The association between hypertensive arteriopathy and cerebral amyloid angiopathy in spontaneously hypertensive stroke-prone rats

Brain Pathol. 2018 Nov;28(6):844-859. doi: 10.1111/bpa.12629. Epub 2018 Oct 10.

Abstract

We aimed to test the hypothesis that in spontaneously hypertensive stroke-prone rats (SHRSP), non-amyloid cerebral small vessel disease/hypertensive arteriopathy (HA) results in vessel wall injury that may promote cerebral amyloid angiopathy (CAA). Our study comprised 21 male SHRSP (age 17-44 weeks) and 10 age- and sex-matched Wistar control rats, that underwent two-photon (2PM) imaging of the arterioles in the parietal cortex using Methoxy-X04, Dextran and cerebral blood flow (CBF) measurements. Our data suggest that HA in SHRSP progresses in a temporal and age-dependent manner, starting from small vessel wall damage (stage 1A), proceeding to CBF reduction (stage 1B), non-occlusive (stage 2), and finally, occlusive thrombi (stage 3). Wistar animals also demonstrated small vessel wall damage, but were free of any of the later HA stages. Nearly half of all SHRSP additionally displayed vascular Methoxy-X04 positivity indicative of cortical CAA. Vascular β-amyloid deposits were found in small vessels characterized by thrombotic occlusions (stage 2 or 3). Post-mortem analysis of the rat brains confirmed the findings derived from intravital 2PM microscopy. Our data thus overall suggest that advanced HA may play a role in CAA development with the two small vessel disease entities might be related to the same pathological spectrum of the aging brain.

Keywords: cerebral amyloid angiopathy; cerebral small vessel disease; hypertensive arteriopathy; intravital imaging; spontaneously hypertensive stroke-prone rat.

MeSH terms

  • Aging
  • Amyloid beta-Peptides / metabolism
  • Animals
  • Arterioles / diagnostic imaging
  • Arterioles / pathology
  • Autopsy
  • Brain / pathology
  • Cerebral Amyloid Angiopathy / diagnostic imaging
  • Cerebral Amyloid Angiopathy / etiology*
  • Cerebral Amyloid Angiopathy / pathology*
  • Cerebral Small Vessel Diseases / complications*
  • Cerebral Small Vessel Diseases / diagnostic imaging
  • Cerebral Small Vessel Diseases / etiology
  • Cerebral Small Vessel Diseases / pathology*
  • Cerebrovascular Circulation / physiology
  • Disease Models, Animal
  • Female
  • Hypertension / complications
  • Hypertension / pathology*
  • Intravital Microscopy
  • Male
  • Rats
  • Rats, Inbred SHR
  • Rats, Wistar

Substances

  • Amyloid beta-Peptides