PMID- 18560439
OWN - NLM
STAT- MEDLINE
DCOM- 20081017
LR  - 20080924
IS  - 1559-7016 (Electronic)
IS  - 0271-678X (Linking)
VI  - 28
IP  - 10
DP  - 2008 Oct
TI  - Tissue inhibitor of metalloproteinases protect blood-brain barrier disruption in 
      focal cerebral ischemia.
PG  - 1674-85
LID - 10.1038/jcbfm.2008.59 [doi]
AB  - Enhanced matrix metalloproteinases (MMPs) can cause vasogenic edema and 
      hemorrhagic transformation after cerebral ischemia, and affect the extent of 
      ischemic injury. We hypothesized that the endogenous MMP inhibitors, tissue 
      inhibitor of MMPs (TIMPs), were essential to protect against blood-brain barrier 
      (BBB) disruption after ischemia by regulating the activities of MMPs. We 
      confirmed the transition of MMP-2 and MMP-9, and the TIMPs family after 30 mins 
      of middle cerebral artery occlusion, and elucidated the function of TIMP-1 and 
      TIMP-2 in focal ischemia, using TIMP-1(-/-) and TIMP-2(-/-) mice. TIMP-1 mRNA 
      expression was gradually increased until 24 h after reperfusion. In TIMP-1(-/-) 
      mice, MMP-9 protein expression and gelatinolytic activity were significantly more 
      augmented after cerebral ischemia than those in WT mice, and were accompanied by 
      exacerbated BBB disruption, neuronal apoptosis, and ischemic injury. In contrast, 
      TIMP-2 gene deletion mice exhibited no significant difference in MMP expressions 
      and the degree of ischemic injury despite an increased Evans blue leakage. These 
      results suggest that TIMP-1 inhibits MMP-9 activity and can play a 
      neuroprotective role in cerebral ischemia.
FAU - Fujimoto, Motoaki
AU  - Fujimoto M
AD  - Department of Neurosurgery, Graduate School of Medicine, Kyoto University, Kyoto, 
      Japan.
FAU - Takagi, Yasushi
AU  - Takagi Y
FAU - Aoki, Tomohiro
AU  - Aoki T
FAU - Hayase, Makoto
AU  - Hayase M
FAU - Marumo, Takeshi
AU  - Marumo T
FAU - Gomi, Masanori
AU  - Gomi M
FAU - Nishimura, Masaki
AU  - Nishimura M
FAU - Kataoka, Hiroharu
AU  - Kataoka H
FAU - Hashimoto, Nobuo
AU  - Hashimoto N
FAU - Nozaki, Kazuhiko
AU  - Nozaki K
LA  - eng
PT  - Journal Article
DEP - 20080618
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 (RNA, Messenger)
RN  - 0 (Tissue Inhibitor of Metalloproteinase-1)
RN  - 127497-59-0 (Tissue Inhibitor of Metalloproteinase-2)
RN  - EC 3.4.22.- (Caspase 3)
RN  - EC 3.4.24.24 (Matrix Metalloproteinase 2)
RN  - EC 3.4.24.35 (Matrix Metalloproteinase 9)
SB  - IM
MH  - Animals
MH  - Apoptosis/physiology
MH  - Blood-Brain Barrier/*physiology
MH  - Brain/*blood supply/metabolism/pathology
MH  - Brain Ischemia/metabolism/pathology/*physiopathology
MH  - Caspase 3/metabolism
MH  - Male
MH  - Matrix Metalloproteinase 2/metabolism
MH  - Matrix Metalloproteinase 9/metabolism
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Neurons/pathology/physiology
MH  - RNA, Messenger/metabolism
MH  - Tight Junctions/metabolism
MH  - Tissue Inhibitor of Metalloproteinase-1/*genetics/metabolism
MH  - Tissue Inhibitor of Metalloproteinase-2/*genetics/metabolism
EDAT- 2008/06/19 09:00
MHDA- 2008/10/18 09:00
CRDT- 2008/06/19 09:00
PHST- 2008/06/19 09:00 [pubmed]
PHST- 2008/10/18 09:00 [medline]
PHST- 2008/06/19 09:00 [entrez]
AID - jcbfm200859 [pii]
AID - 10.1038/jcbfm.2008.59 [doi]
PST - ppublish
SO  - J Cereb Blood Flow Metab. 2008 Oct;28(10):1674-85. doi: 10.1038/jcbfm.2008.59. 
      Epub 2008 Jun 18.