Pentoxifylline attenuates hypoxic-ischemic brain injury in immature rats

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

Research output: Contribution to journalArticle

51 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

Fingerprint

Pentoxifylline
Brain Injuries
Infarction
Phosphodiesterase Inhibitors
Platelet Activating Factor
Incidence
Cerebral Infarction
Phosphoric Diester Hydrolases
Wounds and Injuries
Brain Ischemia
Ligation
Heart Diseases
Therapeutics
Ischemia
Tumor Necrosis Factor-alpha
Brain

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health

Cite this

Pentoxifylline attenuates hypoxic-ischemic brain injury in immature rats. / Eun, Baik-Lin; Liu, Xiao Hong; Barks, John D.E.

In: Pediatric Research, Vol. 47, No. 1, 01.01.2000, p. 73-78.

Research output: Contribution to journalArticle

Eun, Baik-Lin ; Liu, Xiao Hong ; Barks, John D.E. / Pentoxifylline attenuates hypoxic-ischemic brain injury in immature rats. In: Pediatric Research. 2000 ; Vol. 47, No. 1. pp. 73-78.
@article{2c7ba44b01714c64826c27332fb0ba83,
title = "Pentoxifylline attenuates hypoxic-ischemic brain injury in immature rats",
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.",
author = "Baik-Lin Eun and Liu, {Xiao Hong} and Barks, {John D.E.}",
year = "2000",
month = "1",
day = "1",
language = "English",
volume = "47",
pages = "73--78",
journal = "Pediatric Research",
issn = "0031-3998",
publisher = "Lippincott Williams and Wilkins",
number = "1",

}

TY - JOUR

T1 - Pentoxifylline attenuates hypoxic-ischemic brain injury in immature rats

AU - Eun, Baik-Lin

AU - Liu, Xiao Hong

AU - Barks, John D.E.

PY - 2000/1/1

Y1 - 2000/1/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=0033971868&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0033971868&partnerID=8YFLogxK

M3 - Article

C2 - 10625085

AN - SCOPUS:0033971868

VL - 47

SP - 73

EP - 78

JO - Pediatric Research

JF - Pediatric Research

SN - 0031-3998

IS - 1

ER -