Engaging neuroscience to advance translational research in brain barrier biology

Abstract

Preface The delivery of many potentially therapeutic and diagnostic compounds to specific areas of the brain is restricted by brain barriers, the most well known of which are the blood-brain barrier (BBB) and the blood-cerebrospinal fluid (CSF) barrier. Recent studies have shown numerous additional roles of these barriers, including an involvement in neurodevelopment, control of cerebral blood flow, and, when barrier integrity is impaired, a contribution to the pathology of many common CNS disorders such as Alzheimer’s disease, Parkinson’s disease and stroke. Thus, many key areas of neuroscientific investigation are shared with the ‘brain barriers sciences’. However, despite this overlap there has been little crosstalk. This lack of crosstalk is of more than academic interest as our emerging understanding of the neurovascular unit (NVU), composed of local neuronal circuits, glia, pericytes and the endothelium, illustrates how the brain dynamically modulates its blood flow, metabolism, and electrophysiological regulation. A key insight is that the barriers are an essential part of the NVU and as such are influenced by all cellular elements of this unit.

Nanoparticle transport across the blood brain barrier

“…Examples include neurotransmitters such as glutamate and serotonin, but also calcium, and adrenaline. 75 Through these modulatory agents, several parameters of the BBB such as capillary diameter (and thus local blood flow), expression of specific transporters, and the tightness of TJs can be regulated (Peppiatt et al, 2006;14,27,47 ;Zlokovic, 2008). Therefore, disrupted signaling between endothelial cells, pericytes and/or astrocytes may affect the integrity of the BBB.…”

Leveraging Optogenetic-Based Neurovascular Circuit Characterization for Repair

“…This hemodynamic process relies on signaling between neurons, vascular cells, and glia, operating in homeostatic balance [12]. Together, this network is known as the neurovascular unit [13,14]. Neurological conditions that disrupt any of these neurovascular components can affect the rest of the unit, leading to a cycle of reciprocal attrition, ultimately leading to the loss of the blood-brain barrier and neuronal degeneration.…”

Gyógyszertranszporterek szerepe a központi idegrendszerben

“…A proteinszinten kimutatott transzporter fehérjék térbeli és sejtszintű lokalizációja a neurovascularis egységben BCRP = breast cancer resistance protein; GLUT1 = glucose transporter-1; LRP = low-density lipoprotein receptor-related protein; MCT = monocarboxylic acid transporter; Mrp = multidrug resistance protein; Oat = organic anion transporter; Oatp = organic anion transporting protein; P-gp = P-glycoprotein; RAGE = receptor for advanced glycation end products; RLIP76 = Ral-binding protein-1 (Neuwelt és munkatársai 2011-es [11] közleményéből a szerzők és a folyóirat engedélyével)…”

“…ÖSSZEFOGLALÓ KÖZLEMÉNY traszportereket a 3. ábra mutatja be sematikus formában [11]. Más SLC-fehérjék kulcsfontosságúak a szinapszistí-pustól függő jelátvitelben a megfelelő társuló gliális transzporterekkel együtt.…”