Ibuprofen for neuroprotection after cerebral ischemia

Yusuke Iwata, Olivier Nicole, David Zurakowski, Toru Okamura, Richard A. Jonas
The Journal of Thoracic and Cardiovascular Surgery. 2010-02-01; 139(2): 489-493
DOI: 10.1016/j.jtcvs.2009.05.049

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1. J Thorac Cardiovasc Surg. 2010 Feb;139(2):489-93. doi:
10.1016/j.jtcvs.2009.05.049. Epub 2009 Oct 23.

Ibuprofen for neuroprotection after cerebral ischemia.

Iwata Y(1), Nicole O, Zurakowski D, Okamura T, Jonas RA.

Author information:
(1)Children’s National Heart Institute, Children’s National Medical Center,
Washington, DC 20010, USA.

OBJECTIVE: Ibuprofen has been shown to reduce cerebral ischemic injury, such as
may occur after deep hypothermic circulatory arrest. We investigated whether
ibuprofen has direct protective effects against excitotoxic neuronal injury, as
may be seen after cerebral ischemia, by using a cell culture model.
METHODS: Mixed cortical cultures containing neuronal and glial cells were
prepared from fetal mice at 13 to 15 days gestation, plated on a layer of
confluent astrocytes from 1- to 3-day-old postnatal pups. Near-pure neuronal
cultures containing less than 5% astrocytes were obtained from mice of the same
gestational stage. Slowly triggered excitotoxic injury was induced at 37 degrees
C by 24-hour exposure to 12.5 micromol/L N-methyl-D-aspartate or 50 micromol/L
kainate. Neuronal death was quantified by release of lactate dehydrogenase from
damaged cells. Data were analyzed using 1-way analysis of variance with Tukey
post hoc multiple comparisons.
RESULTS: In mixed cultures, ibuprofen concentrations of 25 microg/mL, 50
microg/mL, and 100 microg/mL all significantly reduced
N-methyl-D-aspartate-induced neuronal cell death from 74.5% to 56.1%, 38.7%, and
12.3%, respectively, revealing a strong dose response (P < .001). In near-pure
cultures, ibuprofen at a concentration of 25 microg/mL failed to protect neurons,
indicating that the neuroprotective effects of ibuprofen require interaction with
glial cells. Furthermore, ibuprofen at 100 microg/mL was not protective against
neuronal cell death induced by kainate excitotoxicity in near-pure culture but
was effective in mixed cultures.
CONCLUSION: Ibuprofen provides neuroprotection through glial cells against
excitotoxic neuronal injury caused by glutamatergic excitotoxicity after cerebral
ischemia as demonstrated by reduced neuronal cell death in mixed cell cultures.
Further studies are needed to evaluate the potential of ibuprofen to reduce
neurologic injury in patients experiencing an hypoxic/ischemic insult.

2010 The American Association for Thoracic Surgery. Published by Mosby, Inc. All
rights reserved.

DOI: 10.1016/j.jtcvs.2009.05.049
PMCID: PMC2850810
PMID: 19853865 [Indexed for MEDLINE]


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