title: NAC changes the course of cerebral small vessel disease in SHRSP and reveals new insights for the meaning of stases - a randomized controlled study.
abstract: BACKGROUND
  N-Acetylcystein (NAC) reduces the reperfusion injury and infarct size in experimental macroangiopathic stroke. Here we now investigate the impact of NAC on the development of the histopathology of microangiopathic cerebrovascular disease including initial intravasal erythrocyte accumulations, blood-brain-barrier (BBB)-disturbances, microbleeds and infarcts.
  
  
  METHODS
  Spontaneously Hypertensive Stroke-Prone Rats (SHRSP) were treated with NAC (12 mg/kg body weight, daily oral application for three to 30 weeks) and compared to untreated SHRSP. In all rats the number of microbleeds, thromboses, infarcts and stases were quantified by HE-staining. Exemplary brains were stained against von Willebrand factor (vWF), IgG, Glutathione and GFAP.
  
  
  RESULTS
  NAC animals exhibited significant more microbleeds, a greater number of vessels with BBB-disturbances, but also an elevation of Glutathione-levels in astrocytes surrounding small vessels. NAC-treatment reduced the numbers of thromboses, infarcts and arteriolar stases.
  
  
  CONCLUSIONS
  NAC reduces the frequency of thromboses and infarcts to the expense of an increase of small microbleeds in a rat model of microangiopathic cerebrovascular disease. We suppose that NAC acts via an at least partial inactivation of vWF resulting in an insufficient sealing of initial endothelial injury leading to more small microbleeds. By elevating Glutathione-levels NAC most likely exerts a radical scavenger function and protects small vessels against extended ruptures and subsequent infarcts. Finally, it reveals that stases are mainly caused by endothelial injuries and restricted thromboses.
authors.affiliation: Department of Neurology, Otto-von-Guericke-University, Leipziger Strasse 44, Magdeburg, 39120, Germany.
authors.forename: Celine Zoe
authors.initials: CZ
authors.lastname: Bueche
authors.affiliation: Department of Neurology, Otto-von-Guericke-University, Leipziger Strasse 44, Magdeburg, 39120, Germany.
authors.forename: Cornelia
authors.initials: C
authors.lastname: Garz
authors.affiliation: Institute of Biometry and Medical Informatics, Otto-von-Guericke-University, Leipziger Strasse 44, Magdeburg, 39120, Germany.
authors.forename: Siegfried
authors.initials: S
authors.lastname: Kropf
authors.affiliation: Department of Neurology, Otto-von-Guericke-University, Leipziger Strasse 44, Magdeburg, 39120, Germany ; German Center for Neurodegenerative Diseases (DZNE), Brenneckestrasse 6, Magdeburg, 39118, Germany.
authors.forename: Daniel
authors.initials: D
authors.lastname: Bittner
authors.affiliation: Department of Neurology, Otto-von-Guericke-University, Leipziger Strasse 44, Magdeburg, 39120, Germany.
authors.forename: Wenjie
authors.initials: W
authors.lastname: Li
authors.affiliation: Department of Neurology, Otto-von-Guericke-University, Leipziger Strasse 44, Magdeburg, 39120, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Goertler
authors.affiliation: Department of Neurology, Otto-von-Guericke-University, Leipziger Strasse 44, Magdeburg, 39120, Germany ; Leibniz Institute for Neurobiology, Brenneckestrasse 6, Magdeburg, 39118, Germany ; German Center for Neurodegenerative Diseases (DZNE), Brenneckestrasse 6, Magdeburg, 39118, Germany.
authors.forename: Hans-Jochen
authors.initials: HJ
authors.lastname: Heinze
authors.affiliation: Leibniz Institute for Neurobiology, Brenneckestrasse 6, Magdeburg, 39118, Germany ; German Center for Neurodegenerative Diseases (DZNE), Brenneckestrasse 6, Magdeburg, 39118, Germany.
authors.forename: Klaus
authors.initials: K
authors.lastname: Reymann
authors.affiliation: German Center for Neurodegenerative Diseases (DZNE), Brenneckestrasse 6, Magdeburg, 39118, Germany.
authors.forename: Holger
authors.initials: H
authors.lastname: Braun
authors.affiliation: Department of Neurology, Otto-von-Guericke-University, Leipziger Strasse 44, Magdeburg, 39120, Germany ; German Center for Neurodegenerative Diseases (DZNE), Brenneckestrasse 6, Magdeburg, 39118, Germany.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Schreiber
keywords: Animal model; Blood–brain barrier; Cerebral microbleed; Cerebral small vessel disease; von Willebrand factor