et al. in " Vascular pathology and blood-brain barrier disruption in cognitive and psychiatric complications of type 2 diabetes mellitus ") is given. Experimental evidence points to the mechanisms involved, which most importantly seems to include astroglial activation and disturbance of the extracellular milieu, specifically altered homeostasis of water and electrolytes (V. C. Anderson et al. in " The blood-brain barrier and microvascular water exchange in Alzheimer's disease "). In addition, immune response and inflammation seems to have closed bidirectional interactions with disturbed BBB permeability (H. B. Stolp et al. in " Effects of neonatal systemic inflammation on blood-brain barrier permeability and behaviour in juvenile and adult rats, " A. S. Haqqani and D. B. Stanimirovic in " Intercellular interac-tomics of human brain endothelial cells and Th17 lymphocytes: a novel strategy for identifying therapeutic targets of CNS inflammation, " and A. R. Friedman …