PMID- 31089963
OWN - NLM
STAT- MEDLINE
DCOM- 20200312
LR  - 20200312
IS  - 1559-1182 (Electronic)
IS  - 0893-7648 (Print)
IS  - 0893-7648 (Linking)
VI  - 56
IP  - 11
DP  - 2019 Nov
TI  - Transcriptional Response and Morphological Features of the Neurovascular Unit and 
      Associated Extracellular Matrix After Experimental Stroke in Mice.
PG  - 7631-7650
LID - 10.1007/s12035-019-1604-4 [doi]
AB  - Experimental stroke studies yielded insights into single reactions of the 
      neurovascular unit (NVU) and associated extracellular matrix (ECM). However, the 
      extent of simultaneous processes caused by ischemia and their underlying 
      transcriptional changes are still poorly understood. Strictly following the NVU 
      and ECM concept, this study explored transcriptional responses of cellular and 
      non-cellular components as well as their morphological characteristics following 
      ischemia. Mice were subjected to 4 or 24 h of unilateral middle cerebral artery 
      occlusion. In the neocortex and the striatum, cytoskeletal and glial elements as 
      well as blood-brain barrier and ECM components were analyzed using real-time PCR. 
      Western blot analyses allowed characterization of protein levels and multiple 
      immunofluorescence labeling enabled morphological assessment. Out of 37 genes 
      analyzed, the majority exhibited decreased mRNA levels in ischemic areas, while 
      changes occurred as early as 4 h after ischemia. Down-regulated mRNA levels were 
      predominantly localized in the neocortex, such as the structural elements 
      alpha-catenin 2, N-cadherin, beta-catenin 1, and betaIII-tubulin, consistently decreasing 4 
      and 24 h after ischemia. However, a few genes, e.g., claudin-5 and Pcam1, 
      exhibited increased mRNA levels after ischemia. For several components such as 
      betaIII-tubulin, N-cadherin, and beta-catenin 1, matching transcriptional and 
      immunofluorescence signals were obtained, whereas a few markers including 
      neurofilaments exhibited opposite directions. In conclusion, the variety in gene 
      regulation emphasizes the complexity of interactions within the ischemia-affected 
      NVU and ECM. These data might help to focus future research on a set of highly 
      sensitive elements, which might prospectively facilitate neuroprotective 
      strategies beyond the traditional single target perspective.
FAU - Aleithe, Susanne
AU  - Aleithe S
AD  - Department of Neurology, University of Leipzig, Liebigstr. 20, 04103, Leipzig, 
      Germany. susanne.aleithe@medizin.uni-leipzig.de.
AD  - University of Leipzig, Liebigstr. 19, 04103, Leipzig, Germany. 
      susanne.aleithe@medizin.uni-leipzig.de.
FAU - Blietz, Alexandra
AU  - Blietz A
AD  - Department of Neurology, University of Leipzig, Liebigstr. 20, 04103, Leipzig, 
      Germany.
AD  - University of Leipzig, Liebigstr. 19, 04103, Leipzig, Germany.
FAU - Mages, Bianca
AU  - Mages B
AD  - Department of Neurology, University of Leipzig, Liebigstr. 20, 04103, Leipzig, 
      Germany.
AD  - Institute of Anatomy, University of Leipzig, Liebigstr. 13, 04103, Leipzig, 
      Germany.
FAU - Hobusch, Constance
AU  - Hobusch C
AD  - Institute of Anatomy, University of Leipzig, Liebigstr. 13, 04103, Leipzig, 
      Germany.
FAU - Hartig, Wolfgang
AU  - Hartig W
AD  - University of Leipzig, Liebigstr. 19, 04103, Leipzig, Germany.
FAU - Michalski, Dominik
AU  - Michalski D
AUID- ORCID: 0000-0002-0206-5380
AD  - Department of Neurology, University of Leipzig, Liebigstr. 20, 04103, Leipzig, 
      Germany. dominik.michalski@medizin.uni-leipzig.de.
LA  - eng
GR  - 100270131/Europaischer Sozialfonds/
PT  - Journal Article
DEP - 20190514
PL  - United States
TA  - Mol Neurobiol
JT  - Molecular neurobiology
JID - 8900963
RN  - 0 (Biomarkers)
RN  - 0 (Neurofilament Proteins)
RN  - 0 (RNA, Messenger)
RN  - 0 (neurofilament protein L)
SB  - IM
MH  - Animals
MH  - Biomarkers/metabolism
MH  - Blood-Brain Barrier/metabolism
MH  - Brain/*blood supply/*metabolism
MH  - Brain Ischemia/genetics/pathology
MH  - Extracellular Matrix/*metabolism
MH  - Gene Expression Regulation
MH  - Male
MH  - Mice, Inbred C57BL
MH  - Neocortex/pathology
MH  - Neurofilament Proteins/metabolism
MH  - Neuroglia/metabolism
MH  - RNA, Messenger/genetics/metabolism
MH  - Stroke/*genetics/*pathology
MH  - *Transcription, Genetic
PMC - PMC6815284
OTO - NOTNLM
OT  - Extracellular matrix
OT  - Focal cerebral ischemia
OT  - Gene expression
OT  - Neurovascular unit
OT  - Stroke
COIS- The authors declare that there is no conflict of interest.
EDAT- 2019/05/16 06:00
MHDA- 2020/03/13 06:00
PMCR- 2019/05/14
CRDT- 2019/05/16 06:00
PHST- 2018/11/28 00:00 [received]
PHST- 2019/04/10 00:00 [accepted]
PHST- 2019/05/16 06:00 [pubmed]
PHST- 2020/03/13 06:00 [medline]
PHST- 2019/05/16 06:00 [entrez]
PHST- 2019/05/14 00:00 [pmc-release]
AID - 10.1007/s12035-019-1604-4 [pii]
AID - 1604 [pii]
AID - 10.1007/s12035-019-1604-4 [doi]
PST - ppublish
SO  - Mol Neurobiol. 2019 Nov;56(11):7631-7650. doi: 10.1007/s12035-019-1604-4. Epub 
      2019 May 14.