PMID- 23571276
OWN - NLM
STAT- MEDLINE
DCOM- 20130906
LR  - 20211021
IS  - 1559-7016 (Electronic)
IS  - 0271-678X (Print)
IS  - 0271-678X (Linking)
VI  - 33
IP  - 7
DP  - 2013 Jul
TI  - Early inhibition of MMP activity in ischemic rat brain promotes expression of 
      tight junction proteins and angiogenesis during recovery.
PG  - 1104-14
LID - 10.1038/jcbfm.2013.56 [doi]
AB  - In cerebral ischemia, matrix metalloproteinases (MMPs) have a dual role by 
      acutely disrupting tight junction proteins (TJPs) in the blood-brain barrier 
      (BBB) and chronically promoting angiogenesis. Since TJP remodeling of the 
      neurovascular unit (NVU) is important in recovery and early inhibition of MMPs is 
      neuroprotective, we hypothesized that short-term MMP inhibition would reduce 
      infarct size and promote angiogenesis after ischemia. Adult spontaneously 
      hypertensive rats had a transient middle cerebral artery occlusion with 
      reperfusion. At the onset of ischemia, they received a single dose of the MMP 
      inhibitor, GM6001. They were studied at multiple times up to 4 weeks with 
      immunohistochemistry, biochemistry, and magnetic resonance imaging (MRI). We 
      observed newly formed vessels in peri-infarct regions at 3 weeks after 
      reperfusion. Dynamic contrast-enhanced MRI showed BBB opening in new vessels. 
      Along with the new vessels, pericytes expressed zonula occludens-1 (ZO-1) and 
      MMP-3, astrocytes expressed ZO-1, occludin, and MMP-2, while endothelial cells 
      expressed claudin-5. The GM6001, which reduced tissue loss at 3 to 4 weeks, 
      significantly increased new vessel formation with expression of TJPs and MMPs. 
      Our results show that pericytes and astrocytes act spatiotemporally, contributing 
      to extraendothelial TJP formation, and that MMPs are involved in BBB restoration 
      during recovery. Early MMP inhibition benefits neurovascular remodeling after 
      stroke.
FAU - Yang, Yi
AU  - Yang Y
AD  - Department of Neurology, University of New Mexico Health Sciences Center, 
      Albuquerque, New Mexico, USA.
FAU - Thompson, Jeffrey F
AU  - Thompson JF
FAU - Taheri, Saeid
AU  - Taheri S
FAU - Salayandia, Victor M
AU  - Salayandia VM
FAU - McAvoy, Thera A
AU  - McAvoy TA
FAU - Hill, Jeff W
AU  - Hill JW
FAU - Yang, Yirong
AU  - Yang Y
FAU - Estrada, Eduardo Y
AU  - Estrada EY
FAU - Rosenberg, Gary A
AU  - Rosenberg GA
LA  - eng
GR  - R01 NS045847/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20130410
PL  - United States
TA  - J Cereb Blood Flow Metab
JT  - Journal of cerebral blood flow and metabolism : official journal of the 
      International Society of Cerebral Blood Flow and Metabolism
JID - 8112566
RN  - 0 (Dipeptides)
RN  - 0 (Matrix Metalloproteinase Inhibitors)
RN  - 0 (N-(2(R)-2-(hydroxamidocarbonylmethyl)-4-methylpentanoyl)-L-tryptophan 
      methylamide)
RN  - 0 (Tight Junction Proteins)
RN  - EC 3.4.24.- (Matrix Metalloproteinases)
SB  - IM
MH  - Animals
MH  - Blood-Brain Barrier/drug effects/embryology/physiopathology
MH  - Blotting, Western
MH  - Brain Ischemia/*drug therapy/enzymology/pathology/physiopathology
MH  - Cell Death/drug effects
MH  - DNA Fragmentation/drug effects
MH  - Dipeptides/administration & dosage/*therapeutic use
MH  - In Situ Nick-End Labeling
MH  - Magnetic Resonance Imaging
MH  - Male
MH  - Matrix Metalloproteinase Inhibitors/administration & dosage/*therapeutic use
MH  - Matrix Metalloproteinases/*metabolism
MH  - Neovascularization, Physiologic/*drug effects
MH  - Rats
MH  - Rats, Inbred SHR
MH  - Tight Junction Proteins/*biosynthesis
PMC - PMC3705440
EDAT- 2013/04/11 06:00
MHDA- 2013/09/07 06:00
PMCR- 2014/07/01
CRDT- 2013/04/11 06:00
PHST- 2012/12/03 00:00 [received]
PHST- 2013/03/07 00:00 [revised]
PHST- 2013/03/14 00:00 [accepted]
PHST- 2013/04/11 06:00 [entrez]
PHST- 2013/04/11 06:00 [pubmed]
PHST- 2013/09/07 06:00 [medline]
PHST- 2014/07/01 00:00 [pmc-release]
AID - jcbfm201356 [pii]
AID - 10.1038/jcbfm.2013.56 [doi]
PST - ppublish
SO  - J Cereb Blood Flow Metab. 2013 Jul;33(7):1104-14. doi: 10.1038/jcbfm.2013.56. 
      Epub 2013 Apr 10.