PMID- 22387049
OWN - NLM
STAT- MEDLINE
DCOM- 20130215
LR  - 20120827
IS  - 1872-9452 (Electronic)
IS  - 0098-2997 (Linking)
VI  - 33
IP  - 5-6
DP  - 2012 Oct-Dec
TI  - The disturbed blood-brain barrier in human glioblastoma.
PG  - 579-89
LID - 10.1016/j.mam.2012.02.003 [doi]
AB  - The aim of this article is to describe alterations of the blood-brain barrier 
      (BBB) in gliomas. The main clinical problem of human gliomas is the edematous 
      swelling and the dramatic increase of intracerebral pressure, also compromising 
      healthy areas of the brain. According to our concept, one of the main reasons on 
      the cellular level for these clinical problems is the loss or reduction of 
      astroglial polarity. Astroglial polarity means the specific accumulation of 
      potassium and water channels in the superficial and perivascular astroglial 
      endfeet membranes. The most important water channel in the CNS is the astroglial 
      water channel protein aquaporin-4 (AQP4) which is arranged in a morphologically 
      spectacular way, the so-called orthogonal arrays of particles (OAPs) to be 
      observed in freeze-fracture replicas. In brain tumors, but also under conditions 
      of trauma or inflammation, these OAPs are redistributed to membrane domains apart 
      from endfeet areas. Probably, this dislocation might be due to the degradation of 
      the proteoglycan agrin by the matrix metalloproteinase 3 (MMP3). Agrin binds to 
      the dystrophin-dystroglycan-complex (DDC), which in turn is connected to AQP4. As 
      a consequence, agrin loss may lead to a redistribution of AQP4 and a compromised 
      directionality of water transport out of the cell, finally to cytotoxic edema. 
      This in turn is hypothesized to lead to a breakdown of the BBB characterized by 
      disturbed tight junctions, and thus to the development of vasogenic edema. 
      However, the mechanism how the loss of polarity is related to the disturbance of 
      microvascular tight junctions is completely unknown so far.
CI  - Copyright (c) 2012 Elsevier Ltd. All rights reserved.
FAU - Wolburg, Hartwig
AU  - Wolburg H
AD  - Department of General Pathology and Pathological Anatomy, Institute of Pathology 
      and Neuropathology, University of Tubingen, Tubingen, Germany. 
      hartwig.wolburg@med.uni-tuebingen.de
FAU - Noell, Susan
AU  - Noell S
FAU - Fallier-Becker, Petra
AU  - Fallier-Becker P
FAU - Mack, Andreas F
AU  - Mack AF
FAU - Wolburg-Buchholz, Karen
AU  - Wolburg-Buchholz K
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
DEP - 20120223
PL  - England
TA  - Mol Aspects Med
JT  - Molecular aspects of medicine
JID - 7603128
RN  - 0 (AQP4 protein, human)
RN  - 0 (Agrin)
RN  - 0 (Aquaporin 4)
RN  - 0 (Dystrophin)
RN  - 146888-27-9 (Dystroglycans)
RN  - EC 3.4.24.17 (MMP3 protein, human)
RN  - EC 3.4.24.17 (Matrix Metalloproteinase 3)
SB  - IM
MH  - Agrin/chemistry/metabolism
MH  - Aquaporin 4/chemistry/*metabolism
MH  - Astrocytes/metabolism/pathology
MH  - Blood-Brain Barrier/*metabolism/pathology
MH  - Brain Edema/complications/*metabolism/pathology
MH  - Brain Neoplasms/complications/*metabolism/pathology
MH  - Cell Polarity
MH  - Dystroglycans/chemistry/metabolism
MH  - Dystrophin/chemistry/metabolism
MH  - Glioblastoma/complications/*metabolism/pathology
MH  - Humans
MH  - Intracranial Pressure
MH  - Matrix Metalloproteinase 3/chemistry/metabolism
MH  - Protein Conformation
MH  - Water-Electrolyte Imbalance/complications/*metabolism/pathology
EDAT- 2012/03/06 06:00
MHDA- 2013/02/16 06:00
CRDT- 2012/03/06 06:00
PHST- 2011/11/28 00:00 [received]
PHST- 2012/02/09 00:00 [revised]
PHST- 2012/02/14 00:00 [accepted]
PHST- 2012/03/06 06:00 [entrez]
PHST- 2012/03/06 06:00 [pubmed]
PHST- 2013/02/16 06:00 [medline]
AID - S0098-2997(12)00018-0 [pii]
AID - 10.1016/j.mam.2012.02.003 [doi]
PST - ppublish
SO  - Mol Aspects Med. 2012 Oct-Dec;33(5-6):579-89. doi: 10.1016/j.mam.2012.02.003. 
      Epub 2012 Feb 23.