PMID- 23696861
OWN - NLM
STAT- MEDLINE
DCOM- 20131223
LR  - 20211021
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 8
IP  - 5
DP  - 2013
TI  - Opening of the blood-brain barrier before cerebral pathology in mild 
      hyperhomocysteinemia.
PG  - e63951
LID - 10.1371/journal.pone.0063951 [doi]
LID - e63951
AB  - Hyperhomocysteinemia (HHcy) is a risk factor for cognitive impairment. The 
      purpose of this study was to determine the temporal pattern of cerebral pathology 
      in a mouse model of mild HHcy, because understanding this time course provides 
      the basis for understanding the mechanisms involved. C57Bl/6 mice with 
      heterozygous deletion cystathionine beta-synthase (cbs (+/-); Het) were used as a 
      model of mild HHcy along with their wild-type littermates (cbs (+/+); WT). Mice 
      were 'young' (5.3+/-0.2 months of age) and 'old' (16.6+/-0.9 months of age). 
      Blood-brain barrier (BBB) permeability was quantified from Evans blue and sodium 
      fluorescein extravasation. Microvascular architecture was assessed by z-stack 
      confocal microscopy. Leukoaraiosis was measured from Luxol fast blue stained 
      slides of paraffin brain sections. Inflammation was quantified using standard 
      antibody-based immunohistochemical techniques. Cognitive function was assessed 
      using the Morris water maze. BBB permeability was significantly greater in Het 
      vs. WT mice at all ages (p<0.05). There were no differences in microvascular 
      architecture among the groups. Compared with all other groups, old Het mice had 
      significantly greater leukoaraiosis, inflammation in the fornix, and cognitive 
      impairment (p<0.05). In mild HHcy, increased permeability of the BBB precedes the 
      onset of cerebral pathology. This new paradigm may play a role in the progression 
      of disease in HHcy.
FAU - Rhodehouse, Bryce C
AU  - Rhodehouse BC
AD  - Department of Biological Sciences, Idaho State University, Pocatello, Idaho, 
      United States of America.
FAU - Mayo, Jamie N
AU  - Mayo JN
FAU - Beard, Richard S Jr
AU  - Beard RS Jr
FAU - Chen, Cheng-Hung
AU  - Chen CH
FAU - Bearden, Shawn E
AU  - Bearden SE
LA  - eng
GR  - P20 RR016454/RR/NCRR NIH HHS/United States
GR  - R15 HL106548/HL/NHLBI NIH HHS/United States
GR  - P20 RR-016454/RR/NCRR NIH HHS/United States
GR  - HL106548/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20130516
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 45PG892GO1 (Evans Blue)
RN  - EC 4.2.1.22 (Cystathionine beta-Synthase)
SB  - IM
MH  - Animals
MH  - Blood-Brain Barrier/*pathology/physiopathology
MH  - Brain/*pathology/physiopathology
MH  - Cystathionine beta-Synthase/genetics/metabolism
MH  - Disease Models, Animal
MH  - Evans Blue/chemistry
MH  - Hyperhomocysteinemia/pathology/*physiopathology
MH  - Leukoaraiosis/pathology
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Microscopy, Confocal
PMC - PMC3655957
COIS- Competing Interests: Author Shawn Bearden is an Academic Editor for PLOS ONE. 
      This does not alter the authors' adherence to all the PLOS ONE policies on 
      sharing data and materials.
EDAT- 2013/05/23 06:00
MHDA- 2013/12/24 06:00
PMCR- 2013/05/16
CRDT- 2013/05/23 06:00
PHST- 2013/01/13 00:00 [received]
PHST- 2013/04/08 00:00 [accepted]
PHST- 2013/05/23 06:00 [entrez]
PHST- 2013/05/23 06:00 [pubmed]
PHST- 2013/12/24 06:00 [medline]
PHST- 2013/05/16 00:00 [pmc-release]
AID - PONE-D-13-02008 [pii]
AID - 10.1371/journal.pone.0063951 [doi]
PST - epublish
SO  - PLoS One. 2013 May 16;8(5):e63951. doi: 10.1371/journal.pone.0063951. Print 2013.