PMID- 32169114
OWN - NLM
STAT- MEDLINE
DCOM- 20201102
LR  - 20201102
IS  - 2045-8118 (Electronic)
IS  - 2045-8118 (Linking)
VI  - 17
IP  - 1
DP  - 2020 Mar 14
TI  - Autophagy-mediated occludin degradation contributes to blood-brain barrier 
      disruption during ischemia in bEnd.3 brain endothelial cells and rat ischemic 
      stroke models.
PG  - 21
LID - 10.1186/s12987-020-00182-8 [doi]
LID - 21
AB  - BACKGROUND: The blood-brain barrier (BBB) maintains homeostasis of the brain 
      environment by tightly regulating the entry of substances from systemic 
      circulation. A breach in the BBB results in increased permeability to potentially 
      toxic substances and is an important contributor to amplification of ischemic 
      brain damage. The precise molecular pathways that result in impairment of BBB 
      integrity remain to be elucidated. Autophagy is a degradation pathway that clears 
      damaged or unnecessary proteins from cells. However, excessive autophagy can lead 
      to cellular dysfunction and death under pathological conditions. METHODS: In this 
      study, we investigated whether autophagy is involved in BBB disruption in 
      ischemia, using in vitro cells and in vivo rat models. We used brain endothelial 
      bEnd.3 cells and oxygen glucose deprivation (OGD) to simulate ischemia in 
      culture, along with a rat ischemic stroke model to evaluate the role of autophagy 
      in BBB disruption during cerebral ischemia. RESULTS: OGD 18 h induced cellular 
      dysfunction, and increased permeability with degradation of occludin and 
      activation of autophagy pathways in brain endothelial cells. Immunostaining 
      revealed that occludin degradation is co-localized with ischemic autophagosomes. 
      OGD-induced occludin degradation and permeability changes were significantly 
      decreased by inhibition of autophagy using 3-methyladenine (3-MA). Enhanced 
      autophagic activity and loss of occludin were also observed in brain capillaries 
      isolated from rats with middle cerebral artery occlusion (MCAO). Intravenous 
      administration of 3-MA inhibited these molecular changes in brain capillaries, 
      and recovered the increased permeability as determined using Evans blue. 
      CONCLUSIONS: Our findings provide evidence that autophagy plays an important role 
      in ischemia-induced occludin degradation and loss of BBB integrity.
FAU - Kim, Kyeong-A
AU  - Kim KA
AD  - College of Pharmacy Institute of Pharmaceutical Science and Technology, Hanyang 
      University, Ansan, Republic of Korea.
FAU - Kim, Donghyun
AU  - Kim D
AD  - College of Pharmacy Institute of Pharmaceutical Science and Technology, Hanyang 
      University, Ansan, Republic of Korea.
FAU - Kim, Jeong-Hyeon
AU  - Kim JH
AD  - College of Pharmacy Institute of Pharmaceutical Science and Technology, Hanyang 
      University, Ansan, Republic of Korea.
FAU - Shin, Young-Jun
AU  - Shin YJ
AD  - College of Pharmacy Institute of Pharmaceutical Science and Technology, Hanyang 
      University, Ansan, Republic of Korea.
FAU - Kim, Eun-Sun
AU  - Kim ES
AD  - College of Pharmacy Institute of Pharmaceutical Science and Technology, Hanyang 
      University, Ansan, Republic of Korea.
FAU - Akram, Muhammad
AU  - Akram M
AD  - College of Pharmacy Institute of Pharmaceutical Science and Technology, Hanyang 
      University, Ansan, Republic of Korea.
AD  - Faculty of Pharmacy, University of Sindh, Jamshoro, Pakistan.
FAU - Kim, Eun-Hye
AU  - Kim EH
AD  - College of Pharmacy Institute of Pharmaceutical Science and Technology, Hanyang 
      University, Ansan, Republic of Korea.
FAU - Majid, Arshad
AU  - Majid A
AD  - Sheffield Institute for Translational Neuroscience, University of Sheffield, 
      Sheffield, England, UK.
FAU - Baek, Seung-Hoon
AU  - Baek SH
AD  - College of Pharmacy and Research Institute of Pharmaceutical Science and 
      Technology (RIPST), Ajou University, Suwon, Republic of Korea.
FAU - Bae, Ok-Nam
AU  - Bae ON
AUID- ORCID: 0000-0003-0583-2116
AD  - College of Pharmacy Institute of Pharmaceutical Science and Technology, Hanyang 
      University, Ansan, Republic of Korea. onbae@hanyang.ac.kr.
LA  - eng
GR  - HI14C2284/Ministry of Health and Welfare/
GR  - NRF-2017R1C1B3002626/National Research Foundation of Korea/
PT  - Journal Article
DEP - 20200314
PL  - England
TA  - Fluids Barriers CNS
JT  - Fluids and barriers of the CNS
JID - 101553157
RN  - 0 (Occludin)
RN  - 0 (Ocln protein, rat)
SB  - IM
MH  - Animals
MH  - Autophagy/*physiology
MH  - Blood-Brain Barrier/*metabolism
MH  - Brain Ischemia/*metabolism
MH  - Cells, Cultured
MH  - Disease Models, Animal
MH  - Endothelial Cells/*metabolism
MH  - Infarction, Middle Cerebral Artery/metabolism
MH  - Occludin/*metabolism
MH  - Rats
MH  - Stroke/*metabolism
PMC - PMC7071658
OTO - NOTNLM
OT  - Autophagy
OT  - Blood-brain barrier (BBB)
OT  - Ischemic stroke
OT  - Middle cerebral artery occlusion (MCAO)
OT  - Occludin
OT  - Oxygen-glucose deprivation (OGD)
COIS- The authors declare that they have no competing interests.
EDAT- 2020/03/15 06:00
MHDA- 2020/11/03 06:00
PMCR- 2020/03/14
CRDT- 2020/03/15 06:00
PHST- 2019/11/22 00:00 [received]
PHST- 2020/03/03 00:00 [accepted]
PHST- 2020/03/15 06:00 [entrez]
PHST- 2020/03/15 06:00 [pubmed]
PHST- 2020/11/03 06:00 [medline]
PHST- 2020/03/14 00:00 [pmc-release]
AID - 10.1186/s12987-020-00182-8 [pii]
AID - 182 [pii]
AID - 10.1186/s12987-020-00182-8 [doi]
PST - epublish
SO  - Fluids Barriers CNS. 2020 Mar 14;17(1):21. doi: 10.1186/s12987-020-00182-8.