Neuroprotective effects of SMTP-44D in mice stroke model in relation to neurovascular unit and trophic coupling

Autor: Ryuta Morihara, Yong Huang, Toru Yamashita, Mami Takemoto, Nozomi Hishikawa, Koji Abe, Xia Liu, Keiji Hasumi, Yasuyuki Ohta, Kota Sato, Jingwei Shang, Eriko Suzuki, Tian Feng, Xiaowen Shi, Yumiko Nakano, Yusuke Fukui
Rok vydání: 2018
Předmět:
Brain Infarction
Male
0301 basic medicine
Apoptosis
Nerve Tissue Proteins
Tropomyosin receptor kinase B
Oxidative phosphorylation
Pharmacology
Neuroprotection
Acetylglucosamine
Mice
03 medical and health sciences
Cellular and Molecular Neuroscience
chemistry.chemical_compound
Stachybotrys
0302 clinical medicine
Fibrinolytic Agents
Phenols
Pyroptosis
Edaravone
Animals
Medicine
Stroke
Mice
Inbred ICR
biology
Caspase 3
Tumor Necrosis Factor-alpha
business.industry
Brain-Derived Neurotrophic Factor
Nitrotyrosine
Calcium-Binding Proteins
Microfilament Proteins
Nuclear Proteins
Infarction
Middle Cerebral Artery
Neurovascular bundle
medicine.disease
DNA-Binding Proteins
Oxidative Stress
Neuroprotective Agents
030104 developmental biology
chemistry
Tissue Plasminogen Activator
biology.protein
Blood Vessels
NeuN
business
030217 neurology & neurosurgery
Zdroj: Journal of Neuroscience Research. 96:1887-1899
ISSN: 0360-4012
Popis: Stachybotrys microspora triprenyl phenol (SMTP)-44D has both anti-oxidative and anti-inflammatory activities, but its efficacy has not been proved in relation to the pathological changes of neurovascular unit (NVU) and neurovascular trophic coupling (NVTC) in ischemic stroke. Here, the present study was designed to assess the efficacies of SMTP-44D, moreover, compared with the standard neuroprotective reagent edaravone in ischemic brains. ICR mice were subjected to transient middle cerebral artery occlusion (tMCAO) for 60 min, SMTP-44D (10 mg/kg) or edaravone (3 mg/kg) was intravenously administrated through subclavian vein just after the reperfusion, and these mice were examined at 1, 3, and 7 d after reperfusion. Compared with the vehicle group, SMTP-44D treatment revealed obvious ameliorations in clinical scores and infarct volume, meanwhile, markedly suppressed the accumulations of 4-HNE, 8-OHdG, nitrotyrosine, RAGE, TNF-α, Iba-1, and cleaved caspase-3 after tMCAO. In addition, SMTP-44D significantly prevented the dissociation of NVU and improved the intensity of NAGO/BDNF and the number of BDNF/TrkB and BDNF/NeuN double positive cells. These effects of SMTP-44D in reducing oxidative and inflammatory stresses were similar to or stronger than those of edaravone. The present study demonstrated that SMTP-44D showed strong anti-oxidative, anti-inflammatory, and anti-apoptotic effects, moreover, the drug also significantly improved the NVU damage and NVTC in the ischemic brain.
Databáze: OpenAIRE
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