Anti-neutrophil antibody enhances the neuroprotective effects of G-CSF by decreasing number of neutrophils in hypoxic ischemic neonatal rat model

抗中性粒细胞抗体通过减少缺氧缺血新生大鼠模型中的中性粒细胞数量增强 G-CSF 的神经保护作用

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作者:Desislava M Doycheva, Tiffany Hadley, Li Li, Richard L Applegate 2nd, John H Zhang, Jiping Tang

Conclusion

Our data suggest that coadministration of G-CSF with Ab not only prevented brain atrophy but also significantly improved neurological function by decreasing blood neutrophil counts. Hence the neuroprotective effects of G-CSF may be further enhanced if neutrophilia is avoided.

Methods

Rat pups were subjected to unilateral carotid artery ligation followed by 2.5h of hypoxia. Animals were randomly assigned to five groups: Sham (n=15), vehicle (HI, n=15), HI with G-CSF treatment (n=15), HI with G-CSF+Ab treatment (n=15), and HI with Ab treatment (n=15). Ab (325μg/kg) was administered intraperitoneally while G-CSF (50μg/kg) was administered subcutaneously 1h post HI followed by daily injections for 3 consecutive days. Animals were euthanized at 96h post HI for blood neutrophil counts and brain infarct volume measurements as well as at 5weeks for neurological function testing and brain weight measurements. Lung and spleen weights at both time points were further analyzed.

Results

The G-CSF treatment group showed tendencies to reduce infarct volume and improve neurological function while significantly increasing neutrophil counts. On the other hand, the G-CSF+Ab group significantly reduced infarct volume, improved neurological function and decreased neutrophil counts. The Ab alone group showed reversal of the neuroprotective effects of the G-CSF+Ab group. No significant differences were found in peripheral organ weights between groups.

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