Abstract:
OBJECTIVE:To investigate whether inhibition of cyclooxygenase-2, a critical component of the inflammatory pathway, is neuroprotective in a neonatal rat model of cerebral hypoxia-ischemia. The development of brain inflammation largely contributes to neonatal brain injury that may lead to a lifetime of neurologic deficits. DESIGN:Laboratory investigation. SETTING:University research laboratory. SUBJECTS:Postnatal day ten Sprague-Dawley rats. INTERVENTIONS:Neonatal hypoxia-ischemia was induced by ligation of the right common carotid artery followed by 2 hrs of hypoxia (8% oxygen). The pups in treatment groups were administered 10 mg/kg (low dose) or 30 mg/kg (high dose) of a known selective cyclooxygenase-2 inhibitor (NS398). Animals were euthanized at three time points: 72 hrs, 2 wks, or 6 wks. Inflammation outcomes were assessed at 72 hrs; brain damage was assessed at 2 wks and 6 wks along with other organs (heart, spleen). Detailed neurobehavioral examination was performed at 6 wks. MEASUREMENTS AND MAIN RESULTS:Pharmacologic inhibition of cyclooxygenase-2 markedly increased survivability within the first 72 hrs compared with untreated rats (100% vs. 72%). Low- and high-dose NS398 significantly attenuated the loss of brain and body weights observed after hypoxia-ischemia. Neurobehavioral outcomes were significantly improved in some parameters with low-dose treatment, whereas high-dose treatment consistently improved all neurologic deficits. Immunohistochemical results showed a marked decrease in macrophage, microglial, and neutrophil abundance in ipsilateral hemisphere of the NS398-treated group along with a reduction in interleukin-6 expression. CONCLUSIONS:Selective cyclooxygenase-2 inhibition protected neonatal rats against death, progression of brain injury, growth retardation, and neurobehavioral deficits after a hypoxic-ischemic insult.
journal_name
Crit Care Medjournal_title
Critical care medicineauthors
Fathali N,Ostrowski RP,Lekic T,Jadhav V,Tong W,Tang J,Zhang JHdoi
10.1097/CCM.0b013e3181cb1158subject
Has Abstractpub_date
2010-02-01 00:00:00pages
572-8issue
2eissn
0090-3493issn
1530-0293journal_volume
38pub_type
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journal_title:Critical care medicine
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doi:10.1097/00003246-199112000-00012
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doi:10.1097/00003246-199801000-00033
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pub_type: 杂志文章,评审
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更新日期:2007-08-01 00:00:00
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更新日期:2007-02-01 00:00:00
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更新日期:2010-02-01 00:00:00
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doi:10.1097/00003246-199703000-00002
更新日期:1997-03-01 00:00:00
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更新日期:2003-11-01 00:00:00
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更新日期:2009-03-01 00:00:00
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doi:10.1097/CCM.0b013e3181760e5d
更新日期:2008-06-01 00:00:00
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doi:10.1097/01.CCM.0000245783.28478.AD
更新日期:2006-12-01 00:00:00
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更新日期:2017-12-01 00:00:00
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pub_type: 临床试验,杂志文章,随机对照试验
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更新日期:2010-02-01 00:00:00
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更新日期:2001-01-01 00:00:00
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更新日期:2020-10-01 00:00:00
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更新日期:2020-05-01 00:00:00
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更新日期:1984-10-01 00:00:00
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更新日期:2017-08-01 00:00:00
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更新日期:2008-09-01 00:00:00
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更新日期:1984-11-01 00:00:00
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更新日期:2008-06-01 00:00:00