PMID- 28445478
OWN - NLM
STAT- MEDLINE
DCOM- 20170905
LR  - 20200204
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 12
IP  - 4
DP  - 2017
TI  - Delayed histochemical alterations within the neurovascular unit due to transient 
      focal cerebral ischemia and experimental treatment with neurotrophic factors.
PG  - e0174996
LID - 10.1371/journal.pone.0174996 [doi]
LID - e0174996
AB  - Current stroke therapy is focused on recanalizing strategies, but neuroprotective 
      co-treatments are still lacking. Modern concepts of the ischemia-affected 
      neurovascular unit (NVU) and surrounding penumbra emphasize the complexity during 
      the transition from initial damaging to regenerative processes. While early 
      treatment with neurotrophic factors was shown to result in lesion size reduction 
      and blood-brain barrier (BBB) stabilization, cellular consequences from these 
      treatments are poorly understood. This study explored delayed cellular responses 
      not only to ischemic stroke, but also to an early treatment with neurotrophic 
      factors. Rats underwent 60 minutes of focal cerebral ischemia. Fluorescence 
      labeling was applied to sections from brains perfused 7 days after ischemia. 
      Analyses focused on NVU constituents including the vasculature, astrocytes and 
      microglia in the ischemic striatum, the border zone and the contralateral 
      hemisphere. In addition to histochemical signs of BBB breakdown, a strong 
      up-regulation of collagen IV and microglia activation occurred within the 
      ischemic core with simultaneous degradation of astrocytes and their endfeet. 
      Activated astroglia were mainly depicted at the border zone in terms of a glial 
      scar formation. Early treatment with pigment epithelium-derived factor (PEDF) 
      resulted in an attenuation of the usually up-regulated collagen 
      IV-immunoreactivity. However, glial activation was not influenced by treatment 
      with PEDF or the epidermal growth factor (EGF). In conclusion, these data on 
      ischemia-induced cellular reactions within the NVU might help to develop 
      treatments addressing the transition from injury towards regeneration. Thereby, 
      the integrity of the vasculature in close relation to neighboring structures like 
      astrocytes appears as a promising target.
FAU - Michalski, Dominik
AU  - Michalski D
AD  - Department of Neurology, University of Leipzig, Liebigstr. 20, Leipzig, Germany.
FAU - Pitsch, Roman
AU  - Pitsch R
AD  - Paul Flechsig Institute for Brain Research, University of Leipzig, Liebigstr. 19, 
      Leipzig, Germany.
FAU - Pillai, Deepu R
AU  - Pillai DR
AD  - Department of Neurology, University of Regensburg and Clinic for Neurological 
      Rehabilitation II, Universitatsstr. 84, Regensburg, Germany.
AD  - Institute of Neuroscience and Medicine (INM) 4, Forschungszentrum Julich GmbH, 
      Julich, Germany.
FAU - Mages, Bianca
AU  - Mages B
AD  - Department of Neurology, University of Leipzig, Liebigstr. 20, Leipzig, Germany.
AD  - Paul Flechsig Institute for Brain Research, University of Leipzig, Liebigstr. 19, 
      Leipzig, Germany.
FAU - Aleithe, Susanne
AU  - Aleithe S
AD  - Department of Neurology, University of Leipzig, Liebigstr. 20, Leipzig, Germany.
AD  - Paul Flechsig Institute for Brain Research, University of Leipzig, Liebigstr. 19, 
      Leipzig, Germany.
FAU - Grosche, Jens
AU  - Grosche J
AD  - Effigos GmbH, Am Deutschen Platz 4, Leipzig, Germany.
FAU - Martens, Henrik
AU  - Martens H
AD  - Synaptic Systems, Gottingen, Germany.
FAU - Schlachetzki, Felix
AU  - Schlachetzki F
AD  - Department of Neurology, University of Regensburg and Clinic for Neurological 
      Rehabilitation II, Universitatsstr. 84, Regensburg, Germany.
FAU - Hartig, Wolfgang
AU  - Hartig W
AD  - Paul Flechsig Institute for Brain Research, University of Leipzig, Liebigstr. 19, 
      Leipzig, Germany.
LA  - eng
PT  - Journal Article
DEP - 20170426
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Aquaporin 4)
RN  - 0 (Collagen Type IV)
RN  - 0 (Eye Proteins)
RN  - 0 (GFAP protein, rat)
RN  - 0 (Glial Fibrillary Acidic Protein)
RN  - 0 (Nerve Growth Factors)
RN  - 0 (Serpins)
RN  - 0 (Vascular Endothelial Growth Factor A)
RN  - 0 (pigment epithelium-derived factor)
RN  - 62229-50-9 (Epidermal Growth Factor)
SB  - IM
MH  - Animals
MH  - Aquaporin 4/metabolism
MH  - Astrocytes/metabolism/pathology
MH  - Blood-Brain Barrier/drug effects/metabolism
MH  - Brain/diagnostic imaging/*drug effects/metabolism/pathology
MH  - Collagen Type IV/metabolism
MH  - Disease Models, Animal
MH  - Epidermal Growth Factor/pharmacology/therapeutic use
MH  - Eye Proteins/pharmacology/therapeutic use
MH  - Glial Fibrillary Acidic Protein/metabolism
MH  - Ischemic Attack, Transient/diagnostic imaging/drug therapy/*pathology
MH  - Magnetic Resonance Imaging
MH  - Male
MH  - Microglia/metabolism/pathology
MH  - Microscopy, Fluorescence
MH  - Nerve Growth Factors/*pharmacology/therapeutic use
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Serpins/pharmacology/therapeutic use
MH  - Up-Regulation/drug effects
MH  - Vascular Endothelial Growth Factor A/metabolism
PMC - PMC5405989
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2017/04/27 06:00
MHDA- 2017/09/07 06:00
PMCR- 2017/04/26
CRDT- 2017/04/27 06:00
PHST- 2016/11/12 00:00 [received]
PHST- 2017/03/17 00:00 [accepted]
PHST- 2017/04/27 06:00 [entrez]
PHST- 2017/04/27 06:00 [pubmed]
PHST- 2017/09/07 06:00 [medline]
PHST- 2017/04/26 00:00 [pmc-release]
AID - PONE-D-16-45020 [pii]
AID - 10.1371/journal.pone.0174996 [doi]
PST - epublish
SO  - PLoS One. 2017 Apr 26;12(4):e0174996. doi: 10.1371/journal.pone.0174996. 
      eCollection 2017.