TABLE 1.

Experimental and clinical approaches with BBB‐restoring efficacy in epilepsy and neurological disorders with a dysfunctional BBB.

Drug/therapeutic	Target/mode of action	Preclinical model	Clinical approach	Reference(s)
Propanolol	β‐adrenergic receptor antagonist, anti‐angiogenic, anti‐inflammatory		Repurposing in rare vascular diseases, e.g., CCM	[35]
RepSox	TGF‐β‐RI/ALK5 inhibitor, regulator of claudin‐5 expression	Kainic acid model of TLE		[160]
Ketogenic diet	GLUT1 targeting		Childhood epilepsy, recurrent glioblastoma	[10] [169]
Sunitinib, Anti‐VEGF antibodies / VEGFR2 pathway inhibitors	Tyrosine kinase inhibitor, VEGF inhibition, prevention of angiogenesis	Rat TLE model, Hippocampal cultures		[54] [8] [55]
Tie2 activators, Angiopoietin‐2 inhibitors	Angiopietin‐Tie2 signaling, vascular stabilization, edema prevention	Preclinical models for glioma, stroke, retinal diseases	Clinical trials for macula edema	[56] [57]
Everolimus, Rapamycin	mTOR antagonist	Rodent epilepsy models	Tuberous sclerosis complex	[10, 45] [46]
Dexamethasone	Glucocorticoid, stabilization of endothelial‐cell junctions, edema prevention	Rodent epilepsy models	Temporal lobe epilepsy, Glioblastoma	[10] [45, 46] [163]
Engineered Wnt ligands	Wnt/β‐catenin signaling	Preclinical glioma and stroke models		[62]
Losartan	Angiotensin‐type 1 receptor antagonist, TGFβ signaling inhibitor	Rodent epilepsy models		[80] [81] [82] [46]
Tariquidar	P‐gp inhibitor	Rodent epilepsy models		[70] [12]
IPR‐179	MMP2/9 inhibitor	Rodent epilepsy models		[87] [86]
Imatinib	Tyrosine kinase and PDGFR inhibitor	Hippocampal cultures	Chronic myeloid leukemia and glioblastoma‐associated epilepsy	[91] [46]
Natalizumab, Anti‐VCAM‐1 antibodies	α4 integrin, blockade of immune cell infiltration	Pilocarpine model of SE	Adjunctive therapy for patients with drug resistant epilepsy/Clinical phase II	[94] [95]
Verapamil	Calcium channel blocker, inhibitor of P‐gp		Adjuvant treatment in drug resistant epilepsy	[157, 158]

Abbreviations: BBB, blood–brain barrier; CCM, cerebral cavernous malformation; GLUT1, glucose transporter protein type 1; MMP, matrix metalloproteinase; mTOR, mammalian target of rapamycin; PDGFRβ, platelet‐derived growth factor receptor beta; P‐gp, P‐glycoprotein; SE, status epilepticus; TLE, temporal lobe epilepsy; TGF‐β‐RI/ALK5, transforming growth factor‐beta receptor I/activin like kinase 5; VCAM‐1, vascular cell adhesion molecule 1; VEGF, vascular endothelial growth factor.