Single Exposure to Low-Intensity Focused Ultrasound Causes Biphasic Opening of the Blood-Brain Barrier Through Secondary Mechanisms

Pharmaceutics, Journal Year: 2025, Volume and Issue: 17(1), P. 75 - 75

Published: Jan. 8, 2025

Background/Objective: The blood-brain barrier (BBB) is selectively permeable, but it also poses significant challenges for treating CNS diseases. Low-intensity focused ultrasound (LiFUS), paired with microbubbles a promising, non-invasive technique transiently opening the BBB, allowing enhanced drug delivery to central nervous system (CNS). However, downstream physiological effects following BBB opening, particularly secondary responses, are not well understood. This study aimed characterize time-dependent changes in permeability, transporter function, and inflammatory responses both sonicated non-sonicated brain tissues LiFUS treatment. Methods: We employed situ perfusion assess alterations integrity as multiplex cytokine analysis quantify response. Results: Our findings show that significantly increased vascular volume glucose uptake, reduced P-gp function six hours post treatment, indicating biphasic disruption. Additionally, elevated levels of pro-inflammatory cytokines, including TNF-α IL-6, were observed regions. A comparative between wild-type immunodeficient mice revealed distinct patterns release, showing lower serum concentrations IFN-γ TNF-α, highlighting potential impact immune status on response LiFUS. Conclusions: provides new insights into nature LiFUS-induced disruption, emphasizing importance understanding timing extent changes.

Language: Английский

La maladie de Parkinson : de la génétique aux thérapies ciblées

Comptes Rendus Biologies, Journal Year: 2025, Volume and Issue: 348(G1), P. 21 - 33

Published: Feb. 13, 2025

La maladie de Parkinson (MP) est une multifactorielle impliquant des facteurs génétiques et environnementaux. Cependant, l'âge début, l'étendue lésions la rapidité progression peuvent varier façon considérable, ce qui conduit à s'interroger sur l'unicité MP. L'identification formes monogéniques, dont certaines semblent impliquer mécanismes différents, renforce l'hypothèse distinctes partagent présence d'un syndrome parkinsonien. Alors que le gène SNCA fût premier identifié dans les rares, variants pathogènes gènes GBA1 LRRK2 représentent causes ou risque MP plus communs, PRKN souvent impliqué autosomiques récessives Les patients présentant SNCA, GBA1, diffèrent par leurs caractéristiques cliniques, anatomopathologiques biochimiques. Ainsi, ces quatre associés sont intérêt tout particulier pour développement thérapeutiques spécifiques, d'autant approches actuelles restent symptomatiques. essais cliniques fondés nature du débutent. Dans cette revue, nous présentons principales physiopathologiques avant discuter nouvelles ciblent spécifiquement. Parkinson's disease (PD) is a multifactorial disorder involving various biological pathways. However, it more accurate not to define PD as unique entity, but rather mixture of several diseases with similar phenotypes. Attempts classify subtypes based on the clinical phenotype or biomarkers were tried. Nonetheless, for subset individuals, classification implied gene appears be most practical. Although was first identified in rare patients, pathogenic and are common genetic risk factors PD, frequent autosomal recessive PD. Patients show clinical, anatomopathological biochemical aspects. Therefore, these four genes associated particular interest development targeted therapies. This fact reinforced by reality that current approaches only symptomatic, no curative treatment available today. A number trials aiming slow stop running, involved. In this review, we will discuss therapeutic targeting PRKN.

Wnt-Regulated Therapeutics for Blood-Brain Barrier Modulation and Cancer Therapy

Bioconjugate Chemistry, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 16, 2024

The Wnt signaling pathway has a significant regulatory part in tissue development and homeostasis. Dysregulation of the been associated with many diseases including cancers various brain diseases, making this promising therapeutic target for these diseases. In review, we describe roles blood-brain barrier (BBB) intracranial tumors peripheral tumors, from preclinical clinical perspectives, introduce Wnt-regulated therapeutics types drugs nanomedicines as BBB modulators brain-oriented drug delivery cancer treatments, finally discuss limitations future perspectives therapeutics.

Language: Английский