PMID- 36509234
OWN - NLM
STAT- MEDLINE
DCOM- 20230202
LR  - 20240102
IS  - 1872-9754 (Electronic)
IS  - 0197-0186 (Print)
IS  - 0197-0186 (Linking)
VI  - 162
DP  - 2023 Jan
TI  - Cerebral microvascular matrix metalloproteinase-3 (MMP3) contributes to vascular 
      injury after stroke in female diabetic rats.
PG  - 105462
LID - S0197-0186(22)00187-5 [pii]
LID - 10.1016/j.neuint.2022.105462 [doi]
AB  - Diabetes exacerbates hemorrhagic transformation (HT) after stroke and worsens 
      clinical outcomes. Female patients with diabetes are at a greater risk of stroke 
      and worsened recovery. We have shown that activation of matrix metalloprotease 3 
      (MMP3) in hyperglycemic settings mediates HT in male rats. In light of our recent 
      findings that diabetic female rats develop greater HT, the current study was 
      designed to test the hypotheses that: 1) cerebral microvascular MMP3 activation 
      contributes to poor functional outcomes and increased hemorrhagic transformations 
      (HT) after ischemic stroke, and 2) MMP3 inhibition can improve functional 
      outcomes in female diabetic rats. Female control and diabetic Wistar rats were 
      subjected to 60 min of middle cerebral artery occlusion (MCAO). One cohort of 
      diabetic animals received a single dose of MMP3 inhibitor (UK356618; 15 mg/kg; 
      iv) or vehicle after reperfusion. Neurobehavioral outcomes, brain infarct size, 
      edema, HT, and MMPs were measured in brain tissue. Diabetic rats had significant 
      neurological deficits on Day 3 after stroke. MMP3 expression and enzyme activity 
      were significantly increased in both micro and macro vessels of diabetic animals. 
      MMP3 inhibition improved functional outcomes and reduced brain edema and HT 
      scores. In conclusion, cerebral endothelial MMP3 activation to vascular injury in 
      female diabetic rats. Our findings identify MMP3 as a potential therapeutic 
      target in diabetic stroke.
CI  - Published by Elsevier Ltd.
FAU - Abdul, Yasir
AU  - Abdul Y
AD  - Department of Pathology & Laboratory Medicine, Medical University of South 
      Carolina, USA; Ralph H. Johnson Veterans Affairs Health Care System, Charleston, 
      SC, USA.
FAU - Jamil, Sarah
AU  - Jamil S
AD  - Department of Pathology & Laboratory Medicine, Medical University of South 
      Carolina, USA; Ralph H. Johnson Veterans Affairs Health Care System, Charleston, 
      SC, USA.
FAU - Li, Weiguo
AU  - Li W
AD  - Department of Pathology & Laboratory Medicine, Medical University of South 
      Carolina, USA; Ralph H. Johnson Veterans Affairs Health Care System, Charleston, 
      SC, USA.
FAU - Ergul, Adviye
AU  - Ergul A
AD  - Department of Pathology & Laboratory Medicine, Medical University of South 
      Carolina, USA; Ralph H. Johnson Veterans Affairs Health Care System, Charleston, 
      SC, USA. Electronic address: ergul@musc.edu.
LA  - eng
GR  - R01 NS104573/NS/NINDS NIH HHS/United States
GR  - IK6 BX004471/BX/BLRD VA/United States
GR  - I01 BX000347/BX/BLRD VA/United States
GR  - UL1 TR001450/TR/NCATS NIH HHS/United States
GR  - RF1 NS083559/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20221209
PL  - England
TA  - Neurochem Int
JT  - Neurochemistry international
JID - 8006959
RN  - EC 3.4.24.17 (Matrix Metalloproteinase 3)
SB  - IM
MH  - Animals
MH  - Female
MH  - Male
MH  - Rats
MH  - *Diabetes Mellitus, Experimental/complications
MH  - Disease Models, Animal
MH  - *Infarction, Middle Cerebral Artery/complications
MH  - *Matrix Metalloproteinase 3/metabolism
MH  - Rats, Wistar
MH  - *Stroke/complications
MH  - *Vascular System Injuries/enzymology/etiology
MH  - *Microvessels/enzymology
MH  - Cerebrum/blood supply
PMC - PMC9839584
MID - NIHMS1857567
OTO - NOTNLM
OT  - Brain
OT  - Diabetes
OT  - Endothelial cells
OT  - MMP3
OT  - Stroke
COIS- Declaration of competing interest The authors declare that they have no known 
      competing financial interests or personal relationships that could have appeared 
      to influence the work reported in this paper.
EDAT- 2022/12/13 06:00
MHDA- 2023/01/11 06:00
PMCR- 2024/01/01
CRDT- 2022/12/12 19:25
PHST- 2022/10/12 00:00 [received]
PHST- 2022/12/01 00:00 [revised]
PHST- 2022/12/04 00:00 [accepted]
PHST- 2022/12/13 06:00 [pubmed]
PHST- 2023/01/11 06:00 [medline]
PHST- 2022/12/12 19:25 [entrez]
PHST- 2024/01/01 00:00 [pmc-release]
AID - S0197-0186(22)00187-5 [pii]
AID - 10.1016/j.neuint.2022.105462 [doi]
PST - ppublish
SO  - Neurochem Int. 2023 Jan;162:105462. doi: 10.1016/j.neuint.2022.105462. Epub 2022 
      Dec 9.