neurovascular remodeling
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Biomolecules ◽  
2022 ◽  
Vol 12 (1) ◽  
pp. 115
Author(s):  
Lingling Jiang ◽  
Weiqi Chen ◽  
Jinyi Ye ◽  
Yilong Wang

Ischemic stroke is a life-threatening cerebral vascular disease and accounts for high disability and mortality worldwide. Currently, no efficient therapeutic strategies are available for promoting neurological recovery in clinical practice, except rehabilitation. The majority of neuroprotective drugs showed positive impact in pre-clinical studies but failed in clinical trials. Therefore, there is an urgent demand for new promising therapeutic approaches for ischemic stroke treatment. Emerging evidence suggests that exosomes mediate communication between cells in both physiological and pathological conditions. Exosomes have received extensive attention for therapy following a stroke, because of their unique characteristics, such as the ability to cross the blood brain–barrier, low immunogenicity, and low toxicity. An increasing number of studies have demonstrated positively neurorestorative effects of exosome-based therapy, which are largely mediated by the microRNA cargo. Herein, we review the current knowledge of exosomes, the relationships between exosomes and stroke, and the therapeutic effects of exosome-based treatments in neurovascular remodeling processes after stroke. Exosomes provide a viable and prospective treatment strategy for ischemic stroke patients.


2021 ◽  
Author(s):  
Qian Wang ◽  
Shu-Fang Zhao ◽  
Xia Xiao ◽  
Ya-Nan Liu ◽  
Xiu Li Wang ◽  
...  

Abstract Stroke remains a deadly and disabling disease with limited treatment tragedies due to the limitations of available treatments; novel therapies for stroke are needed. In this article, the synergistic results of dual bone marrow mesenchymal stem cells (BMSC) and fasudil treatment in rat models of ischemic stroke still requires further identification. Sprague-Dawley rats were used to construct the middle cerebral artery, occlusion models. BMSCs were incubated with fasudil, and MTT was performed to evaluate cell proliferation. The rats were treated with fasudil+BMSC, BMSC, fasudil, and saline. Blood samples were collected for complete blood count analysis and measurement of serum TNF-α levels. The neurological functions were evaluated. After the rats were sacrificed, immunohistochemical staining and TTC staining was performed. Fasudil promoted the proliferation of BMSCs and induced their differentiation into neuron-like cells. BMSCs increased the proportion of neutrophils; nevertheless, fasudil counteracted the neutrophil increase. The TUJ-1/MAP2/VIII factor expression in the fasudil+BMSC group was significantly higher than that in the other groups. The number of GFAP-positive cells decreased in the fasudil+BMSC and BMSC alone groups. The infarct volume in the fasudil+BMSC and BMSC alone groups was significantly lower than in the fasudil alone and control groups.Both BMSCs and fasudil exert neurorestorative effects in rat models of cerebral ischemia. Fasudil neutralizes the pro-inflammatory effects of BMSCs, while BMSCs and fasudil together had synergistic effects promoting neurovascular remodeling and neurological function recovery in stroke. A combination of BMSCs and fasudil provides a promising method for the treatment of ischemic stroke.


2021 ◽  
Vol 108 (Supplement_5) ◽  
Author(s):  
S Keni ◽  
C Smith ◽  
G Thompson ◽  
P M Brennan

Abstract Introduction The neurovascular unit (NVU) is implicated in glioma tumourigenesis and treatment resistance but intertumoural heterogeneity is not well characterised. We evaluated the structure of the glioma NVU across tumour grades, in primary and recurrent disease. We determined association to overall survival. Method Ethics approval was obtained (15/ES/0094). A tissue microarray was constructed using biopsies from 137 patients and was immunostained for endothelial cells (CD31), extracellular matrix (collagen-IV), pericytes (PDGFR-β and α-SMA) and tight junctions (claudin-V). The immunostaining was assessed using QuPath software and compared by one-way analysis of variance with Tukey post-hoc testing. Association to overall survival was by univariate Cox regression with hazard ratios (HR). Result Primary grade IV tumours had greater CD31+ than grade II tumours (P = 0.046) or recurrent tumours (P = 0.013). After normalising to CD31+, collagen-IV+ was greater in recurrent tumours than in primary grade IV tumours (P = 0.013). PDGFR-β+ was greater in primary grade II tumours than in primary grade III tumours (P = 0.002), primary grade IV tumours (P < 0.001) or recurrent tumours (P < 0.001). Normalised α-SMA+ was greater in recurrent tumours than in primary grade IV tumours (P = 0.021). CD31 + (HR: 1.028, P = 0.004) and collagen-IV + (HR: 1.014, P = 0.008) were negative prognostic factors. After normalisation, PDGFR-β + (HR: 0.975, P = 0.004), α-SMA + (HR: 0.971, P = 0.020) and claudin-V + (HR: 0.994, P = 0.021) were positive prognostic factors. Conclusion Neurovascular remodeling is a feature of malignancy and recurrent tumours have altered neurovascular phenotypes. Markers for pericytes, extracellular matrix and tight junctions supplement classical grading features and predict tumour behavior. Take-home Message Neurovascular remodeling is a feature of malignancy and recurrent tumours have altered neurovascular phenotypes. Markers for pericytes, extracellular matrix and tight junctions supplement classical grading features and predict tumour behavior.


