Härtig, Wolfgang
[Author];
Mages, Bianca
[Author];
Aleithe, Susanne
[Author];
Nitzsche, Björn
[Author];
Altmann, Stephan
[Author];
Barthel, Henryk
[Author];
Krueger, Martin
[Author];
Michalski, Dominik
[Author]
Damaged Neocortical Perineuronal Nets Due to Experimental Focal Cerebral Ischemia in Mice, Rats and Sheep
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Media type:
E-Article
Title:
Damaged Neocortical Perineuronal Nets Due to Experimental Focal Cerebral Ischemia in Mice, Rats and Sheep
Contributor:
Härtig, Wolfgang
[Author];
Mages, Bianca
[Author];
Aleithe, Susanne
[Author];
Nitzsche, Björn
[Author];
Altmann, Stephan
[Author];
Barthel, Henryk
[Author];
Krueger, Martin
[Author];
Michalski, Dominik
[Author]
imprint:
Lausanne: Frontiers Research Foundation, [2023]
Published in:Frontiers in integrative neuroscience ; 11, (2017)
Description:
As part of the extracellular matrix (ECM), perineuronal nets (PNs) are polyanionic,chondroitin sulfate proteoglycan (CSPG)-rich coatings of certain neurons, known tobe affected in various neural diseases. Although these structures are consideredas important parts of the neurovascular unit (NVU), their role during evolution ofacute ischemic stroke and subsequent tissue damage is poorly understood and onlya few preclinical studies analyzed PNs after acute ischemic stroke. By employingthree models of experimental focal cerebral ischemia, this study was focused onhistopathological alterations of PNs and concomitant vascular, glial and neuronalchanges according to the NVU concept. We analyzed brain tissues obtained 1 dayafter ischemia onset from: (a) mice after filament-based permanent middle cerebralartery occlusion (pMCAO); (b) rats subjected to thromboembolic MACO; and (c) sheepat 14 days after electrosurgically induced focal cerebral ischemia. Multiple fluorescencelabeling was applied to explore simultaneous alterations of NVU and ECM. Serialmouse sections labeled with the net marker Wisteria floribunda agglutinin (WFA)displayed largely decomposed and nearly erased PNs in infarcted neocortical areas thatwere demarcated by up-regulated immunoreactivity for vascular collagen IV (Coll IV).Subsequent semi-quantitative analyses in mice confirmed significantly decreasedWFA-staining along the ischemic border zone and a relative decrease in the directlyischemia-affected neocortex. Triple fluorescence labeling throughout the three animalmodels revealed up-regulated Coll IV and decomposed PNs accompanied by activatedastroglia and altered immunoreactivity for parvalbumin, a calcium-binding protein infast-firing GABAergic neurons which are predominantly surrounded by neocorticalPNs. Furthermore, ischemic neocortical areas in rodents simultaneously displayedless intense staining of WFA, aggrecan, the net components neurocan, versican andthe cartilage link protein (CRTL) as well as markers in net-bearing neurons such asthe potassium channel subunit Kv3.1b and neuronal nuclei (NeuN). In summary, theconsistent observations based on three different stroke models confirmed that PNsare highly sensitive constituents of the NVU along with impaired associated GABAergicneurons. These results suggest that PNs could be promising targets of future stroke treatment, and further studies should address their reorganization and plasticity in bothstabilizing the acute stroke as well as supportive effects during the chronic phase ofstroke.