Intracisternal Application of Endotoxin Enhances the Susceptibility to Subsequent Hypoxic-Ischemic Brain Damage in Neonatal Rats
| Autor: | A. Coumans, Johannes Middelanis, Arne Jensen, Richard Berger, Tom H.M. Hasaart, Monika U. von Duering, Stephen L. Leib, Yves Garnier, Hans-Martin Vaihinger |
|---|---|
| Rok vydání: | 2003 |
| Předmět: |
Lipopolysaccharides
Male medicine.medical_specialty Pathology Ischemia Brain damage Internal medicine medicine.artery Cisterna Magna medicine Animals Common carotid artery Rats Wistar Cell damage Injections Intraventricular Asphyxia business.industry Brain Hypoxia (medical) medicine.disease Rats Endocrinology Animals Newborn Hypoxia-Ischemia Brain Pediatrics Perinatology and Child Health Female Tumor necrosis factor alpha Disease Susceptibility medicine.symptom Ligation business |
| Zdroj: | Pediatric Research. 53:770-775 |
| ISSN: | 1530-0447 0031-3998 |
| DOI: | 10.1203/01.pdr.0000059221.40073.82 |
| Popis: | Perinatal brain damage is associated not only with hypoxic-ischemic insults but also with intrauterine inflammation. A combination of antenatal inflammation and asphyxia increases the risk of cerebral palsy >70 times. The aim of the present study was to determine the effect of intracisternal (i.c.) administration of endotoxin [lipopolysaccharides (LPS)] on subsequent hypoxic-ischemic brain damage in neonatal rats. Seven-day-old Wistar rats were subjected to i.c. application of NaCl or LPS (5 microg/pup). One hour later, the left common carotid artery was exposed through a midline neck incision and ligated with 6-0 surgical silk. After another hour of recovery, the pups were subjected to a hypoxic gas mixture (8% oxygen/92% nitrogen) for 60 min. The animals were randomized to four experimental groups: 1) sham control group, left common carotid artery exposed but not ligated (n = 5); 2) LPS group, subjected to i.c. application of LPS (n = 7); 3) hypoxic-ischemic study group, i.c. injection of NaCl and exposure to hypoxia after ligation of the left carotid artery (n = 17); or 4) hypoxic-ischemic/LPS study group, i.c. injection of LPS and exposure to hypoxia after ligation of the left carotid artery (n = 19). Seven days later, neonatal brains were assessed for neuronal cell damage. In a second set of experiments, rat pups received an i.c. injection of LPS (5 microg/pup) and were evaluated for tumor necrosis factor-alpha expression by immunohistochemistry. Neuronal cell damage could not be observed in the sham control or in the LPS group. In the hypoxic-ischemic/LPS group, neuronal injury in the cerebral cortex was significantly higher than in animals that were subjected to hypoxia/ischemia after i.c. application of NaCl. Injecting LPS intracisternally caused a marked expression of tumor necrosis factor-alpha in the leptomeninges. Applying LPS intracisternally sensitizes the immature rat brain to a subsequent hypoxic-ischemic insult. |
| Databáze: | OpenAIRE |
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