Our findings suggest that the inflammation-prone HD astrocytes provide less pericyte coverage by promoting angiogenesis and reducing the number of pericytes and that these changes can explain the inferior VR in HD mice. The resultant impaired VR might hinder cerebral hemodynamics and increase brain atrophy during HD progression.
The
repair of the central nervous system (CNS) is a major challenge
because of the difficulty for neurons or axons to regenerate after
damages. Injectable hydrogels have been developed to deliver drugs
or cells for neural repair, but these hydrogels usually require conditional
stimuli or additional catalysts to control the gelling process. Self-healing
hydrogels, which can be injected locally to fill tissue defects after
stable gelation, are attractive candidates for CNS treatment. In the
current study, the self-healing hydrogel with a semi-interpenetrating
polymer network (SIPN) was prepared by incorporation of hyaluronan
(HA) into the chitosan-based self-healing hydrogel. The addition of
HA allowed the hydrogel to pass through a narrow needle much more
easily. As the HA content increased, the hydrogel showed a more packed
nanostructure and a more porous microstructure verified by coherent
small-angle X-ray scattering and scanning electron microscopy. The
unique structure of SIPN hydrogel enhanced the spreading, migration,
proliferation, and differentiation of encapsulated neural stem cells
in vitro. Compared to the pristine chitosan-based self-healing hydrogel,
the SIPN hydrogel showed better biocompatibility, CNS injury repair,
and functional recovery evaluated by the traumatic brain injury zebrafish
model and intracerebral hemorrhage rat model. We proposed that the
SIPN of HA and chitosan self-healing hydrogel allowed an adaptable
environment for cell spreading and migration and had the potential
as an injectable defect support for CNS repair.
Despite extensive efforts in recent years, the blood-brain barrier (BBB) remains a significant obstacle for drug delivery. This study proposes using a clinical extracorporeal shockwave instrument to open the BBB, combined with a laser assisted bi-axial locating platform to achieve non-invasive, controllable-focus and reversible BBB opening in the brains of rats. Under shockwave treatment with an intensity level of 5 (P–9.79 MPa, energy flux density (EFD) 0.21 mJ/mm2) and a pulse repetition frequency of 5 Hz, the BBB could be opened after 50 shocks without the use of an ultrasound contrast agent. With the proposed method, the BBB opening can be precisely controlled in terms of depth, size and location. Moreover, a shockwave based gene transfection was demonstrated using a luciferase gene.
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