iPSC-derived exosomes as amphotericin B carriers: a promising approach to combat cryptococcal meningitis DOI Creative Commons
Jingyu Zhao,

Wei Fang,

Yangjie Gao

et al.

Frontiers in Microbiology, Journal Year: 2025, Volume and Issue: 16

Published: Feb. 10, 2025

Background Cryptococcal meningitis (CM) is a significant global health issue, particularly affecting individuals with HIV. Amphotericin B (AmB) serves as the cornerstone treatment for CM; however, its clinical application restricted due to limited penetration of blood–brain barrier and associated nephrotoxicity. Objective This study investigates use exosomes derived from induced pluripotent stem cells (iPSC-Exos) carriers AmB in treating CM, aiming enhance therapeutic efficacy safety reduce toxicity. Methods Exosomes were extracted iPSC culture supernatants using ultrafiltration ultracentrifugation. Their morphology size analyzed transmission electron microscopy (TEM) nanoparticle flow cytometry (nFCM). Purity was confirmed by Western blotting markers CD9, CD63, TSG101. loaded into iPSC-Exos co-incubation method. The cytotoxicity iPSC-Exo/AmB complex evaluated on HEK 293 T RAW264.7 CCK-8 assay, while apoptosis assessed live/dead cell staining cytometry. hemolytic effects tested rabbit red blood cells. In C57BL/6 J mouse model cryptococcal infection, groups (AmB, iPSC-Exo/AmB, iPSC-Exo) administered corresponding drugs, brain samples collected analysis. minimum inhibitory concentration (MIC) conventional against Cryptococcus determined. Results exhibited reduced vitro decreased AmB-induced renal hepatic toxicity vivo . Its MIC over eight times lower than AmB, significantly reducing fungal burden lowering serum inflammatory factors. Conclusion promising strategy that enhances toxicity, offering new hope CM other refractory infections central nervous system.

Language: Английский

The blood-brain barrier in aging and neurodegeneration DOI Creative Commons
Emily G. Knox, María R. Aburto, Gerard Clarke

et al.

Molecular Psychiatry, Journal Year: 2022, Volume and Issue: 27(6), P. 2659 - 2673

Published: March 31, 2022

Abstract The blood-brain barrier (BBB) is vital for maintaining brain homeostasis by enabling an exquisite control of exchange compounds between the blood and parenchyma. Moreover, BBB prevents unwanted toxins pathogens from entering brain. This barrier, however, breaks down with age further disruption a hallmark many age-related disorders. Several drugs have been explored, thus far, to protect or restore function. With recent connection gut microbiota, microbial-derived metabolites explored their capabilities physiology. review, will focus on components that make up BBB, dissect levels discuss current therapeutics maintain integrity discoveries effects

Language: Английский

Citations

386
Brain drug delivery and neurodegenerative diseases: Polymeric PLGA-based nanoparticles as a forefront platform DOI
Miguel Pinto, Vera Silva, Sandra Barreiro

et al.

Ageing Research Reviews, Journal Year: 2022, Volume and Issue: 79, P. 101658 - 101658

Published: June 2, 2022

Language: Английский

Citations

55
Environmental exposure of the general population to cadmium as a risk factor of the damage to the nervous system: A critical review of current data DOI Creative Commons
Agnieszka Ruczaj, Małgorzata M. Brzóska

Journal of Applied Toxicology, Journal Year: 2022, Volume and Issue: 43(1), P. 66 - 88

Published: March 19, 2022

Abstract Nowadays, more and attention has been focused on the risk of neurotoxic action cadmium (Cd) under environmental exposure. Due to growing incidence nervous system diseases, including neurodegenerative changes, suggested involvement Cd in their aetiopathogenesis, this review aimed discuss critically element neurotoxicity. Attempts have made recognize at which concentrations blood urine may increase damage compare it injury other organs systems. The performed overview available literature shows that an unfavourable impact human's concentration >0.8 μg Cd/L >0.6 blood. Because such are currently noted general population industrialized countries, can be concluded exposure xenobiotic create a involved aetiopathogenesis as Alzheimer's disease Parkinson's disease, well worsening cognitive behavioural functions. potential mechanism neurotoxicity consists inducing oxidative stress, disrupting activity enzymes essential proper functioning destroying homoeostasis bioelements brain. Thus, further studies necessary accurately both due action.

Language: Английский

Citations

54
Blood–Brain Barrier Disruption and Its Involvement in Neurodevelopmental and Neurodegenerative Disorders DOI Open Access
Ana Aragón-González, Pamela J. Shaw, Laura Ferraiuolo

et al.

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(23), P. 15271 - 15271

Published: Dec. 3, 2022

The blood–brain barrier (BBB) is a highly specialized and dynamic compartment which regulates the uptake of molecules solutes from blood. relevance maintenance healthy BBB underpinning disease prevention as well main pathomechanisms affecting function will be detailed in this review. Barrier disruption common aspect both neurodegenerative diseases, such amyotrophic lateral sclerosis, neurodevelopmental including autism spectrum disorders. Throughout review, conditions altering during earliest latest stages life discussed, revealing factors involved. Due to barrier’s role protecting brain exogenous components xenobiotics, drug delivery across challenging. Potential therapies based on properties molecular Trojan horses, among others, reviewed, innovative treatments stem cell therapies. Additionally, due microbiome influence normal brain, microflora modulation strategies discussed. Finally, future research directions are highlighted address current gaps literature, emphasizing idea that for pathologies exist.

