Differentiation independent neuroprotective role of Vcan+ oligodendrocyte precursor cells in Post-stroke cognitive impairment recovery
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE171393 | GEO | 2023/04/02
REPOSITORIES: GEO
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Project description:Differentiation independent neuroprotective role of Vcan+ oligodendrocyte precursor cells in Post-stroke cognitive impairment recovery
| PRJNA719379 | ENA
Project description:Ischemic-induced white matter injury is strongly correlated with the poor neurological outcomes in stroke patients. The transplantation of oligodendrocyte precursor cells (OPCs) is an effective candidate for enhancing re-myelination in congenitally dysmyelinated brain and spinal cord. Nevertheless, mechanisms governing the recovery of white matter and axon after OPCs transplantation are incompletely understood in ischemic stroke. In this study, OPCs were transplanted into the ischemic brain at 7 days after transient middle cerebral artery occlusion (tMCAO). We observed improved behavior recovery and reduced brain atrophy volume at 28 days after OPCs transplantation. Moreover, our results identified that myelin sheath integrity and endogenous OPCs proliferation and migration were promoted after OPCs transplantation. By contrast, AMD3100, an antagonist of C-X-C chemokine receptor type 4, eliminated the beneficial effects of OPCs transplantation on white matter integrity and endogenous oligodendrogenesis. In addition, the improvement of neurite growth and synaptogenesis after OPCs transplantation in ischemic brain or OPC co-cultured neurons, potentially through the upregulation of Netrin-1, was indicated by increased protein levels of synaptophysin and postsynaptic density protein 95. Knockdown of Deleted in Colorectal Carcinoma, a receptor of Netrin-1, prevented increased neurite growth and synaptogenesis in neurons co-cultured with OPCs. In conclusion, our studies suggested that engrafted OPCs promoted the recovery after ischemic stroke by enhancing endogenous oligodendrogenesis, neurite growth, and synaptogenesis; the last two being mediated by the Netrin-1/DCC axis.
| S-EPMC8612617 | biostudies-literature
Project description:Background:Oxidative damage may contribute to post-stroke cognitive impairment (PSCI), but the underlying mechanisms are not fully elucidated. Dimethyl fumarate (DMF) has been used as an antioxidant in multiple sclerosis and psoriasis patients. We hypothesized that redox state was associated with PSCI, and DMF might exert neuroprotective effect against PSCI via anti-oxidative actions. Methods:To confirm this hypothesis, we first conducted a clinical study (NCT03519828) that enrolled patients diagnosed with acute ischemic stroke within 48 hours. Data were analyzed based on demographic characteristics, disease history, clinical data and redox state. Logistic regression was used to identify the factors associated with PSCI. Next, a middle cerebral artery occlusion (MCAO) rat model was used to explore the antioxidant capacity and neuroprotective effect of DMF. Furthermore, behavioural experiments, histology and immunostaining, and transmission electron microscopy were also performed. Results:Higher baseline NIHSS score, lower GSH/GSSG and T-AOC levels were found in the PSCI patients. Better performance in Morris water maze and shuttle box testing, more regular arranged neurons and Nissl bodies, less TUNEL-positive cells and autophagosomes, lower expression of 4-HNE, and higher expression of GCLM and NQO1 were found in the (DMF + MCAO) rats compared with the MCAO rats. Conclusions:These findings suggest that DMF may alleviate PSCI via neuroprotective actions, providing a new therapeutic strategy for PSCI.
| S-EPMC7186746 | biostudies-literature
Project description:Perinatal white matter injury, or periventricular leukomalacia (PVL), is the most common cause of brain injury in premature infants and is the leading cause of cerebral palsy. Despite increasing numbers of surviving extreme premature infants and associated long-term neurological morbidity, our understanding and treatment of PVL remains incomplete. Inflammation- or ischemia/hypoxia-based rodent models, although immensely valuable, are largely restricted to reproducing short-term features of up to 3 weeks after injury. Given the long-term sequelae of PVL, there is a need for subchronic models that will enable testing of putative neuroprotective therapies. Here, we report long term characterization of a neonatal inflammation-induced rat model of PVL. We show bilateral ventriculomegaly, inflammation, reactive astrogliosis, injury to pre-oligodendrocytes, and neuronal loss 8 weeks after injury. We demonstrate neuroprotective effects of oligodendrocyte precursor cell transplantation. Our findings present a subchronic model of PVL and highlight the tissue protective effects of oligodendrocyte precursor cell transplants that demonstrate the potential of cell-based therapy for PVL.
