Phosphorylated recombinant HSP27 protects the brain and attenuates blood-brain barrier disruption following stroke in mice receiving intravenous tissue-plasminogen activator
| العنوان: | Phosphorylated recombinant HSP27 protects the brain and attenuates blood-brain barrier disruption following stroke in mice receiving intravenous tissue-plasminogen activator |
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| المؤلفون: | Yasuo Uchiyama, Kazuo Yamashiro, Ryota Tanaka, Yoshiaki Shimada, Nobutaka Hattori, Masato Koike, Takao Urabe, Hideki Shimura |
| المصدر: | PLoS ONE PLoS ONE, Vol 13, Iss 5, p e0198039 (2018) |
| بيانات النشر: | Public Library of Science, 2018. |
| سنة النشر: | 2018 |
| مصطلحات موضوعية: | 0301 basic medicine, Male, Critical Care and Emergency Medicine, Infarction, lcsh:Medicine, Pharmacology, Pathology and Laboratory Medicine, Vascular Medicine, Epithelium, Brain Ischemia, Mice, 0302 clinical medicine, Animal Cells, Medicine and Health Sciences, Medicine, Edema, Brain Damage, Phosphorylation, lcsh:Science, Stroke, Microvessel, Heat-Shock Proteins, Cerebral Ischemia, Multidisciplinary, biology, Infarction, Middle Cerebral Artery, Extravasation, Recombinant Proteins, Neoplasm Proteins, Endothelial stem cell, Hemorrhagic Stroke, Neuroprotective Agents, Neurology, Blood-Brain Barrier, Tissue Plasminogen Activator, Injections, Intravenous, medicine.symptom, Cellular Types, Anatomy, Research Article, Cerebrovascular Diseases, Hemorrhage, Brain damage, 03 medical and health sciences, Signs and Symptoms, Hsp27, Diagnostic Medicine, Heat shock protein, Animals, Ischemic Stroke, business.industry, lcsh:R, Biology and Life Sciences, Endothelial Cells, Epithelial Cells, Cell Biology, medicine.disease, Mice, Inbred C57BL, 030104 developmental biology, Biological Tissue, Reperfusion, biology.protein, lcsh:Q, business, 030217 neurology & neurosurgery, Molecular Chaperones |
| الوصف: | Loss of integrity of the blood-brain barrier (BBB) in ischemic stroke victims initiates a devastating cascade of events causing brain damage. Maintaining the BBB is important to preserve brain function in ischemic stroke. Unfortunately, recombinant tissue plasminogen activator (tPA), the only effective fibrinolytic treatment at the acute stage of ischemic stroke, also injures the BBB and increases the risk of brain edema and secondary hemorrhagic transformation. Thus, it is important to identify compounds that maintain BBB integrity in the face of ischemic injury in patients with stroke. We previously demonstrated that intravenously injected phosphorylated recombinant heat shock protein 27 (prHSP27) protects the brains of mice with transient middle cerebral artery occlusion (tMCAO), an animal stroke-model. Here, we determined whether prHSP27, in addition to attenuating brain injury, also decreases BBB damage in hyperglycemic tMCAO mice that had received tPA. After induction of hyperglycemia and tMCAO, we examined 4 treatment groups: 1) bovine serum albumin (BSA), 2) prHSP27, 3) tPA, 4) tPA plus prHSP27. We examined the effects of prHSP27 by comparing the BSA and prHSP27 groups and the tPA and tPA plus prHSP27 groups. Twenty-four hours after injection, prHSP27 reduced infarct volume, brain swelling, neurological deficits, the loss of microvessel proteins and endothelial cell walls, and mortality. It also reduced the rates of hemorrhagic transformation, extravasation of endogenous IgG, and MMP-9 activity, signs of BBB damage. Therefore, prHSP27 injection attenuated brain damage and preserved the BBB in tPA-injected, hyperglycemic tMCAO experimental stroke-model mice, in which the BBB is even more severely damaged than in simple tMCAO mice. The attenuation of brain damage and BBB disruption in the presence of tPA suggests the effectiveness of prHSP27 and tPA as a combination therapy. prHSP27 may be a novel therapeutic agent for ischemic stroke patients whose BBBs are injured following tPA injections. |
| اللغة: | English |
| تدمد: | 1932-6203 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::dba7c23bf659d8d5c9493f8be0c9cdceTest http://europepmc.org/articles/PMC5993064Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....dba7c23bf659d8d5c9493f8be0c9cdce |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 19326203 |
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