PMID- 32738431
OWN - NLM
STAT- MEDLINE
DCOM- 20210514
LR  - 20220531
IS  - 1873-7544 (Electronic)
IS  - 0306-4522 (Linking)
VI  - 443
DP  - 2020 Sep 1
TI  - The Mitochondria-targeted Peptide, Bendavia, Attenuated 
      Ischemia/Reperfusion-induced Stroke Damage.
PG  - 110-119
LID - S0306-4522(20)30485-1 [pii]
LID - 10.1016/j.neuroscience.2020.07.044 [doi]
AB  - After ischemic stroke, oxygen and nutrition depletion induce mitochondrial 
      dysfunction, which aggravates brain injury. Bendavia, a mitochondria-targeted 
      tetra-peptide, has anti-oxidative and anti-inflammatory activities. We previously 
      reported that bendavia protected human brain microvascular endothelial cells 
      against oxygen/glucose deprivation (OGD)-induced damage via preserving 
      mitochondrial function. The effects of bendavia on mitochondrial function include 
      the inhibition of reactive oxygen species (ROS) production, inhibition of 
      apoptosis, and restoration of adenosine tri-phosphate synthesis. However, the 
      influence of bendavia on the blood-brain barrier (BBB) and neurons after brain 
      ischemia/reperfusion damage is unclear. The aim of this study was to investigate 
      whether bendavia has protective effects against ischemia/reperfusion damage using 
      both in vivo and in vitro models. The in vivo experiments were conducted in mice, 
      which were subjected to transient middle cerebral occlusion (t-MCAO) to induce 
      brain ischemia/reperfusion damage. After t-MCAO, the cerebral blood flow (CBF), 
      neurological deficits, infarct volume, BBB permeability, and microglia/macrophage 
      activation were assessed. Compared to the vehicle group, bendavia administration 
      (administered twice; immediately after reperfusion and 4 h later) attenuated the 
      sensori-motor dysfunction and infarct formation independent of CBF variation. In 
      addition, bendavia decreased BBB hyper-permeability and microglia/macrophage 
      activation. The in vitro experiments were conducted utilizing two models: (1) 
      OGD/re-oxygenation (OGD/R) or (2) hydrogen peroxide (H(2)O(2))-induced neuron 
      damage. In both models, bendavia inhibited neuronal cell death induced by OGD/R 
      or H(2)O(2). These findings indicated that bendavia attenuated brain 
      ischemia/reperfusion damage and has direct neuroprotective effects against cell 
      injury. Therefore, bendavia may be a novel therapeutic agent to improve ischemic 
      stroke patient outcome.
CI  - Copyright (c) 2020 IBRO. Published by Elsevier Ltd. All rights reserved.
FAU - Imai, Takahiko
AU  - Imai T
AD  - Molecular Pharmacology, Department of Biofunctional Evaluation, Gifu 
      Pharmaceutical University, Gifu 501-1196, Japan.
FAU - Matsubara, Hirofumi
AU  - Matsubara H
AD  - Molecular Pharmacology, Department of Biofunctional Evaluation, Gifu 
      Pharmaceutical University, Gifu 501-1196, Japan; Department of Neurosurgery, 
      School of Medicine, Gifu University, Gifu 501-1194, Japan.
FAU - Nakamura, Shinsuke
AU  - Nakamura S
AD  - Molecular Pharmacology, Department of Biofunctional Evaluation, Gifu 
      Pharmaceutical University, Gifu 501-1196, Japan.
FAU - Hara, Hideaki
AU  - Hara H
AD  - Molecular Pharmacology, Department of Biofunctional Evaluation, Gifu 
      Pharmaceutical University, Gifu 501-1196, Japan.
FAU - Shimazawa, Masamitsu
AU  - Shimazawa M
AD  - Molecular Pharmacology, Department of Biofunctional Evaluation, Gifu 
      Pharmaceutical University, Gifu 501-1196, Japan. Electronic address: 
      shimazawa@gifu-pu.ac.jp.
LA  - eng
PT  - Journal Article
DEP - 20200730
PL  - United States
TA  - Neuroscience
JT  - Neuroscience
JID - 7605074
RN  - 0 (Neuroprotective Agents)
RN  - 0 (Oligopeptides)
RN  - 0 (arginyl-2,'6'-dimethyltyrosyl-lysyl-phenylalaninamide)
RN  - BBX060AN9V (Hydrogen Peroxide)
SB  - IM
MH  - Animals
MH  - *Brain Ischemia/drug therapy
MH  - Endothelial Cells
MH  - Hydrogen Peroxide
MH  - Ischemia
MH  - Mice
MH  - Mitochondria
MH  - *Neuroprotective Agents/pharmacology
MH  - Oligopeptides
MH  - Reperfusion
MH  - *Reperfusion Injury/drug therapy
MH  - *Stroke
OTO - NOTNLM
OT  - bendavia
OT  - blood-brain barrier
OT  - brain ischemia
OT  - microglia/macrophage
OT  - neuron
OT  - oxygen-glucose deprivation/re-oxygenation (OGD/R)
EDAT- 2020/08/02 06:00
MHDA- 2021/05/15 06:00
CRDT- 2020/08/02 06:00
PHST- 2020/05/21 00:00 [received]
PHST- 2020/07/21 00:00 [revised]
PHST- 2020/07/22 00:00 [accepted]
PHST- 2020/08/02 06:00 [pubmed]
PHST- 2021/05/15 06:00 [medline]
PHST- 2020/08/02 06:00 [entrez]
AID - S0306-4522(20)30485-1 [pii]
AID - 10.1016/j.neuroscience.2020.07.044 [doi]
PST - ppublish
SO  - Neuroscience. 2020 Sep 1;443:110-119. doi: 10.1016/j.neuroscience.2020.07.044. 
      Epub 2020 Jul 30.