Vascular development of the central nervous system and blood-brain barrier (BBB) induction are closely linked processes. The role of factors that promote endothelial sprouting and vascular leak, such as vascular endothelial growth factor A, are well described, but the factors that suppress angiogenic sprouting and their impact on the BBB are poorly understood. Here, we show that integrin αVβ8 a...

Treatment of brain tumors with chemotherapy is limited mostly because of delivery impediments related to the blood-brain barrier (BBB). For gliomas, the most common and aggressive primary brain tumor, treatment includes surgery, radiotherapy, and chemotherapy usually administered orally or intravenously. These routes do not deliver effective concentrations. To complicate matters, chemotherapy i...

The modern view of the mammalian bloodbrain barrier (BBB) has shifted from a purely anatomic concept to a more physiological and dynamic definition. Morphologically, the BBB is formed by specialized endothelial cells (ECs) lining the intraluminal portion of brain capillaries. These ECs are characterized by specialized regions of intercellular contact (tight junctions) that prevent leakage of bl...

The blood-brain barrier (BBB) restricts transport of immunoglobulin G (IgG) in the blood to brain direction. However, IgG undergoes rapid efflux in the brain to blood direction via reverse transcytosis across the BBB after direct intracerebral injection. This BBB IgG transport system has the characteristics of an Fc receptor (FcR), but there is no molecular information on the putative BBB FcR. ...

We recently reported that apolipoprotein E (ApoE)-deficient mice with a mutation in the fibrillin-1 gene (ApoE(-/-)Fbn1(C1039G+/-)) develop accelerated atherosclerosis with enhanced inflammation, atherosclerotic plaque rupture, myocardial infarction and sudden death. In the brain, fibrillin-1 functions as an attachment protein in the basement membrane, providing structural support to the blood-...

Acute phase C-reactive protein (CRP), raised in obesity and inflammation, is a main binding protein for leptin. It is assumed that CRP contributes to leptin confrontation by preventing leptin from crossing the blood-brain barrier (BBB). Here we defined how CRP cooperates with the BBB and whether it deters leptin from attainment CNS targets. CRP was constant in blood, but did not permeate the BB...

BBB is acting as a highly selective membrane that separates the circulating blood from brain fluid [1]. This barrier is formed by endothelial cells which are connected to each other at “tight” junctions that create a complete seal between them. Consequently, only lipophilic molecules are able to cross the barrier. Hydrophilic substances, in contrast, are unable to cross the lipid walls unless a...

Manganese (Mn(2+)) has limited permeability through the blood-brain barrier (BBB). Opening the BBB such that a sufficient amount of Mn(2+) enters the extracellular space is a critical step for dynamic manganese-enhanced magnetic resonance imaging (ME-MRI) experiments. The traditional BBB opening method uses intracarotid hyperosmolar stress which results in suboptimal BBB opening, and practicall...

As P-glycoprotein (Pgp) inhibition at the blood-brain barrier (BBB) after administration of a single dose of tariquidar is transient, we performed positron emission tomography (PET) scans with the Pgp substrate (R)-[(11)C]verapamil in five healthy volunteers during continuous intravenous tariquidar infusion. Total distribution volume (VT) of (R)-[(11)C]verapamil in whole-brain gray matter incre...