| S-EPMC2789608 | biostudies-literature
Project description:Background and objectives: Little is known about the effect of osteoporosis on cognitive function in the acute and recovery phases of stroke. Early bone mineral density assessments during acute stroke may be a useful marker of cognitive function. We evaluated the effect of osteoporosis on cognitive function at the early and recovery phase of ischemic stroke in patients aged >50 years. Materials and Methods: We retrospectively examined consecutive patients with acute stroke hospitalized between 2016 and 2018. Osteoporosis was defined as a T-score <-2.5 for the femoral neck or lumbar spine bone mineral density. The primary outcome was cognitive impairment measured by the Korean Mini-Mental State Examination in the acute phase and recovery phase of ischemic stroke. Results: Of the 260 included subjects (107 men and 153 women), 70 (26.9%) had osteoporosis. Cognitive impairment was more severe in the osteoporosis group than in the non-osteoporosis group (30.5% versus 47.1%, p = 0.001). After the recovery phase of stroke, the proportion of patients with cognitive impairment remained higher in the osteoporosis group. The multivariate analysis revealed a correlation between a low femoral neck bone mineral density and severe cognitive impairment in the acute and recovery phases of stroke (adjusted odds ratio (OR) 4.09, 95% confidence interval (CI) 1.11-15.14 in the acute phase, and adjusted OR 11.17, 95% CI 1.12-110.98 in the recovery phase). Conclusions: Low bone mineral density is associated with poor cognitive function in the acute and recovery phases of stroke.
| S-EPMC7353884 | biostudies-literature
Project description:Cerebral small vessel disease is characterised by decreased cerebral blood flow and blood-brain barrier impairments which play a key role in the development of white matter lesions. We hypothesised that cerebral hypoperfusion causes local hypoxia, affecting oligodendrocyte precursor cell-endothelial cell signalling leading to blood-brain barrier dysfunction as an early mechanism for the development of white matter lesions. Bilateral carotid artery stenosis was used as a mouse model for cerebral hypoperfusion. Pimonidazole, a hypoxic cell marker, was injected prior to humane sacrifice at day 7. Myelin content, vascular density, blood-brain barrier leakages, and hypoxic cell density were quantified. Primary mouse oligodendrocyte precursor cells were exposed to hypoxia and RNA sequencing was performed. Vegfa gene expression and protein secretion was examined in an oligodendrocyte precursor cell line exposed to hypoxia. Additionally, human blood plasma VEGFA levels were measured and correlated to blood-brain barrier permeability in normal-appearing white matter and white matter lesions of cerebral small vessel disease patients and controls. Cerebral blood flow was reduced in the stenosis mice, with an increase in hypoxic cell number and blood-brain barrier leakages in the cortical areas but no changes in myelin content or vascular density. Vegfa upregulation was identified in hypoxic oligodendrocyte precursor cells, which was mediated via Hif1α and Epas1. In humans, VEGFA plasma levels were increased in patients versus controls. VEGFA plasma levels were associated with increased blood-brain barrier permeability in normal appearing white matter of patients. Cerebral hypoperfusion mediates hypoxia induced VEGFA expression in oligodendrocyte precursor cells through Hif1α/Epas1 signalling. VEGFA could in turn increase BBB permeability. In humans, increased VEGFA plasma levels in cerebral small vessel disease patients were associated with increased blood-brain barrier permeability in the normal appearing white matter. Our results support a role of VEGFA expression in cerebral hypoperfusion as seen in cerebral small vessel disease.
