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 journalArticle

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

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Pentoxifylline
Brain Ischemia
Stroke
Brain
Tumor Necrosis Factor-alpha
Anti-Inflammatory Agents
Thiobarbituric Acid Reactive Substances
Body Fluids
Interleukin-1
Proteinuria
Neuroglia
Pharmaceutical Preparations
Lipopolysaccharides
Interleukin-6
Animal Models
Macrophages
Magnetic Resonance Imaging
Diet

ASJC Scopus subject areas

  • Pharmacology

Cite this

Pentoxifylline prevents spontaneous brain ischemia in stroke-prone rats. / Banfi, Cristina; Sironi, Luigi; De Simoni, Grazia; Gelosa, Paolo; Barcella, Simona; Perego, Carlo; Gianazza, Elisabetta; Guerrini, Uliano; Tremoli, Elena; Mussoni, Luciana.

In: Journal of Pharmacology and Experimental Therapeutics, Vol. 310, No. 3, 09.2004, p. 890-895.

Research output: Contribution to journalArticle

Banfi, Cristina ; Sironi, Luigi ; De Simoni, Grazia ; Gelosa, Paolo ; Barcella, Simona ; Perego, Carlo ; Gianazza, Elisabetta ; Guerrini, Uliano ; Tremoli, Elena ; Mussoni, Luciana. / Pentoxifylline prevents spontaneous brain ischemia in stroke-prone rats. In: Journal of Pharmacology and Experimental Therapeutics. 2004 ; Vol. 310, No. 3. pp. 890-895.
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