PMID- 28860977
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20200929
IS  - 1662-5145 (Print)
IS  - 1662-5145 (Electronic)
IS  - 1662-5145 (Linking)
VI  - 11
DP  - 2017
TI  - Damaged Neocortical Perineuronal Nets Due to Experimental Focal Cerebral Ischemia 
      in Mice, Rats and Sheep.
PG  - 15
LID - 10.3389/fnint.2017.00015 [doi]
LID - 15
AB  - As part of the extracellular matrix (ECM), perineuronal nets (PNs) are 
      polyanionic, chondroitin sulfate proteoglycan (CSPG)-rich coatings of certain 
      neurons, known to be affected in various neural diseases. Although these 
      structures are considered as important parts of the neurovascular unit (NVU), 
      their role during evolution of acute ischemic stroke and subsequent tissue damage 
      is poorly understood and only a few preclinical studies analyzed PNs after acute 
      ischemic stroke. By employing three models of experimental focal cerebral 
      ischemia, this study was focused on histopathological alterations of PNs and 
      concomitant vascular, glial and neuronal changes according to the NVU concept. We 
      analyzed brain tissues obtained 1 day after ischemia onset from: (a) mice after 
      filament-based permanent middle cerebral artery occlusion (pMCAO); (b) rats 
      subjected to thromboembolic MACO; and (c) sheep at 14 days after 
      electrosurgically induced focal cerebral ischemia. Multiple fluorescence labeling 
      was applied to explore simultaneous alterations of NVU and ECM. Serial mouse 
      sections labeled with the net marker Wisteria floribunda agglutinin (WFA) 
      displayed largely decomposed and nearly erased PNs in infarcted neocortical areas 
      that were demarcated by up-regulated immunoreactivity for vascular collagen IV 
      (Coll IV). Subsequent semi-quantitative analyses in mice confirmed significantly 
      decreased WFA-staining along the ischemic border zone and a relative decrease in 
      the directly ischemia-affected neocortex. Triple fluorescence labeling throughout 
      the three animal models revealed up-regulated Coll IV and decomposed PNs 
      accompanied by activated astroglia and altered immunoreactivity for parvalbumin, 
      a calcium-binding protein in fast-firing GABAergic neurons which are 
      predominantly surrounded by neocortical PNs. Furthermore, ischemic neocortical 
      areas in rodents simultaneously displayed less intense staining of WFA, aggrecan, 
      the net components neurocan, versican and the cartilage link protein (CRTL) as 
      well as markers in net-bearing neurons such as the potassium channel subunit 
      Kv3.1b and neuronal nuclei (NeuN). In summary, theconsistent observations based 
      on three different stroke models confirmed that PNs are highly sensitive 
      constituents of the NVU along with impaired associated GABAergic neurons. These 
      results suggest that PNs could be promising targets of future stroke treatment, 
      and further studies should address their reorganization and plasticity in both 
      stabilizing the acute stroke as well as supportive effects during the chronic 
      phase of stroke.
FAU - Hartig, Wolfgang
AU  - Hartig W
AD  - Department of Pathophysiology of Neuroglia, Paul Flechsig Institute for Brain 
      Research, University of LeipzigLeipzig, Germany.
FAU - Mages, Bianca
AU  - Mages B
AD  - Department of Pathophysiology of Neuroglia, Paul Flechsig Institute for Brain 
      Research, University of LeipzigLeipzig, Germany.
AD  - Department of Neurology, University of LeipzigLeipzig, Germany.
FAU - Aleithe, Susanne
AU  - Aleithe S
AD  - Department of Pathophysiology of Neuroglia, Paul Flechsig Institute for Brain 
      Research, University of LeipzigLeipzig, Germany.
AD  - Department of Neurology, University of LeipzigLeipzig, Germany.
FAU - Nitzsche, Bjorn
AU  - Nitzsche B
AD  - Department of Nuclear Medicine, University of LeipzigLeipzig, Germany.
AD  - Faculty of Veterinary Medicine, Institute of Anatomy, Histology and Embryology, 
      University of LeipzigLeipzig, Germany.
FAU - Altmann, Stephan
AU  - Altmann S
AD  - Department of Pathophysiology of Neuroglia, Paul Flechsig Institute for Brain 
      Research, University of LeipzigLeipzig, Germany.
AD  - Department of Neurology, University of LeipzigLeipzig, Germany.
FAU - Barthel, Henryk
AU  - Barthel H
AD  - Department of Nuclear Medicine, University of LeipzigLeipzig, Germany.
FAU - Krueger, Martin
AU  - Krueger M
AD  - Institute of Anatomy, University of LeipzigLeipzig, Germany.
FAU - Michalski, Dominik
AU  - Michalski D
AD  - Department of Neurology, University of LeipzigLeipzig, Germany.
LA  - eng
PT  - Journal Article
DEP - 20170815
PL  - Switzerland
TA  - Front Integr Neurosci
JT  - Frontiers in integrative neuroscience
JID - 101477950
PMC - PMC5559442
OTO - NOTNLM
OT  - WFA
OT  - aggrecan
OT  - animal model
OT  - cerebral ischemia
OT  - extracellular matrix
OT  - neurovascular unit
OT  - stroke
EDAT- 2017/09/02 06:00
MHDA- 2017/09/02 06:01
PMCR- 2017/01/01
CRDT- 2017/09/02 06:00
PHST- 2017/05/16 00:00 [received]
PHST- 2017/07/10 00:00 [accepted]
PHST- 2017/09/02 06:00 [entrez]
PHST- 2017/09/02 06:00 [pubmed]
PHST- 2017/09/02 06:01 [medline]
PHST- 2017/01/01 00:00 [pmc-release]
AID - 10.3389/fnint.2017.00015 [doi]
PST - epublish
SO  - Front Integr Neurosci. 2017 Aug 15;11:15. doi: 10.3389/fnint.2017.00015. 
      eCollection 2017.