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(Stroke. 2001;32:753.)
© 2001 American Heart Association, Inc.

Original Contributions

Acute-Phase Proteins Before Cerebral Ischemia in Stroke-Prone Rats

Identification by Proteomics

Luigi Sironi, PhD; Elena Tremoli, PhD; Ingrid Miller, MS; Uliano Guerrini, PhD; Anna Maria Calvio, MS; Ivano Eberini, MS; Manfred Gemeiner, PhD; Maria Asdente, PhD; Rodolfo Paoletti, MD Elisabetta Gianazza, PhD

From the Dipartimento di Scienze Farmacologiche, Facoltà di Farmacia, Università degli Studi, Milan, Italy (L.S., E.T., U.G., A.M.C., I.E., M.A., R.P., E.G.), and Institut für Medizinische Chemie, Veterinärmedizinische Universität, Vienna, Austria (I.M., M.G.).

Correspondence to Elisabetta Gianazza, PhD, Dipartimento di Scienze Farmacologiche, Facoltà di Farmacia, Università degli Studi di Milano, via Balzaretti 9, I-20133 Milan, Italy. E-mail Elisabetta.Gianazza{at}unimi.it

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, ₂-HS-glycoprotein, kallikrein-binding protein, 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.

Key Words: animal models • inflammation • nuclear magnetic resonance • proteome • stroke • rats

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