Allopurinol administered after inducing hypoxia-ischemia reduces brain injury in 7-day-old rats

Charles Palmer, Javad Towfighi, Rebecca L. Roberts, Daniel F. Heitjan

Research output: Contribution to journalArticle

145 Citations (Scopus)

Abstract

We determined that treatment of immature rats with allopurinol at 15 min after cerebral hypoxia-ischemia reduces brain damage. Seven-d postnatal rats were subjected to right common carotid artery ligation followed by 2.25 h of hypoxia (8% 02). At 15 min of recovery in room air, the rat pups received either allopurinol (135 mg/kg s.c.) or saline. Some of the rats (n = 65) were killed at 42 h of recovery for measurement of cerebral hemispheric water content. Other animals (n = 63) were killed at 30 d for morphologic assessment of the severity of damage. In separate rats, we measured the levels of allopurinol and its metabolites in serum and in the brain around the time of peak serum levels. We also determined the effect of allopurinol on rat pup body temperature. Allopurinol reduced the increase in right hemisphere water content and markedly reduced atrophy. No cavitary lesions were seen in the 31 allopurinol-treated rats, whereas 15 of 32 saline-treated rats had cavitary cerebral lesions. Histologic examination confirmed that the allopurinol-treated rats had less brain injury. Serum allopurinol and oxypurinol peaked between 0.5 and 1 h after allopurinol injection. Their peak serum concentrations at 0.75 h postinjection combined was between 360 and 510 µM. Allopurinol did not lower rectal temperature more than 0.04°C. In conclusion, high-dose allopurinol administered at 15 min of recovery from cerebral hypoxia-ischemia markedly reduces both acute brain edema and long-term cerebral injury in immature rats.

Original languageEnglish (US)
Pages (from-to)405-411
Number of pages7
JournalPediatric Research
Volume33
Issue number4
StatePublished - Jan 1 1993

Fingerprint

Allopurinol
Brain Injuries
Ischemia
Brain Hypoxia-Ischemia
Serum
Hypoxia
Oxypurinol
Recovery Room
Water
Common Carotid Artery
Brain Edema
Brain
Body Temperature
Atrophy
Ligation
Air

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health

Cite this

Allopurinol administered after inducing hypoxia-ischemia reduces brain injury in 7-day-old rats. / Palmer, Charles; Towfighi, Javad; Roberts, Rebecca L.; Heitjan, Daniel F.

In: Pediatric Research, Vol. 33, No. 4, 01.01.1993, p. 405-411.

Research output: Contribution to journalArticle

Palmer, Charles ; Towfighi, Javad ; Roberts, Rebecca L. ; Heitjan, Daniel F. / Allopurinol administered after inducing hypoxia-ischemia reduces brain injury in 7-day-old rats. In: Pediatric Research. 1993 ; Vol. 33, No. 4. pp. 405-411.
@article{f06df6f936844ac388cf44af4371f4f1,
title = "Allopurinol administered after inducing hypoxia-ischemia reduces brain injury in 7-day-old rats",
abstract = "We determined that treatment of immature rats with allopurinol at 15 min after cerebral hypoxia-ischemia reduces brain damage. Seven-d postnatal rats were subjected to right common carotid artery ligation followed by 2.25 h of hypoxia (8{\%} 02). At 15 min of recovery in room air, the rat pups received either allopurinol (135 mg/kg s.c.) or saline. Some of the rats (n = 65) were killed at 42 h of recovery for measurement of cerebral hemispheric water content. Other animals (n = 63) were killed at 30 d for morphologic assessment of the severity of damage. In separate rats, we measured the levels of allopurinol and its metabolites in serum and in the brain around the time of peak serum levels. We also determined the effect of allopurinol on rat pup body temperature. Allopurinol reduced the increase in right hemisphere water content and markedly reduced atrophy. No cavitary lesions were seen in the 31 allopurinol-treated rats, whereas 15 of 32 saline-treated rats had cavitary cerebral lesions. Histologic examination confirmed that the allopurinol-treated rats had less brain injury. Serum allopurinol and oxypurinol peaked between 0.5 and 1 h after allopurinol injection. Their peak serum concentrations at 0.75 h postinjection combined was between 360 and 510 µM. Allopurinol did not lower rectal temperature more than 0.04°C. In conclusion, high-dose allopurinol administered at 15 min of recovery from cerebral hypoxia-ischemia markedly reduces both acute brain edema and long-term cerebral injury in immature rats.",
author = "Charles Palmer and Javad Towfighi and Roberts, {Rebecca L.} and Heitjan, {Daniel F.}",
year = "1993",
month = "1",
day = "1",
language = "English (US)",
volume = "33",
pages = "405--411",
journal = "Pediatric Research",
issn = "0031-3998",
publisher = "Lippincott Williams and Wilkins",
number = "4",

