Pre-ischemic treatment of pentoxifylline reduces infarct volumes in transient focal cerebral ischemia in the rat

ABSTRACT

Pentoxifylline [PTX] is used in human for intermittent claudication and cerebral vascular disorders including cerebrovascular dementia. It also inhibits the synthesis of tumor necrosis factor- TNF-alpha], which is believed to be neurotoxic in animal models of cerebral ischemia. The objective of this study was to examine the role of PTX on ischemia/reperfusion injures in rat model of transient focal cerebral ischemia induced by middle cerebral artery occlusion [MCAO]. Male Sprague Dawley rats [n=31] were assigned to sham, saline or PTX [30 or 60 mg/kg]-treated groups. Ischemia was induced by MCAO, followed by 24-hrs reperfusion. Intraperitoneal saline or PTX was administered at 30 min before ischemia. Neurological deficit score test [NDS] was performed after 24-hrs, and the animals was sacrificed for evaluation of cortical and striatal infarct volumes using triphenyltetrazolium chloride staining. The sham group did not have neural dysfunction or cerebral infarction. Cortical infarct volumes in 30 or 60 mg/kg PTX-treated groups, 149 +/- 12 and 129 +/- 19 mm3 respectively, were significantly lower than that of saline-treated group [208 +/- 12 mm 3]. Similar results were also obtained about the striatal infarct volumes [39 +/- 5 and 40 +/- 6 vs. 58 +/- 5 mm 3]. However, there was no significant difference among the neurological dysfunctions from saline and PTX-treated rats. The results of this study indicate that pentoxifylline reduced cerebral infarctions, possibly by diminishing the TNF-alpha-induced neurotoxicity in transient focal cerebral ischemia. This finding also suggests that pentoxifylline might be suitable for clinical trials