Acute-phase proteins before cerebral ischemia in stroke-prone rats: identification by proteomics

Stroke. 2001 Mar;32(3):753-60. doi: 10.1161/01.str.32.3.753.

Abstract

Background and purpose: A high degree of proteinuria has been reported in stroke-prone spontaneously hypertensive rats (SHRSP). We studied the effect of salt loading on the detailed protein pattern of serum and urine in 3 rat strains: Wistar-Kyoto, spontaneously hypertensive rats, and SHRSP, an inbred animal model for a complex form of cerebrovascular disorder resembling the human disease.

Methods: Rats were given a permissive diet and received 1% NaCl in drinking water. The protein pattern in body fluids was assessed over time by 2-dimensional electrophoretic analysis. Brain alterations were monitored by MRI and histology.

Results: Several proteins were excreted in urine after weeks of treatment and in advance of stroke: transferrin, hemopexin, albumin, alpha(2)-HS-glycoprotein, kallikrein-binding protein, alpha(1)-antitrypsin, Gc-globulin, and transthyretin. Markers of an inflammatory response, including very high levels of thiostatin, were detected in the serum of SHRSP at least 4 weeks before a stroke occurred.

Conclusions: In SHRSP subjected to salt loading, an atypical inflammatory condition and widespread alterations of vascular permeability developed before the appearance of anomalous features in the brain detected by MRI. Urinary concentrations of each of the excreted serum proteins correlated positively with time before stroke occurred.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute-Phase Proteins / metabolism*
  • Animals
  • Biomarkers / blood
  • Biomarkers / urine
  • Blood Pressure / drug effects
  • Blood Pressure / genetics
  • Blood Proteins / urine
  • Body Weight / drug effects
  • Body Weight / genetics
  • Brain / blood supply
  • Brain / pathology
  • Brain Ischemia / chemically induced
  • Brain Ischemia / diagnosis
  • Brain Ischemia / genetics
  • Brain Ischemia / metabolism*
  • Capillary Permeability / drug effects
  • Capillary Permeability / genetics
  • Disease Models, Animal
  • Electrophoresis, Gel, Two-Dimensional
  • Inflammation / blood
  • Inflammation / urine
  • Kininogens / blood
  • Magnetic Resonance Imaging
  • Male
  • Predictive Value of Tests
  • Proteome / metabolism*
  • Rats
  • Rats, Inbred SHR
  • Rats, Inbred Strains
  • Rats, Inbred WKY
  • Sodium, Dietary / pharmacology
  • Stroke / chemically induced
  • Stroke / diagnosis
  • Stroke / genetics
  • Stroke / metabolism*

Substances

  • Acute-Phase Proteins
  • Biomarkers
  • Blood Proteins
  • Kininogens
  • Proteome
  • Sodium, Dietary