}

TY - JOUR

T1 - Allopurinol administered after inducing hypoxia-ischemia reduces brain injury in 7-day-old rats

AU - Palmer, Charles

AU - Towfighi, Javad

AU - Roberts, Rebecca L.

AU - Heitjan, Daniel F.

PY - 1993/1/1

Y1 - 1993/1/1

N2 - We determined that treatment of immature rats with allopurinol at 15 min after cerebral hypoxia-ischemia reduces brain damage. Seven-d postnatal rats were subjected to right common carotid artery ligation followed by 2.25 h of hypoxia (8% 02). At 15 min of recovery in room air, the rat pups received either allopurinol (135 mg/kg s.c.) or saline. Some of the rats (n = 65) were killed at 42 h of recovery for measurement of cerebral hemispheric water content. Other animals (n = 63) were killed at 30 d for morphologic assessment of the severity of damage. In separate rats, we measured the levels of allopurinol and its metabolites in serum and in the brain around the time of peak serum levels. We also determined the effect of allopurinol on rat pup body temperature. Allopurinol reduced the increase in right hemisphere water content and markedly reduced atrophy. No cavitary lesions were seen in the 31 allopurinol-treated rats, whereas 15 of 32 saline-treated rats had cavitary cerebral lesions. Histologic examination confirmed that the allopurinol-treated rats had less brain injury. Serum allopurinol and oxypurinol peaked between 0.5 and 1 h after allopurinol injection. Their peak serum concentrations at 0.75 h postinjection combined was between 360 and 510 µM. Allopurinol did not lower rectal temperature more than 0.04°C. In conclusion, high-dose allopurinol administered at 15 min of recovery from cerebral hypoxia-ischemia markedly reduces both acute brain edema and long-term cerebral injury in immature rats.

AB - We determined that treatment of immature rats with allopurinol at 15 min after cerebral hypoxia-ischemia reduces brain damage. Seven-d postnatal rats were subjected to right common carotid artery ligation followed by 2.25 h of hypoxia (8% 02). At 15 min of recovery in room air, the rat pups received either allopurinol (135 mg/kg s.c.) or saline. Some of the rats (n = 65) were killed at 42 h of recovery for measurement of cerebral hemispheric water content. Other animals (n = 63) were killed at 30 d for morphologic assessment of the severity of damage. In separate rats, we measured the levels of allopurinol and its metabolites in serum and in the brain around the time of peak serum levels. We also determined the effect of allopurinol on rat pup body temperature. Allopurinol reduced the increase in right hemisphere water content and markedly reduced atrophy. No cavitary lesions were seen in the 31 allopurinol-treated rats, whereas 15 of 32 saline-treated rats had cavitary cerebral lesions. Histologic examination confirmed that the allopurinol-treated rats had less brain injury. Serum allopurinol and oxypurinol peaked between 0.5 and 1 h after allopurinol injection. Their peak serum concentrations at 0.75 h postinjection combined was between 360 and 510 µM. Allopurinol did not lower rectal temperature more than 0.04°C. In conclusion, high-dose allopurinol administered at 15 min of recovery from cerebral hypoxia-ischemia markedly reduces both acute brain edema and long-term cerebral injury in immature rats.

UR - http://www.scopus.com/inward/record.url?scp=0027499214&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0027499214&partnerID=8YFLogxK

M3 - Article

C2 - 8479823

AN - SCOPUS:0027499214

VL - 33

SP - 405

EP - 411

JO - Pediatric Research

JF - Pediatric Research

SN - 0031-3998

IS - 4

ER -