Table 2.

Diseases linked to BBB dysfunction

Disease	Level of BBB effect*	Comment	Refs
Stroke	Primary	Microvascular injury induced by oxidative stress during ischemia/reperfusion	160
Epilepsy	Primary	Systemic inflammation can disturb brain homeostasis by allowing entry of ions and epileptogenic substances across the BBB	161,162
	Secondary	Seizures reduce BBB integrity, which enables entry of plasma proteins into the brain that sustain the epileptogenic state
AD	Primary	BBB dysfunction, including defective amyloid-beta clearance from brain and congophilic angiopathy	163,164
Familial ALS	Primary	Loss of BBB integrity at an ultrastructural level, associated with expression of mutant SOD1 in brain capillary endothelial cells	164,165
PD	Secondary	Increased BBB permeability and decreased transport activity across the BBB, including inefficient efflux of toxic molecules via P-glycoprotein	166,167
MS	Secondary	Extravasation of autoreactive T cells and monocytes across a compromised BBB	168
Natalizum ab-PML with IRIS	Secondary	Infiltration of T cells in perivascular space and parenchyma after discontinuation of Natalizumab in context of PML	169
NMO	Primary	BBB breakdown including loss of AQP4 and of astrocytes caused by AQP4-IgG	170
Primary CNS vasculitis	Primary	Inflammation of cerebral vessels without systemic disorder	171,172
Secondary CNS vasculitis	Primary	Inflammation of cerebral vessels associated with systemic inflammatory illness	171
VZV vasculopathy	Primary	Viral infection (primary or upon reactivation) of cerebral arteries	173
Cerebral malaria	Primary	Sequestration of parasitized red blood cells in lumen of cerebral microvasculature	174
Primary CNS lymphoma	Secondary	Leaky angiogenic vessels in malignant tissue	175
Glioblastoma	Secondary	Leaky neo-angiogenic vessels and loss of BBB integrity in pre-existing vessels (by subcellular mislocalization of astroglial AQP4) in malignant tissue	176
PRES	Primary	Vascular injury by systemic influence, such as disorders of clotting or bleeding, and chemotherapy agents (particularly those which inhibit VEGFR kinase)	177
TBI	Secondary	Mechanical disruption of BBB followed by post-traumatic BBB dysfunction	178
Migraine	Secondary	Cortical spreading depression with subsequent vascular reaction	179
Diabetes	Secondary	Increased BBB permeability, possibly leading to cognitive impairment	180

^*Primary level of BBB effect indicates that the cerebrovasculature is probably compromised upstream from CNS pathogenesis whereas secondary level of BBB effect is interpreted as happening downstream from the initial insult and aggravating disease.

AD, Alzheimer’s disease; ALS, Amyotrophic lateral sclerosis; PD, Parkinson’s disease; MS, Multiple sclerosis; PML, Progressive multifocal leukoencephalopathy; IRIS, Immune reconstitution inflammatory syndrome; NMO, Neuromyelitis optica; VZV, Varizella zoster virus; PRES, Posterior reversible encephalophathy syndrome; TBI, Traumatic brain injury