Table 1 Different CNS pathological conditions involving BBB disruption

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