A variety of neuroprotectants have shown promise in treating ischemic stroke, yet their delivery to the brain remains a challenge. The endothelial cells lining the blood-brain barrier (BBB) are emerging as a dynamic factor in the response to neurological injury and disease, and the endothelial-neuronal matrix coupling is fundamentally neuroprotective. In this review, we discuss approaches that target the endothelium for drug delivery both across the BBB and to the BBB as a viable strategy to facilitate neuroprotective effects, using the example of brain-derived neurotrophic factor (BDNF). We highlight the advances in cell-derived extracellular vesicles (EVs) used for CNS targeting and drug delivery. We also discuss the potential of engineered EVs as a potent strategy to deliver BDNF or other drug candidates to the ischemic brain, particularly when coupled with internal components like mitochondria that may increase cellular energetics in injured endothelial cells.
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http://dx.doi.org/10.1016/j.addr.2021.01.015 | DOI Listing |
Metab Brain Dis
January 2025
The Second Affiliated Hospital of Guilin Medical University, Guilin Medical University, Guilin, 541199, Guangxi, China.
Type 2 diabetes (T2D) is an important risk factor for brain cognitive impairment, but the specific mechanism is still unclear. The imbalance of gut microbiota under pathological conditions (such as an increase in pathogenic bacteria) may be involved in the occurrence of various diseases. The purpose of this study is to investigate the effect of increased abundance of gut Citrobacter rodentium on cognitive function in T2D mice.
View Article and Find Full Text PDFMetab Brain Dis
January 2025
Department of Biochemistry, Faculty of Science, University of Yaoundé 1, P.O. Box 812, Yaounde, Cameroon.
Alzheimer's disease (AD) is associated with cognitive impairments which are linked to a deficit in cholinergic function. The objective of this study was to evaluate the ability of TeMac™ to prevent memory impairment in scopolamine-rats model of Alzheimer's disease and by in silico approaches to identify molecules in TeMac™ inhibiting acetylcholinesterase. The cholinergic cognitive dysfunction was induced by intraperitoneal injection of scopolamine (1 mg/kg daily) in male Wistar rats for seven consecutive days.
View Article and Find Full Text PDFAlzheimers Dement
January 2025
Institute for Biomedical Engineering and Institute of Pharmacology and Toxicology, Faculty of Medicine, University of Zurich, Zurich, Switzerland.
Introduction: Transcranial pulse stimulation (TPS) is increasingly being investigated as a promising potential treatment for Alzheimer's disease (AD). Although the safety and preliminary clinical efficacy of TPS short pulses have been supported by neuropsychological scores in treated AD patients, its fundamental mechanisms are uncharted.
Methods: Herein, we used a multi-modal preclinical imaging platform combining real-time volumetric optoacoustic tomography, contrast-enhanced magnetic resonance imaging, and ex vivo immunofluorescence to comprehensively analyze structural and hemodynamic effects induced by TPS.
J Cell Physiol
January 2025
Department of Pharmaceutical Sciences and Center for Blood-Brain Barrier Research, Jerry H. Hodge School of Pharmacy, Texas Tech University Health Sciences Center, Amarillo, Texas, USA.
Glucose is a major source of energy for the brain. At the blood-brain barrier (BBB), glucose uptake is facilitated by glucose transporter 1 (GLUT1). GLUT1 Deficiency Syndrome (GLUT1DS), a haploinsufficiency affecting SLC2A1, reduces glucose brain uptake.
View Article and Find Full Text PDFActa Pharm Sin B
December 2024
Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, West China School of Pharmacy, Mental Health Center and National Chengdu Center for Safety Evaluation of Drugs, West China Hospital, Sichuan University, Chengdu 610041, China.
The neurovascular unit (NVU) is highly responsible for cerebral homeostasis and its dysfunction emerges as a critical contributor to Alzheimer's disease (AD) pathology. Hence, rescuing NVU dysfunction might be a viable approach to AD treatments. Here, we fabricated a self-regulated muti-functional nano-modulator (siR/PIO@RP) that can intelligently navigate to damaged blood-brain barrier and release therapeutical cargoes for synergetic AD therapy.
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