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

Xiaowen Shi, Yasuyuki Ohta, Jingwei Shang, Ryuta Morihara, Yumiko Nakano, Yusuke Fukui, Xia Liu, Tian Feng, Yong Huang, Kota Sato, Mami Takemoto, Nozomi Hishikawa, Toru Yamashita, Eriko Suzuki, Keiji Hasumi, Koji Abe

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

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.

Original languageEnglish
JournalJournal of Neuroscience Research
DOIs
Publication statusAccepted/In press - Jan 1 2018

Fingerprint

Stachybotrys
Microsporidia
Neuroprotective Agents
Phenol
Stroke
Brain-Derived Neurotrophic Factor
Middle Cerebral Artery Infarction
Reperfusion
Anti-Inflammatory Agents
Subclavian Vein
Inbred ICR Mouse
Brain
Caspase 3
Oxidative Stress

Keywords

  • apoptosis
  • inflammatory
  • neurovascular trophic coupling
  • neurovascular unit
  • oxidative
  • SMTP-44D
  • transient middle cerebral artery occlusion

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience

Cite this

Neuroprotective effects of SMTP-44D in mice stroke model in relation to neurovascular unit and trophic coupling. / Shi, Xiaowen; Ohta, Yasuyuki; Shang, Jingwei; Morihara, Ryuta; Nakano, Yumiko; Fukui, Yusuke; Liu, Xia; Feng, Tian; Huang, Yong; Sato, Kota; Takemoto, Mami; Hishikawa, Nozomi; Yamashita, Toru; Suzuki, Eriko; Hasumi, Keiji; Abe, Koji.

In: Journal of Neuroscience Research, 01.01.2018.

Research output: Contribution to journalArticle

Shi, Xiaowen ; Ohta, Yasuyuki ; Shang, Jingwei ; Morihara, Ryuta ; Nakano, Yumiko ; Fukui, Yusuke ; Liu, Xia ; Feng, Tian ; Huang, Yong ; Sato, Kota ; Takemoto, Mami ; Hishikawa, Nozomi ; Yamashita, Toru ; Suzuki, Eriko ; Hasumi, Keiji ; Abe, Koji. / Neuroprotective effects of SMTP-44D in mice stroke model in relation to neurovascular unit and trophic coupling. In: Journal of Neuroscience Research. 2018.
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AU - Shi, Xiaowen

AU - Ohta, Yasuyuki

AU - Shang, Jingwei

AU - Morihara, Ryuta

AU - Nakano, Yumiko

AU - Fukui, Yusuke

AU - Liu, Xia

AU - Feng, Tian

AU - Huang, Yong

AU - Sato, Kota

AU - Takemoto, Mami

AU - Hishikawa, Nozomi

AU - Yamashita, Toru

AU - Suzuki, Eriko

AU - Hasumi, Keiji

AU - Abe, Koji

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AB - 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.

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