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. 2023 Mar 11;29(5):343–353. doi: 10.1016/j.molmed.2023.02.004

Figure 1.

Figure 1

Biology of blood–brain barrier (BBB) transport.

(A) Whole-body autoradiogram of mouse euthanized after intravenous (IV) injection of radiolabeled histamine. The BBB blocks the entry of this small molecule into the brain and spinal cord (shown in white), whereas histamine is taken up by all other organs. Reproduced from [55], CC BY 4.0 license. (B) The microvasculature of the brain is visualized by this plastic cast of the human cerebellar cortex, which shows an anastomosing network of capillaries in the brain. Bar, 40 μm; arrows point to endothelial nuclei. Position of parallel arterioles is indicated by '1'. Reproduced, with permission, from [57]; copyright © 1983 Elsevier. (C) Localization of the GLUT1 glucose transporter at the luminal and abluminal membranes of the endothelium of human brain is shown by the position of the gold particles (black dots) detected by this electron microscopy immunogold study. Post-embedding immune labeling of the GLUT1 transporter is detected with a primary antibody against the transporter and a 10-nm gold conjugate of a secondary antibody. The distance between the luminal and abluminal membranes, represented by the red bar, is only 0.3 μm [55]. The GLUT1 transporter is also localized to the plasma membrane of red cells in the capillary lumen of the human brain. Reproduced, with permission, from [59]; copyright © 1994 Sage Publications. (D) Immunohistochemistry of rat brain with a primary antibody against the leptin receptor (LEPR) shows high enrichment of the receptors in the microvasculature of the brain, which appear as red cylinders within the brain tissue. Reproduced, with permission, from [60]; copyright © 1998 John Wiley & Sons. (E) Summary of literature findings on the immunohistochemistry of the brain using primary antibodies against specific receptors [55]. Expression of the insulin receptor (INSR), transferrin receptor 1 (TfR), the LEPR, and the insulin-like growth factor 1 receptor (IGF1R) is detected at both the brain capillary endothelium, which forms the BBB, and the brain cell plasma membrane. By contrast, immunochemistry of the brain shows that other receptors, which have been targeted for brain drug delivery, including the low-density lipoprotein receptor (LDLR), LDLR-related protein 1 (LRP1), the nicotinic acetylcholine receptor (nAChR), and the N-methyl D-aspartate receptor (NMDAR), are expressed on brain cells on the abluminal side of the BBB. Reproduced from [55], CC BY 4.0 license.