Microbubbles (MB) are widely used for ultrasound (US) imaging and drug delivery. MB are typically spherically shaped, due to surface tension. When heated above their glass transition temperature, polymer-based MB can be mechanically stretched to obtain an anisotropic shape, endowing them with unique features for US-mediated blood-brain barrier (BBB) permeation. It is here shown that nonspherical MB can be surface-modified with BBB-specific targeting ligands, thereby promoting binding to and sonopermeation of blood vessels in the brain. Actively targeted rod-shaped MB are generated via 1D stretching of spherical poly(butyl cyanoacrylate) MB and via subsequently functionalizing their shell with antitransferrin receptor (TfR) antibodies. Using US and optical imaging, it is demonstrated that nonspherical anti-TfR-MB bind more efficiently to BBB endothelium than spherical anti-TfR-MB, both in vitro and in vivo. BBB-associated anisotropic MB produce stronger cavitation signals and markedly enhance BBB permeation and delivery of a model drug as compared to spherical BBB-targeted MB. These findings exemplify the potential of antibody-modified nonspherical MB for targeted and triggered drug delivery to the brain.
Gliomas are the most common tumors of the central nervous system, with glioblastoma (GBM) being particularly aggressive and fatal. Current treatments for GBM, including surgery and chemotherapy, are limited by tumor aggressiveness and the blood-brain barrier. Therefore, understanding the molecular mechanisms driving GBM growth is essential.
Background: Chronic arterial hypertension restructures the vascular architecture of the brain, leading to a series of pathological responses that culminate in cerebral small-vessel disease. Pericytes respond dynamically to vascular challenges; however, how they manifest under the continuous strain of hypertension has not been elucidated.
Methods And Results: In this study, we characterized pericyte behavior alongside hypertensive states in the spontaneously hypertensive stroke-prone rat model, focusing on their phenotypic and metabolic transformation.
Hospital & Institute of Obstetrics and Gynecology, Fudan University, Shanghai 200081, China; The Academy of Integrative Medicine, Fudan University, Shanghai 200081, China; Shanghai Key Laboratory of Female Reproductive Endocrine-related Disease, Shanghai 200081, China. Electronic address:
Polycystic ovary syndrome (PCOS) has been noticed as a neuroendocrine syndrome manifested by reproductive hormone dysregulation involving increased luteinizing hormone (LH) pulse frequency and an increased LH to follicle-stimulating hormone ratio, yet theory is just beginning to be established. Neuroglia located in the arcuate nucleus and median eminence (ARC-ME) that are close to gonadotropin-releasing hormone (GnRH) axon terminals, comprise the blood-brain barrier and fenestrated vessels implying their putative roles in the modulation of the abnormal GnRH pulse in PCOS. This review outlines the disturbances of neuron-glia networks that underlie hypothetically the deregulation of GnRH-LH release and impaired sex hormone negative feedback in PCOS.
This study presents the first in vivo measurement of transcytolemmal water exchange in the brain using a novel Magnetic Resonance technique. We extend previous applications of Chemical Exchange Saturation Transfer (CEST) to examine water exchange across cellular membranes in late-stage chicken embryo brains. The immature blood-brain barrier at this stage allows Gadolinium-Based Contrast Agents (GBCAs) to penetrate the brain's interstitial space, sensitizing the CEST effect to water exchange between intra- and extracellular environments.
Unlabelled: Hepatic encephalopathy is an early and severe complication of obstructive jaundice and is characterized by occurrence of non-focal and focal neurological manifestations. Different methods of therapy are applied for disorder correction. Low-intensity laser blood irradiation has a pronounced antioxidant and vasoactive effect.