| S-EPMC10405482 | biostudies-literature
Project description:Acute ischemic stroke (AIS) is a global health burden and cognitive impairment is one of its most serious complication. Adequate interventions for AIS may have the potential to improve cognitive outcomes. In the present study, we selected Erigeron breviscapus (Vaniot) Hand.-Mazz. injection (Dengzhanxixin injection, DZXI), a widely used Chinese herbal injection, in contrast to edaravone as the positive control drug to test its potential to ameliorates neurological and cognitive impairments caused by AIS. We performed a 2-week randomized trial with these two drugs in AIS patients presenting mild to moderate cognitive impairments. Neuropsychological tests and MRI examinations showed that DZXI attenuated the neurological and cognitive impairments of patients and protected the grey matter in specific regions from ischemic damage. Notably, DZXI exerted better effects than edaravone in some neuropsychological tests, probably due to the protective effect of DZXI on grey matter. To explore the therapeutic mechanisms, we carried out an experiment with a middle cerebral artery occlusion rat model. We found that DZXI decreased the infarct volume and increased the survival of neuronal cells in the ischemic penumbra; furthermore, DZXI modulated the mitochondrial respiratory chain process and preserved the mitochondrial structure in the brain tissue. Overall, our data suggested that the administration of DZXI is effective at ameliorating neurological and cognitive impairments in AIS, and the underlying mechanisms are related to the protective effects of DZXI on cerebral neurons and neuronal mitochondria.
| S-EPMC8435665 | biostudies-literature
Project description:Cognitive decline is often present in stroke survivors, with a significant impact on motor recovery. However, how specific cognitive domains could impact motor recovery after robotic rehabilitation in patients with stroke is still not well understood. In this study, we analyzed the relationship between cognitive impairment and the outcome of a robot-mediated upper limb rehabilitation intervention in a sample of 51 subacute stroke patients. Participants were enrolled and treated with a set of robotic and sensor-based devices. Before the intervention, patients underwent a cognitive assessment by means of the Oxford Cognitive Screen. To assess the effect of the 30-session rehabilitation intervention, patients were assessed twice with the following outcome measures: the Fugl-Meyer Assessment for Upper Extremity (FMA-UE), to evaluate motor function; the Upper limb Motricity Index (MI), to evaluate upper limb muscle strength; the Modified Barthel Index (mBI), to evaluate activities of daily living and mobility. We found that deficits in spatial attention and executive functions impacted the mBI improvement, while language, number processing, and spatial attention deficits reduced the gains in the FMA-UE. These results suggest the importance to evaluate the cognitive functions using an adequate tool in patients with stroke undergoing a robotic rehabilitation intervention.
| S-EPMC8147141 | biostudies-literature
Project description:The strains, C57BL6/J, C3H/HeJ, and WSB/EiJ, show a similar collateral vessel anatomy but differ infarct volume after ischemic stroke induction. To identify a gene(s) exhibiting differential gene expression, we performed RNA seq experiment within these mouse strains.
2021-03-06 | GSE168383 | GEO
Project description:The global burden of ischaemic strokes is almost 4-fold greater than haemorrhagic strokes. Current evidence suggests that 25-30% of ischaemic stroke survivors develop immediate or delayed vascular cognitive impairment (VCI) or vascular dementia (VaD). Dementia after stroke injury may encompass all types of cognitive disorders. States of cognitive dysfunction before the index stroke are described under the umbrella of pre-stroke dementia, which may entail vascular changes as well as insidious neurodegenerative processes. Risk factors for cognitive impairment and dementia after stroke are multifactorial including older age, family history, genetic variants, low educational status, vascular comorbidities, prior transient ischaemic attack or recurrent stroke and depressive illness. Neuroimaging determinants of dementia after stroke comprise silent brain infarcts, white matter changes, lacunar infarcts and medial temporal lobe atrophy. Until recently, the neuropathology of dementia after stroke was poorly defined. Most of post-stroke dementia is consistent with VaD involving multiple substrates. Microinfarction, microvascular changes related to blood-brain barrier damage, focal neuronal atrophy and low burden of co-existing neurodegenerative pathology appear key substrates of dementia after stroke injury. The elucidation of mechanisms of dementia after stroke injury will enable establishment of effective strategy for symptomatic relief and prevention. Controlling vascular disease risk factors is essential to reduce the burden of cognitive dysfunction after stroke. This article is part of a Special Issue entitled: Vascular Contributions to Cognitive Impairment and Dementia edited by M. Paul Murphy, Roderick A. Corriveau and Donna M. Wilcock.
| S-EPMC4827373 | biostudies-literature