Table 1 Common molecular pathways involved in BBB dysfunction in TBI and AD

ApoE4

Expression impairs BBB repair [71]

Expression leads to BBB breakdown [70]

ApoE antisense oligonucleotides [81], siRNAs [82] or antibodies [83] reduce Aβ and tau pathology and rescue cerebrovascular dysfunction [83]

TGF-β

Increased [86]

Impaired [86]

Treatment with an inhibitor prevents BBB leakage and reduces neurological deficits [34]

Mfsd2a

Reduced [96,97,98]

Decreased [99]

Overexpression improves BBB function, and abolishes neurologic impairment [96]

Overexpression reverses learning and memory impairments [102]

Wnt

Increased [117]

Impaired [110]

Activation restores BBB function and ameliorates AD pathology [119]

Activation mitigates BBB disruption and improves outcomes [98]

MMP-9

Increased [126]

Upregulated [72, 127]

Ablation decreases BBB permeability, and improves memory [126]

Deletion improves memory [128]

Treatment with an inhibitor improves memory [128]

Shh

Impaired [131]

Blocking reduces neuronal apoptosis and improves learning and memory [136]

Shh treatment attenuates BBB dysfunction and promotes neurological recovery [131]

mTOR

Activated [148]

Activation worsens neurocognitive outcome [149]

Inhibition ameliorates symptoms and inflammation [150]

Inhibition abrogates BBB breakdown [144], and reverses memory deficits (145)