title: Impact of N-Acetylcysteine on cerebral amyloid-β plaques and kidney damage in spontaneously hypertensive stroke-prone rats.
abstract: BACKGROUND
  Cerebral small vessel disease (CSVD) in spontaneously hypertensive stroke prone rats (SHRSP) is accompanied by parenchymal amyloid-β (Aβ) deposition in the brain and by hypertensive nephropathy with tubulointerstitial damage. N-acetylcysteine (NAC) promotes blood-brain barrier (BBB) breakdown in SHRSP and may thus accelerate the failure of vascular and perivascular clearance of Aβ.
  
  
  OBJECTIVE
  In this study, we test the hypothesis that treatment with NAC increases the cerebral Aβ load and improves renal damage in the SHRSP model.
  
  
  METHODS
  A total of 46 SHRSP (ages 18-44 weeks) were treated daily with NAC (12 mg/kg body weight) and 74 no-treated age-matched SHRSP served as controls. The prevalence of parenchymal Aβ load, IgG positive small vessels, and small perivascular bleeds was assessed in different brain regions. Tubulointerstitial kidney damage was assessed through a) the presence of erythrocytes in peritubular capillaries and b) tubular protein cylinders.
  
  
  RESULTS
  SHRSP treated with NAC had an age-dependent increase of BBB breakdown (assessed by the presence of IgG positive small vessels) and small perivascular bleeds, mainly in the cortex. NAC significantly increased the Aβ plaque load in the cortex while the number of parenchymal amyloid deposits in the remaining brain areas including basal ganglia, hippocampus, thalamus, and corpus callosum were unchanged. There were no significant treatment effects on tubulointerstitial kidney damage.
  
  
  CONCLUSIONS
  The impact of NAC on cerebral cortical plaque load increase may result from the vascular pathology of SHRSP that accompanies BBB breakdown, leading to the failure of amyloid clearance mechanisms. It remains to be seen whether in humans chronic NAC intake may increase amyloid load in the aging human brain and dementia.
authors.affiliation: German Center for Neurodegenerative Diseases (DZNE), Magdeburg, Germany.
authors.forename: Celine Zoe
authors.initials: CZ
authors.lastname: Bueche
authors.affiliation: Department of Neurology, Otto-von-Guericke University, Magdeburg, Germany.
authors.forename: Cornelia
authors.initials: C
authors.lastname: Garz
authors.affiliation: German Center for Neurodegenerative Diseases (DZNE), Magdeburg, Germany.
authors.forename: Luiza
authors.initials: L
authors.lastname: Stanaszek
authors.affiliation: Department of Neurology, Otto-von-Guericke University, Magdeburg, Germany.
authors.forename: Solveig
authors.initials: S
authors.lastname: Niklass
authors.affiliation: Institute of Biometry and Medical Informatics, Otto-von-Guericke University, Magdeburg, Germany.
authors.forename: Siegfried
authors.initials: S
authors.lastname: Kropf
authors.affiliation: German Center for Neurodegenerative Diseases (DZNE), Magdeburg, Germany Department of Neurology, Otto-von-Guericke University, Magdeburg, Germany.
authors.forename: Daniel
authors.initials: D
authors.lastname: Bittner
authors.affiliation: Paul-Flechsig-Institute for Brain Research, Universität Leipzig, Leipzig, Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Härtig
authors.affiliation: German Center for Neurodegenerative Diseases (DZNE), Magdeburg, Germany.
authors.forename: Klaus G
authors.initials: KG
authors.lastname: Reymann
authors.affiliation: German Center for Neurodegenerative Diseases (DZNE), Magdeburg, Germany Department of Neurology, Otto-von-Guericke University, Magdeburg, Germany.
authors.forename: Hans-Jochen
authors.initials: HJ
authors.lastname: Heinze
authors.affiliation: Institute for Life Sciences, University of Southampton, Southampton, UK.
authors.forename: Roxana O
authors.initials: RO
authors.lastname: Carare
authors.affiliation: German Center for Neurodegenerative Diseases (DZNE), Magdeburg, Germany Department of Neurology, Otto-von-Guericke University, Magdeburg, Germany.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Schreiber
mesh_terms: D000111:Acetylcysteine / Q000627:therapeutic use*; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000704:Analysis of Variance; D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000503:physiopathology; D002540:Cerebral Cortex / Q000187:drug effects* / Q000378:metabolism; D059345:Cerebral Small Vessel Diseases / Q000150:complications* / Q000209:etiology; D004195:Disease Models, Animal; D005353:Fibronectins / Q000378:metabolism; D016166:Free Radical Scavengers / Q000627:therapeutic use*; D007674:Kidney Diseases / Q000188:drug therapy / Q000209:etiology / Q000473:pathology; D037102:Lectins; D008297:Male; D058225:Plaque, Amyloid / Q000517:prevention & control; D010980:Platelet Membrane Glycoproteins / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR
chemical_list: D016229:Amyloid beta-Peptides; D005353:Fibronectins; D016166:Free Radical Scavengers; D037102:Lectins; D010980:Platelet Membrane Glycoproteins; C028254:von Willebrand factor receptor; D000111:Acetylcysteine
keywords: Amyloid-β; N-acetylcysteine rats; cerebral small vessel disease; hypertensive nephropathy; spontaneously hypertensive stroke prone rats (SHRSP)