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

Background and Purpose-A high degree of proteinuria has been reported in st roke-prone spontaneously hypertensive rats (SHRSP). We studied the effect o f salt loading on the detailed protein pattern of serum and urine in 3 rat strains: Wistar-Kyoto, spontaneously hypertensive rats, and SHRSP, an inbre d animal model for a complex form of cerebrovascular disorder resembling th e 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-dimen sional electrophoretic analysis. Brain alterations were monitored by MRI an d histology. Results-Several proteins were excreted in urine after weeks of treatment an d in advance of stroke: transferrin, hemopexin, albumin, alpha (2)-HS-glyco protein, kallikrein-binding protein, alpha (1)-antitrypsin, Gc-globulin, an d transthyretin. Markers of an inflammatory response, including very high l evels of thiostatin, were detected in the serum of SHRSP at least 4 weeks b efore a stroke occurred. Conclusions-In SHRSP subjected to salt loading, an atypical inflammatory co ndition and widespread alterations of vascular permeability developed befor e the appearance of anomalous features in the brain detected by MRI. Urinar y concentrations of each of the excreted serum proteins correlated positive ly with time before stroke occurred.