Pentoxifylline prevents spontaneous brain ischemia in stroke-prone rats

Cristina Banfi, Luigi Sironi, Grazia De Simoni, Paolo Gelosa, Simona Barcella, Carlo Perego, Elisabetta Gianazza, Uliano Guerrini, Elena Tremoli, Luciana Mussoni

Research output: Contribution to journalArticlepeer-review

Abstract

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-α (TNF-α), but not of interleukin (IL)-1β and IL-6 induced by in vivo administration of lipopolysaccharide (LPS), which suggests a protective role for TNF-α. 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-α by PTX treatment represents a protective mechanism in SHRSP.

Original languageEnglish
Pages (from-to)890-895
Number of pages6
JournalJournal of Pharmacology and Experimental Therapeutics
Volume310
Issue number3
DOIs
Publication statusPublished - Sep 2004

ASJC Scopus subject areas

  • Pharmacology

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