Stroke ◽  
2021 ◽  
Vol 52 (Suppl_1) ◽  
Author(s):  
Xianshuang S LIU ◽  
Baoyan Fan ◽  
Chao Li ◽  
Albert Levin ◽  
Rui Lan Zhang ◽  
...  

Background: Adult neurogenesis facilitates brain remodeling after stroke. Exosomes derived from neural stem cells (NSCs) promote ischemic neurovascular remodeling including angiogenesis and axonal outgrowth, potentially by transferring their cargo proteins and miRNAs to recipient cells. However, cargo profiles of proteins and miRNAs in NSC exosomes have not been investigated. Methods: Exosomes were isolated from supernatants of cultured NSCs harvested from the subventricular zone of rats subjected to 7 day middle cerebral artery occlusion (MCAO) and non-MCAO rats, respectively. Mass spectrometry and miRNA array were utilized to determine the protein and miRNA profiles of NSC-derived exosomes (NSC-Exos). Bioinformatic pathway analyses were performed using Ingenuity Pathway Analysis (IPA). Results: Exosome markers and size distribution (50-200nm) were validated with Western blot, transmission electron microscopy and Nanosight measurements, respectively. Proteomics analysis yielded a total of 1,770 proteins in ischemic NSC-Exos. Bioinformatics analysis identified 24, 23 and 23 proteins that were related to neuronal cell proliferation, migration and differentiation, respectively. Intriguingly, enrichment signaling pathway analysis revealed cargo proteins in ischemic NSC-Exos were highly associated with dysfunction, membrane, and permeability of mitochondrion, indicating a critical role of extracellular mitochondrion in stroke-induced neurogenesis. In addition, 318 miRNAs were detected in ischemic NSC-Exos. Gene ontology analysis demonstrated that differentially expressed miRNAs between ischemic and non-ischemic NSC-Exos were highly related to inflammation, cell proliferation, cell cycle, and differentiation. The top 3 upregulated miRNAs including miR-106b, miR-542,miR-125b were validated in ischemic NSC-Exos using RT-PCR. The functions of these miRNAs are related to the induction of angiogenesis. Summary/Conclusion: Our results for the first time demonstrate that ischemic NSC-Exos contain a robust profile of protein and miRNA effectors, which may provide new insights into the function of NSC-Exos in stroke-induced neurogenesis and potentially lead to new therapeutic targets against stroke.


2020 ◽  
Vol 10 (6) ◽  
pp. 195-201
Author(s):  
Farah Fourcand ◽  
Ashish Kulhari ◽  
Siddhart Mehta ◽  
Haralabos Zacharatos ◽  
Amrinder Singh ◽  
...  

Purpose: The purpose of this study was to measure sensitivity of virtual reality (VR) in detecting biomarkers of neurovascular remodeling suboptimally evaluated in digital subtraction angiography (DSA) of treated unruptured, intracranial aneurysms. Methods: The sensitivity of virtual reality and digital subtraction angiography in detection of neurovascular biomarkers in aneurysms treated with flow diversion, coiling, and clipping were evaluated. Validated grading scales were integrated into a standardized rating platform. The respective novel and conceptual measures of minimal imaging important difference (MIID) and number needed to image (NNI) were calculated for each biomarker. Results: In flow diversion, coiling, and clipping, minimal imaging important difference and number needed to image were associated with virtual reality in detection of abnormal biomarkers, with the exception of stasis phase associated with digital subtraction angiography. Number needed to image was associated with flow diversion stent stenosis (RR: 7.00, 95% CI 0.37 to 131.97; OR: 7.46, 95% CI 0.38 to 148.49). Minimal imaging important difference was greatest in residual aneurysm filling (25%±66, 95% CI) in flow diversion and Meyer score in coiling (42.5%±17.69, 95% CI) and clipping (22.2%±13.58, 95% CI). Regression models demonstrated minimal imaging important difference and number needed to image shared a significant correlation (R20.99, 95% CI, p<0.001). Conclusion: Virtual reality adds value to digital subtraction angiography in evaluation of aneurysms treated with flow diversion, coiling, and clipping. Larger, prospective studies are warranted to increase statistical power and validate clinical significance.


