Pentoxifylline attenuates hypoxic-ischemic brain injury in immature rats

Baik Lin Eun, Xiao Hong Liu, John D.E. Barks

Research output: Contribution to journalArticle

52 Citations (Scopus)

Abstract

Inflammatory mediators are implicated in the pathogenesis of ischemic injury in immature brain. The phosphodiesterase inhibitor pentoxifylline inhibits production of tumor necrosis factor-α and platelet-activating factor. We hypothesized that pentoxifylline treatment would attenuate hypoxic-ischemic brain injury in immature rats. Seven-day-old rats (n = 79) underwent right carotid ligation, followed by hypoxia (F(i)O2 = 0.08). Rats received pentoxifylline immediately before and again after hypoxia (two doses, 25-150 mg/kg/dose, n = 34), or vehicle (n = 27). In separate experiments, rats received pentoxifylline treatment (40 mg/kg/dose, n = 8), or vehicle (n = 10) immediately and again 3 h after hypoxia-ischemia. Severity of injury was assessed 5 d later by visual evaluation of ipsilateral hemisphere infarction and by measurement of bilateral hemispheric cross- sectional areas. Pentoxifylline pretreatment reduced the incidence of liquefactive cerebral infarction, from 75% in controls to 10% with pentoxifylline, 40 mg/kg/dose (p < 0.001, χ2 trend test). Quantification of hemispheric areas confirmed these findings. In contrast, posthypoxic-ischemic treatment with pentoxifylline resulted in only a modest reduction in cortical damage, without an overall reduction in incidence of infarction. Phosphodiesterase inhibition may be an effective strategy to use to decrease the severity of neonatal hypoxic-ischemic brain injury. Pretreatment regimens could be clinically relevant in settings in which an increased risk of cerebral ischemia can be anticipated, such as in infants undergoing surgery to correct congenital heart disease.

Original languageEnglish
Pages (from-to)73-78
Number of pages6
JournalPediatric Research
Volume47
Issue number1
Publication statusPublished - 2000 Jan 1

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health

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