Language: Английский

Citations

44
Addressing Blood–Brain Barrier Impairment in Alzheimer’s Disease DOI Creative Commons
Chanchal Sharma,

Hanwoong Woo,

Sang Ryong Kim

et al.

Biomedicines, Journal Year: 2022, Volume and Issue: 10(4), P. 742 - 742

Published: March 22, 2022

The blood–brain barrier (BBB) plays a vital role in maintaining the specialized microenvironment of brain tissue. It facilitates communication while separating peripheral circulation system from parenchyma. However, normal aging and neurodegenerative diseases can alter damage physiological properties BBB. In this review, we first briefly present essential pathways regulating BBB integrity, further review mechanisms breakdown associated with inflammation-causing neurodegeneration cognitive impairments. We also discuss how disruption cause or contribute to Alzheimer’s disease (AD), most common form dementia devastating neurological disorder. Next, document overlaps between AD vascular (VaD) sum up techniques for identifying biomarkers linked deterioration. Finally, conclude that could be used as biomarker help diagnose impairment such AD.

Language: Английский

Citations

41
Unveiling the impact of aging on BBB and Alzheimer's disease: Factors and therapeutic implications DOI
Niraj Kumar Jha, Niraj Kumar Jha, Mohana Vamsi Nuli

et al.

Ageing Research Reviews, Journal Year: 2024, Volume and Issue: 98, P. 102224 - 102224

Published: Feb. 10, 2024

Language: Английский

Citations

14
Dysregulation of Ion Channels and Transporters and Blood-Brain Barrier Dysfunction in Alzheimer’s Disease and Vascular Dementia DOI Creative Commons
Ruijia Liu,

Jenelle M Collier,

Nana-Hawwa Abdul-Rahman

et al.

Aging and Disease, Journal Year: 2024, Volume and Issue: unknown

Published: Jan. 1, 2024

The blood-brain barrier (BBB) plays a critical role in maintaining ion and fluid homeostasis, essential for brain metabolism neuronal function. Regulation of nutrient, water, transport across the BBB is tightly controlled by specialized transporters channels located within its unique cellular components. These dynamic processes not only influence BBB’s structure but also impact vital signaling mechanisms, optimal Disruption ion, pH, balance at associated with pathology has been implicated various neurological conditions, including stroke, epilepsy, trauma, neurodegenerative diseases such as Alzheimer’s disease (AD). However, knowledge gaps exist regarding dysregulation on function dementias. Several factors contribute to this gap: complex nature these historical research focus mechanisms technical challenges studying in vivo models lack efficient vitro dementia models. This review provides an overview current roles poses specific questions: 1) How are expression activity key altered AD vascular (VaD); 2) Do changes dysfunction progression; 3) Can restoring mitigate improve clinical outcomes. Addressing will provide greater insight into disorders.

Language: Английский

Citations

9
Breaking Barriers in Huntington’s Disease Therapy: Focused Ultrasound for Targeted Drug Delivery DOI Creative Commons

M.D. HEBAT-ALLAH G. RASHED SHAABAN R. HELAL,

Amna Ibrahim,

Ahmad Beddor

et al.

Neurochemical Research, Journal Year: 2025, Volume and Issue: 50(1)

Published: Jan. 3, 2025

Abstract Huntington’s disease (HD) is a progressive neurodegenerative resulting from mutation in the huntingtin (HTT) gene and characterized by motor dysfunction, cognitive decline, psychiatric disturbances. Currently, no disease-modifying treatments are available. Recent research has developed therapeutic agents that may have potential to directly target pathology, such as silencing or clearing mutant protein. However, these limited their inability cross blood-brain barrier (BBB), preventing optimal effects. Although various techniques been explored overcome BBB, focused ultrasound (FUS) emerged promising non-invasive modality offering for targeted intervention diseases, including HD. Preclinical studies demonstrated safety efficacy of FUS delivering agents, siRNAs AAV vector-based therapy, significant reductions HTT expression improvements function HD mouse models. Furthermore, profile FUS-induced BBB opening established clinical trials on human patients diseases other than HD, showing adverse effects brain structure function. This review provides comprehensive overview current state connects existing evidence with its promise establishing therapies Graphical

Language: Английский

Citations

1
Nanotechnology to Overcome Blood–Brain Barrier Permeability and Damage in Neurodegenerative Diseases DOI Creative Commons
Adriana Jiménez, Enrique Estudillo, Mara A. Guzmán‐Ruiz

et al.

Pharmaceutics, Journal Year: 2025, Volume and Issue: 17(3), P. 281 - 281

Published: Feb. 20, 2025

The blood–brain barrier (BBB) is a critical structure that maintains brain homeostasis by selectively regulating nutrient influx and waste efflux. Not surprisingly, it often compromised in neurodegenerative diseases. In addition to its involvement these pathologies, the BBB also represents significant challenge for drug delivery into central nervous system. Nanoparticles (NPs) have been widely explored as carriers capable of overcoming this effectively transporting therapies brain. However, their potential directly address ameliorate dysfunction has received limited attention. review, we examine how NPs enhance across treat diseases explore emerging strategies restore integrity vital structure.

Language: Английский

Citations

1
Blood brain barrier-on-a-chip to model neurological diseases DOI

S. Reshma,

K. B. Megha,

S. Amir

et al.

Journal of Drug Delivery Science and Technology, Journal Year: 2023, Volume and Issue: 80, P. 104174 - 104174

Published: Jan. 18, 2023

Language: Английский

Citations

17