Vascular PDGFR-alpha protects against BBB dysfunction after stroke in mice

AbstractBlood –brain barrier (BBB) dysfunction underlies the pathogenesis of many neurological diseases. Platelet-derived growth factor receptor-alpha (PDGFRα) induces hemorrhagic transformation (HT) downstream of tissue plasminogen activator in thrombolytic therapy of acute stroke. Thus, PDGFs are attractive therapeutic targets for BBB dysfunction. In the present study, we examined the role of PDGF signaling in the process of tissue remodeling after middle cerebral arterial occlusion (MCAO) in mice. Firstly, we found that imatinib increased lesion size after permanent MCAO in wild-type mice. Moreover, i matinib-induced HT only when administrated in the subacute phase of MCAO, but not in the acute phase. Secondly, we generated genetically mutated mice (C-KO mice) that showed decreased expression of perivascular PDGFRα. Additionally, transient MCAO experiments were performed in these mice. We found that the ischemic lesion size was not affected; however, the recruitment of PDGFRα/type I collagen-expressing perivascular cells was significantly downregulated, and HT and IgG leakage was augmented only in the subacute phase of stroke in C-KO mice. In both experiments, we found that the expression of tight junction proteins and PDGFRβ-expressing pericyte coverage was not significantly affected in imatinib-treated mice and in C-KO mice. The specific implication of PDGFRα signaling was suggestive of protective effects against BBB dysfunction during ...
Source: Angiogenesis - Category: Molecular Biology Source Type: research

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Conclusions: Lower serum magnesium levels in patients with ischemic stroke are associated with an increased risk of HT after intravenous thrombolysis, but perhaps only when serum magnesium is below a certain minimal concentration.
Source: Frontiers in Neurology - Category: Neurology Source Type: research
Conclusion: In our cohort, blood ADAMTS13 antigen level before rt-PA therapy could not be used as an independent biomarker in predicting clinical outcomes of AIS patients at 90 days.
Source: Frontiers in Neurology - Category: Neurology Source Type: research
CONCLUSION: The new IHS protocol has led to a marked increase in cases identified, rapid evaluation, and high utilization rate of acute stroke therapies.
Source: Journal of Neuroscience Nursing - Category: Neuroscience Tags: Clinical Nursing Focus Source Type: research
AbstractIntracerebral hemorrhage is the most dangerous complication in tPA thrombolytic therapy for ischemic stroke, which occurs as a consequence of endothelial cell death at the blood brain barrier (BBB) during thrombolytic reperfusion. We have previously shown that cerebral ischemia induced rapid occludin degradation and BBB disruption. Here we demonstrated an important role of occludin degradation in facilitating the evolution of ischemic endothelial cells towards death. Cultured brain microvascular endothelial cells (bEnd.3 cells) were exposed to oxygen ‐glucose deprivation (OGD) or incubated with occludin siRNA or ...
Source: Journal of Neurochemistry - Category: Neuroscience Authors: Tags: ORIGINAL ARTICLE Source Type: research
This study aimed to assess the relationship between baseline SBP and outcome. Materials and Methods: Studies that evaluated the association between the baseline SBP and the outcome of patients undergoing thrombolytic therapy were sought. Data were extracted according to a predefined data extraction form and then analyzed by STATA 12.0 software. The primary endpoint was the occurrence of good outcomes measured by a modified Rankin Scale score at 3 months, while the secondary endpoint was the occurrence of intracranial hemorrhage and death. Results: Eleven studies involving a total of 33,263 patients were included. Poo...
Source: The Neurologist - Category: Neurology Tags: Original Articles Source Type: research
Abstract Thrombolytic therapy with recombinant tissue plasminogen activator (rtPA) in ischaemic stroke has been associated with neurotoxicity, blood brain barrier (BBB) disruption and intra-cerebral hemorrhage. To examine rtPA cellular toxicity we investigated the effects of rtPA on cell viability in neuronal, astrocyte and brain endothelial cell (bEnd.3) cultures with and without prior exposure to oxygen-glucose deprivation (OGD). In addition, the neuroprotective peptide poly-arginine-18 (R18D; 18-mer of D-arginine) was examined for its ability to reduce rtPA toxicity. Studies demonstrated that a 4- or 24-h expos...
Source: Neurochemical Research - Category: Neuroscience Authors: Tags: Neurochem Res Source Type: research
eng Tsong-Hai Lee Ischemic stroke is the most common type of stroke, and early interventional treatment is associated with favorable outcomes. In the guidelines, thrombolytic therapy using recombinant tissue-type plasminogen activator (rt-PA) is recommended for eligible patients with acute ischemic stroke. However, the risk of hemorrhagic complications limits the use of rt-PA, and the risk factors for poor treatment outcomes need to be identified. To identify the risk factors associated with in-hospital poor outcomes in patients treated with rt-PA, we analyzed the electronic medical records of patients who were diagn...
Source: International Journal of Environmental Research and Public Health - Category: Environmental Health Authors: Tags: Article Source Type: research
Patients who present emergently with focal neurological deficits concerning for acute ischemic stroke can be extremely challenging to diagnose and treat. Unnecessary administration of thrombolytics to potential stroke patients whose symptoms are not caused by an acute ischemic stroke —stroke mimics—may result in patient harm, although the overall risk of hemorrhagic complications among stroke mimics is low.
Source: The Journal of Emergency Medicine - Category: Emergency Medicine Authors: Tags: Clinical Communications: Adult Source Type: research
CONCLUSIONS: RSG treatment protects against BBB damage and ameliorates HT in delayed tPA-treated stroke mice by activating PPAR-γ and favoring microglial polarization toward anti-inflammatory phenotype. PMID: 31756041 [PubMed - as supplied by publisher]
Source: CNS Neuroscience and Therapeutics - Category: Neuroscience Authors: Tags: CNS Neurosci Ther Source Type: research
AbstractPatients with atrial fibrillation (AF) who suffer an acute ischemic stroke are at risk for both hemorrhagic transformation and recurrent ischemic stroke in the acute post ‐stroke period. Oral anticoagulants are recommended for secondary stroke prevention in patients with AF. The optimal time to initiate anticoagulant therapy after acute ischemic stroke in patients with AF is uncertain. There is concern that early initiation increases the risk of hemorrhagic transfo rmation, whereas delayed initiation leaves the patient at risk for recurrent ischemic stroke. In this article, we provide a review of the risk of hemo...
Source: Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy - Category: Drugs & Pharmacology Authors: Tags: REVIEW OF THERAPEUTICS Source Type: research
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