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Table 1 Different CNS pathological conditions involving BBB disruption

From: A blood–brain barrier overview on structure, function, impairment, and biomarkers of integrity

CNS pathology BBB dysfunction
Stroke Astrocytes secrete transforming growth factor-β (TGFβ), which downregulates brain capillary endothelial
Expression of fibrinolytic enzyme tissue
Plasminogen activator (tPA) and anticoagulant thrombomodulin (TM)
Proteolysis of vascular basement membrane/matrix
Induction of aquaporin 4 (AQP4) mRNA and protein at BBB disruption
Trauma Bradykinin (an inflammatory mediator) stimulates the production and the release of interleukin-6 (IL-6) from astrocytes, leading to the opening of the BBB
Infectious or inflammatory processes e.g., bacterial infections, meningitis, encephalitis, and sepsis
The bacterial protein lipopolysaccharide (LPS) affects the permeability of BBB tight junctions. This is mediated by the production of free radicals, IL-6, and IL-1 β
Interferon-β prevents BBB disruption
Alterations in P-glycoprotein expression and activity in the BBB
Increased pinocytosis in brain microvessel endothelium and swelling of astrocytes end-feet
Multiple sclerosis Breakdown of the BBB
Tight junction abnormalities
Downregulation of laminin in the basement membrane
Selective loss of claudin3 in experimental autoimmune encephalomyelitis
HIV BBB tight junction disruption
Cytokines secretion by activated macrophages and astrocytes, e.g., TNF-α, NO, platelet-activating factor, and quinolinic acid
Alzheimer’s disease Decreased glucose transport, downregulation of glucose transporter GLUT1, altered agrin levels, upregulation of AQP4 expression
Accumulation of amyloid-β, a key neuropathological feature of Alzheimer’s disease, by decreased levels of P-glycoprotein transporter expression
Altered cellular relations at the BBB, and changes in the basal lamina and amyloid-β clearance
Parkinson’s disease Dysfunction of the BBB by reduced efficacy of P-glycoprotein
Epilepsy Transient BBB opening in epileptogenic foci, and upregulated expression of P-glycoprotein and other drug efflux transporters in astrocytes and endothelium
Brain tumors Breakdown of the BBB
Downregulation of tight junction protein claudin 1, 3, and occludin; redistribution of astrocyte AQP4 and Kir4.1 (inwardly rectifying K+ channel)
Pain Inflammatory pain alters BBB tight junction protein expression and BBB permeability
Glaucoma Opening of the BBB, possibly through the diffusion of endothelin-1 and matrix-metalloproteinase-9 into peri-capillary tissue
Lysosomal storage diseases (LSD) May show changes in BBB permeability, and/or transport, depending on specific LSD
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