PT  - JOURNAL ARTICLE
AU  - Banfi, Cristina
AU  - Sironi, Luigi
AU  - De Simoni, Grazia
AU  - Gelosa, Paolo
AU  - Barcella, Simona
AU  - Perego, Carlo
AU  - Gianazza, Elisabetta
AU  - Guerrini, Uliano
AU  - Tremoli, Elena
AU  - Mussoni, Luciana
TI  - Pentoxifylline Prevents Spontaneous Brain Ischemia in Stroke-Prone Rats
AID  - 10.1124/jpet.104.067090
DP  - 2004 Sep 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 890--895
VI  - 310
IP  - 3
4099  - http://jpet.aspetjournals.org/content/310/3/890.short
4100  - http://jpet.aspetjournals.org/content/310/3/890.full
SO  - J Pharmacol Exp Ther2004 Sep 01; 310
AB  - 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. The American Society for Pharmacology and Experimental Therapeutics