PMID- 28265034
OWN - NLM
STAT- MEDLINE
DCOM- 20170703
LR  - 20230601
IS  - 1470-8736 (Electronic)
IS  - 0143-5221 (Linking)
VI  - 131
IP  - 6
DP  - 2017 Mar 1
TI  - Extracellular matrix inflammation in vascular cognitive impairment and dementia.
PG  - 425-437
LID - 10.1042/CS20160604 [doi]
AB  - Vascular cognitive impairment and dementia (VCID) include a wide spectrum of 
      chronic manifestations of vascular disease related to large vessel strokes and 
      small vessel disease (SVD). Lacunar strokes and white matter (WM) injury are 
      consequences of SVD. The main vascular risk factor for SVD is brain hypoperfusion 
      from cerebral blood vessel narrowing due to chronic hypertension. The 
      hypoperfusion leads to activation and degeneration of astrocytes with the 
      resulting fibrosis of the extracellular matrix (ECM). Elasticity is lost in 
      fibrotic cerebral vessels, reducing the response of stiffened blood vessels in 
      times of increased metabolic need. Intermittent hypoxia/ischaemia activates a 
      molecular injury cascade, producing an incomplete infarction that is most 
      damaging to the deep WM, which is a watershed region for cerebral blood flow. 
      Neuroinflammation caused by hypoxia activates microglia/macrophages to release 
      proteases and free radicals that perpetuate the damage over time to molecules in 
      the ECM and the neurovascular unit (NVU). Matrix metalloproteinases (MMPs) 
      secreted in an attempt to remodel the blood vessel wall have the undesired 
      consequences of opening the blood-brain barrier (BBB) and attacking myelinated 
      fibres. This dual effect of the MMPs causes vasogenic oedema in WM and vascular 
      demyelination, which are the hallmarks of the subcortical ischaemic vascular 
      disease (SIVD), which is the SVD form of VCID also called Binswanger's disease 
      (BD). Unravelling the complex pathophysiology of the WM injury-related 
      inflammation in the small vessel form of VCID could lead to novel therapeutic 
      strategies to reduce damage to the ECM, preventing the progressive damage to the 
      WM.
CI  - (c) 2017 The Author(s). published by Portland Press Limited on behalf of the 
      Biochemical Society.
FAU - Rosenberg, Gary A
AU  - Rosenberg GA
AD  - Department of Neurology, UNM Memory and Aging Center, University of New Mexico, 
      Albuquerque NM 87131-0001, U.S.A. grosenberg@salud.unm.edu.
LA  - eng
GR  - R01 NS052305/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Review
PL  - England
TA  - Clin Sci (Lond)
JT  - Clinical science (London, England : 1979)
JID - 7905731
RN  - 0 (Matrix Metalloproteinase Inhibitors)
RN  - EC 3.4.24.- (Matrix Metalloproteinases)
SB  - IM
MH  - Animals
MH  - Cognition Disorders/enzymology/*etiology/physiopathology
MH  - Dementia, Vascular/enzymology/*etiology/physiopathology
MH  - Disease Models, Animal
MH  - Extracellular Matrix/enzymology/*pathology/physiology
MH  - Humans
MH  - Hypertension/complications
MH  - Inflammation/*complications/drug therapy/enzymology/pathology/physiopathology
MH  - Matrix Metalloproteinase Inhibitors/therapeutic use
MH  - Matrix Metalloproteinases/metabolism
OTO - NOTNLM
OT  - Binswanger's disease
OT  - demyelination
OT  - extracellular matrix
OT  - gliosis
OT  - matrix metalloproteinases
OT  - neuroinflammation
OT  - vascular cognitive impairment
EDAT- 2017/03/08 06:00
MHDA- 2017/07/04 06:00
CRDT- 2017/03/08 06:00
PHST- 2016/11/03 00:00 [received]
PHST- 2016/12/15 00:00 [revised]
PHST- 2016/12/19 00:00 [accepted]
PHST- 2017/03/08 06:00 [entrez]
PHST- 2017/03/08 06:00 [pubmed]
PHST- 2017/07/04 06:00 [medline]
AID - CS20160604 [pii]
AID - 10.1042/CS20160604 [doi]
PST - ppublish
SO  - Clin Sci (Lond). 2017 Mar 1;131(6):425-437. doi: 10.1042/CS20160604.