2020 ◽  
Vol 27 (37) ◽  
pp. 6294-6305 ◽  
Author(s):  
Geir Bjørklund ◽  
Maryam Dadar ◽  
Jan Aaseth ◽  
Salvatore Chirumbolo

Thymosin Beta-4 (Tβ4) is known as a major pleiotropic actin-sequestering protein that is involved in tumorigenesis. Tβ4 is a water-soluble protein that has different promising clinical applications in the remodeling and ulcerated tissues repair following myocardial infarction, stroke, plasticity and neurovascular remodeling of the Peripheral Nervous System (PNS) and the Central Nervous System (CNS). On the other hand, similar effects have been observed for Tβ4 in other kinds of tissues, including cardiac muscle tissue. In recent reports, as it activates resident epicardial progenitor cells and modulates inflammatory-caused injuries, Tβ4 has been suggested as a promoter of the survival of cardiomyocytes. Furthermore, Tβ4 may act in skeletal muscle and different organs in association/synergism with numerous other tissue repair stimulating factors, including melatonin and C-fiber-derived peptides. For these reasons, the present review highlights the promising role of Tβ4 in cardiac healing.


2020 ◽  
Vol 381 (2) ◽  
pp. 379-379
Author(s):  
Analía Richeri ◽  
Gabriela Vierci ◽  
Gaby Fabiana Martínez ◽  
María Paula Latorre ◽  
Cora Chalar ◽  
...  

2020 ◽  
Vol 381 (2) ◽  
pp. 299-308 ◽  
Author(s):  
Analía Richeri ◽  
Gabriela Vierci ◽  
Gaby Fabiana Martínez ◽  
María Paula Latorre ◽  
Cora Chalar ◽  
...  

Stroke ◽  
2020 ◽  
Vol 51 (Suppl_1) ◽  
Author(s):  
Victoria L Wolf ◽  
Weiguo Li ◽  
Yasir Abdul ◽  
Guangkuo Dong ◽  
Rebecca Ward ◽  
...  

We have shown that 1) poor recovery in diabetes is associated with greater hemorrhagic transformation and significant loss of the cerebrovasculature, and 2) iron chelation therapy with deferoxamine (DFX) improves sensorimotor and cognitive outcomes while preventing vasoregression in male diabetic animals after stroke. This study tested the hypotheses that 1) diabetes mediates pathological post-stroke neovascularization in females and 2) DFX attenuates microglial activation and pathological neurovascular remodeling in both sexes. Control and diabetic animals were subjected to embolic middle cerebral artery occlusion (MCAO). DFX (100 mg/kg) or vehicle was given 1hour after MCAO and repeated every 12h for 7 days after stroke. Functional outcomes were assessed over time. Vascular indices, microglial morphology (activation), and neurovascular integrity (IgG and unpolarized Aquaporin-4) were measured at Day 14. Male and female microvascular endothelial cells (BMVECs) treated with iron and/or DFX were tested for viability and endothelial mesenchymal transition (EndMT) markers. DFX preserved vascular volume post-stroke in diabetic males. Stroke did not cause vasoregression in diabetic female animals; however, DFX reduced vascular indices while improving sensorimotor but not cognitive outcomes in both control and diabetic females. Ischemic injury amplified microglial activation and neurovascular remodeling in diabetes while DFX treatment restored these changes to control levels in male diabetic animals but not in females (Table). Female BMVECs grown under diabetic conditions expressed α-SMA and N-cadherin while VE-cadherin was decreased, indicative of EndMT (p<0.05 vs normal glucose). Data suggest that DFX treatment has sex- and disease-dependent effects on post-stroke neovascularization. Additional studies will aim to address the mechanisms by which DFX exerts these differential effects on functional outcomes and neurovascular remodeling.


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