blood–brain barrier

Overview

The blood–brain barrier (BBB) is a specialized biological interface formed primarily by brain microvascular endothelial cells and their associated supporting cells, including astrocytes and pericytes. It tightly regulates the exchange of molecules, ions, and cells between the bloodstream and the central nervous system (CNS), thereby maintaining neural homeostasis and protecting the brain from toxins, pathogens, and inflammatory mediators. Functionally, the BBB is not a passive wall but a dynamic, selectively permeable barrier whose properties can change in development, adulthood, aging, and disease.

From a biomedical perspective, the BBB is central to both neuroprotection and therapeutic delivery. Its restrictive transport properties limit entry of many drugs, including agents intended for Alzheimer’s disease, glioblastoma, epilepsy, fungal encephalitis, and other CNS disorders. At the same time, BBB disruption is a hallmark of several pathological states, including ischemic stroke, meningitis, neuroinflammation, and brain metastasis, where barrier breakdown can worsen injury or alter disease progression. Transport systems such as LAT1 and P-glycoprotein (P-gp) are frequently studied because they influence BBB penetration and oral bioavailability of candidate therapeutics.

Focus of Latest Publications

Recent publications have focused on the blood-brain barrier as a therapeutic and prognostic target across acute and chronic neurological disease, as well as in drug delivery and tissue repair. In acute ischemic stroke with large vessel occlusion, one study examined whether blood-brain barrier disruption assessed before interhospital transfer for thrombectomy is associated with 24-hour hemorrhagic transformation and 3-month functional outcome. In a related stroke model, NADPH was reported to preserve blood-brain barrier integrity after transient middle cerebral artery occlusion, reducing infarct volume, cerebral edema, and neurological deficits while also lowering matrix metalloproteinase-9 and caveolin-1, suppressing NLRP3 inflammasome activation, and increasing tight junction protein ZO-1.

Several studies addressed blood-brain barrier disruption in neurodegenerative disease and its relationship to systemic or metabolic factors. In Alzheimer's disease patients with high body mass index, investigators reported worse cognition alongside elevated cerebrospinal fluid levels of ZO-1 and occludin, interpreted as blood-brain barrier disruption, together with increased markers of neuroinflammation such as nitric oxide and hydroxyl radical. The study also linked BMI, gut dysbiosis-related metabolites, blood-brain barrier variables, and neuroinflammatory factors, suggesting a gut-brain axis contribution to cognitive decline. Separately, DeepDrugDiscovery incorporated blood-brain barrier penetrability prediction into an AI screening pipeline and identified novel mTOR-independent autophagy enhancers; two lead compounds were reported to cross the blood-brain barrier, clear Alzheimer's disease-related protein aggregates, and restore memory in worm and mouse models.

Other publications explored blood-brain barrier transport and repair in therapeutic development. In glioblastoma multiforme, biotin-decorated inulin-based polymeric micelles loaded with curcumin were evaluated for dual targeting of the blood-brain barrier and tumor cells; the micelles showed favorable physicochemical properties, enhanced cellular uptake and retention, and improved crossing of the blood-brain barrier with increased drug accumulation in biotin receptor-overexpressing glioblastoma cells. In triple-negative breast cancer, the peptide p28 was described as having favorable blood-brain barrier permeability while enhancing chemotherapy, inducing apoptosis, reducing invasion and metastasis, and lowering toxicity in preclinical models. In traumatic brain injury, a dried platelet-derived biologic reduced intracranial hemorrhage, attenuated blood-brain barrier permeability, and mitigated neuroinflammation, with mechanistic data implicating angiopoietin-1 and Tie2 signaling in vascular protection.

Key Publications

• NEWJul Blood-Brain Barrier Disruption Before Interhospital Transfer for Thrombectomy and Clinical Outcome. (Neurology, 2026, PMID 42385121): "We aimed to determine whether blood-brain barrier (BBB) disruption assessed before interhospital transfer for EVT is associated with 24-hour hemorrhagic transformation (HT) and 3-month functional outcome."
• Jun Gut-brain axis crosstalk in patients with Alzheimer's disease and high body mass index: Gut dysbiosis, blood-brain barrier disruption, and neuroinflammation. (Journal of Alzheimer's disease : JAD, 2026, PMID 42227185): "...potential mechanisms involving gut dysbiosis, blood-brain barrier (BBB) disruption, and neuroinflammation in brain."
• May A multi-targeted therapeutic strategy for triple-negative breast cancer: the tumor-targeting peptide p28 enhances chemotherapy, induces apoptosis, crosses the blood-brain barrier, and suppresses metastasis. (Apoptosis : an international journal on programmed cell death, 2026, PMID 42095973): "The tumor-targeting peptide p28, which exhibits antitumor activity and potential blood-brain barrier (BBB) penetration, represents a promising candidate for enhancing therapeutic efficacy in TNBC through distinct mechanisms of action."
• Apr DeepDrugDiscovery identifies blood-brain barrier permeable autophagy enhancers for Alzheimer's disease. (Nature biomedical engineering, 2026, PMID 42032039): "with two lead compounds demonstrating an ability to cross the blood-brain barrier, clear AD-related protein aggregates and restore memory function in worm and mouse AD models."
• May Biotin-Decorated Inulin-Based Polymeric Micelles Unveil Their Dual-Targeting Ability for the Potential Treatment of Glioblastoma Multiforme through the In Vitro and In Vivo Investigations. (Molecular pharmaceutics, 2026, PMID 41973041): "This study evaluated biotinylated-inulin vitamin E micelles (INVITE-BIO) as a carrier for the hydrophobic drug curcumin and their biotin-mediated dual-targeting ability to the Blood-Brain Barrier (BBB) and Glioblastoma Multiforme (GBM) cells by in vitro and in vivo studies."
• Jun A dried platelet-derived biologic for blood-brain barrier repair and hemorrhage control after TBI in mice. (Blood, 2026, PMID 41843452): "The blood-brain barrier (BBB) and regulation of vascular stability after injury are emerging as critical therapeutic targets."
• May NADPH exerts neuroprotection in ischemic stroke by reinforcing blood-brain barrier integrity and stimulating angiogenesis. (Neuropharmacology, 2026, PMID 41638470): "This study explored the neuroprotective effects of nicotinamide adenine dinucleotide phosphate (NADPH) in preserving blood-brain barrier (BBB) integrity and promoting angiogenesis after IS."