Background: Inflammation is a potential crucial factor in the pathogenesis of subarachnoid hemorrhage (SAH). Circulating microRNAs (miRNAs) are involved in the regulation of diverse aspects of neuronal dysfunction. The therapeutic potential of miRNAs has been demonstrated in several CNS disorders and is thought to involve modulation of neuroinflammation. Here, we found that peripherally injected modified exosomes (Exos) delivered miRNAs to the brains of mice with SAH and that the potential mechanism was regulated by regulation of neuroinflammation. Methods: Next-generation sequencing (NGS) and qRT-PCR were used to define the global miRNA profile of plasma exosomes in aSAH patients and healthy controls. We peripherally injected RVG/Exos/miR-193b-3p to achieve delivery of miR-193b-3p to the brain of mice with SAH. The effects of miR-193b-3p on SAH were assayed using a neurological score, brain water content, blood-brain barrier (BBB) injury, and Fluoro-Jade C (FJC) staining. Western blotting analysis, enzyme-linked immunosorbent assay (ELISA), and qRT-PCR were used to measure various proteins and mRNA levels. Results: NGS and qRT-PCR revealed that four circulating exosomal miRNAs were differentially expressed. RVG/Exos exhibited improved targeting to the brains of SAH mice. MiR-193b-3p suppressed the expression and activity of HDAC3, upregulating the acetylation of NF-κB p65. Finally, miR-193b-3p treatment mitigated the neurological behavioral impairment, brain edema, BBB injury, and neurodegeneration induced by SAH, and reduced inflammatory cytokine expression in the brains of mice after SAH. Conclusions: Exos/miR-193b-3p treatment attenuated the inflammatory response by acetylation of the NF-κB p65 via suppressed expression and activity of HDAC3. These effects alleviated neurobehavioral impairments and neuroinflammation following SAH.
Subarachnoid hemorrhage (SAH) is a complicated clinical syndrome, which is caused by several kinds of cerebrovascular disorders, with high morbidity, disability and mortality rate. In recent years, several studies have shown that early brain injury (EBI) is an important factor leading to the poor prognosis of SAH. A major cause of EBI has been attributed that hematoma components invade into the brain parenchyma, resulting in neuronal cell death. Therefore, the clearance of hematoma components is essential in the clinical outcome of patients after SAH. Here, in the review, we provide a summary of the current known hematoma components clearance mechanisms and simultaneously propose a new hypothesis for hematoma components clearance.
Nix is located in the outer membrane of mitochondria, mediates mitochondrial fission and implicated in many neurological diseases. However, the association between Nix and subarachnoid hemorrhage (SAH) has not previously been reported. Therefore, the present study was designed to evaluate the expression of Nix and its role in early brain injury (EBI) after SAH. Adult male Sprague-Dawley (SD) rats were randomly assigned to various time points for investigation after SAH. A rat model of SAH was induced by injecting 0.3 ml of autologous non-heparinized arterial blood into the prechiasmatic cistern. The expression of Nix was investigated by Western blot and immunohistochemistry. Next, Nix-specific overexpression plasmids and small interfering RNAs (siRNAs) were separately administered. Western blot, neurological scoring, Morris water maze, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining and fluoro-jade B (FJB) staining were performed to evaluate the role of Nix in EBI following SAH. We found that Nix was expressed in neurons and its expression level in the SAH groups was higher than that in the Sham group, which peaked at 24 h after SAH. Overexpression of Nix following SAH significantly decreased the expression of translocase of outer mitochondrial membrane 20 (TOMM20, a marker of mitochondria), ameliorated neurological/cognitive deficits induced by SAH, and reduced the total number of apoptotic/neurodegenerative cells, whereas siRNA knockdown of Nix yielded opposite effects. Taken together, our findings demonstrated that the expression of Nix is increased in neurons after experimental SAH in rats, and may play a neuroprotective role in EBI following SAH.
Objective To retrospective analyze the clinical data of 162 patients with small cerebellopontine angle meningiomas. To compare with the nature of tumors, symptoms pre- and post-treatments, neurological deficit, and prognosis in literatures. To explore the surgical outcomes of small cerebellopontine angle meningiomas and summarize the surgical experience. Methods All of 162 patients with small cerebellopontine angle meningiomas underwent surgery between January 2010 and December 2019 in the neurosurgery department of the First Affiliated Hospital of Soochow University. This cohort of eight literatures reported about stereotactic radiotherapy of small cerebellopontine angle meningiomas between January 2010 and December 2019. All clinical data were obtained for analysis. Results Compared with stereotactic radiotherapy, surgical treatment for small cerebellopontine angle meningiomas lead to the better results in relieving symptoms and inhibiting tumor progression. Surgical treatment can obtain the exact pathological examination results to guide the further treatment. Conclusions Surgical treatment should be the first choice for small cerebellopontine angle meningiomas.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.