RT Journal Article
SR Electronic
T1 Pentoxifylline Prevents Spontaneous Brain Ischemia in Stroke-Prone Rats
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 890
OP 895
DO 10.1124/jpet.104.067090
VO 310
IS 3
A1 Banfi, Cristina
A1 Sironi, Luigi
A1 De Simoni, Grazia
A1 Gelosa, Paolo
A1 Barcella, Simona
A1 Perego, Carlo
A1 Gianazza, Elisabetta
A1 Guerrini, Uliano
A1 Tremoli, Elena
A1 Mussoni, Luciana
YR 2004
UL http://jpet.aspetjournals.org/content/310/3/890.abstract
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