QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: jpet.104.067090v1 310/3/890    most recent Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Banfi, C. Articles by Mussoni, L. Search for Related Content PubMed PubMed Citation Articles by Banfi, C. Articles by Mussoni, L.

INFLAMMATION AND IMMUNOPHARMACOLOGY

Pentoxifylline Prevents Spontaneous Brain Ischemia in Stroke-Prone Rats

Department of Pharmacological Sciences, Centre for Excellence on Neurodegenerative Diseases, Proteomic and Protein Structure Study Group, University of Milan (C.B., L.S., P.G., S.B., E.G., U.G., E.T., L.M.); Monzino Cardiologic Center Istituto di Ricovero e Cura a Carattere Scientifico (C.B., E.T.); and Istituto Mario Negri (G.D.S., C.P.), Milano, Italy

Anti-inflammatory properties of pentoxifylline (PTX) have recently been described. Spontaneously hypertensive stroke-prone rats (SHRSP) constitute an animal model that develops an inflammatory condition that precedes the appearance of brain abnormalities. The aim of the present investigation was to assess: 1) the efficacy of PTX treatment in protecting the neural system in SHRSP, and 2) how its anti-inflammatory properties might be involved in this effect. Male SHRSP fed with a permissive diet received no drug or PTX (100 or 200 mg/kg/day). Brain abnormalities detected by magnetic resonance imaging developed spontaneously in control rats after 42 ± 3 days, whereas in rats treated with 100 mg/kg/day PTX, abnormalities developed in only 80% of the animals and only after 70 to 80 days. Treatment with a higher dose of PTX (200 mg/kg/day) completely protected the brain from abnormal development. The drug treatment prevented the accumulation of macrophages or CD4⁺ positive cells, the activation of glia in brain tissues, and the appearance of inflammatory proteins and thiobarbituric acid-reactive substances in body fluids. PTX treatment did induce a greater increase of serum tumor necrosis factor- (TNF-), but not of interleukin (IL)-1 and IL-6 induced by in vivo administration of lipopolysaccharide (LPS), which suggests a protective role for TNF-. PTX also exerted protective effects when it was administered after the first occurrence of proteinuria (>40 mg/day). These data indicate that PTX treatment dose-dependently prevents the occurrence of spontaneous brain damage by reducing inflammatory events. We also hypothesize that the increase of TNF- by PTX treatment represents a protective mechanism in SHRSP.

Address correspondence to: Luciana Mussoni, Department of Pharmacological Sciences, University of Milan, Via Balzaretti 9, 20133 Milan, Italy. E-mail: luciana.mussoni{at}unimi.it

This article has been cited by other articles:

				X. Deng, J. P. Luyendyk, P. E. Ganey, and R. A. Roth Inflammatory Stress and Idiosyncratic Hepatotoxicity: Hints from Animal Models Pharmacol. Rev., September 1, 2009; 61(3): 262 - 282. [Abstract] [Full Text] [PDF]

				F. F. Tukov, J. P. Luyendyk, P. E. Ganey, and R. A. Roth The Role of Tumor Necrosis Factor Alpha in Lipopolysaccharide/Ranitidine-Induced Inflammatory Liver Injury Toxicol. Sci., November 1, 2007; 100(1): 267 - 280. [Abstract] [Full Text] [PDF]