G-CSF administration is neuroprotective following transient cerebral ischemia even in the absence of a functional NOS-2 gene - PubMed (original) (raw)

G-CSF administration is neuroprotective following transient cerebral ischemia even in the absence of a functional NOS-2 gene

Claire L Gibson et al. J Cereb Blood Flow Metab. 2010 Apr.

Abstract

Granulocyte colony-stimulating factor (G-CSF) is a candidate neuroprotective factor following cerebral ischemia. To determine whether G-CSF acts partly through the inhibition of nitric oxide synthase (NOS)-2 expression, we administered G-CSF to male NOS-2-/- mice after cerebral ischemia. Although male NOS-2-/- mice exhibit resistance to the gross effects of cerebral ischemia, they display neuronal loss and skilled motor deficits following cerebral ischemia. Administration of G-CSF during reperfusion reduced motor deficit and neuronal loss. Thus, G-CSF is still effective in NOS-2 gene-deficient mice, suggesting that part of the mechanism of action is independent of NOS-2.

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Figures

Figure 1

Figure 1

(A) Assessment of rotarod performance showed that after middle cerebral artery occlusion (MCAO), _NOS-2_−/− mice that received granulocyte colony-stimulating factor (G-CSF) or vehicle were indistinguishable from shams. The data are expressed as the percentage (%) of mean duration per day compared with the presurgery control value. (B) Skilled motor performance assessed using the grid test showed that unilateral deficits, measured by the number of contralateral foot faults (expressed as the % of total errors made), were significantly higher in _NOS-2_−/− mice after MCAO compared with shams, ***P<0.0001. # represents a significant difference from sham animals on the day of testing. Treatment with G-CSF significantly reduced this deficit, *P<0.05. After sham surgery, no unilateral functional deficit was observed. (C, D) Neuronal nuclei (NeuN)-positive neurons were identified in the striatal areas and the lateral cortex. (E) Cell counts of NeuN-positive neurons showed that NOS-2−/− mice exhibited neuronal loss 7 days after MCAO (***P<0.001) which was significantly reduced after G-CSF treatment (**P<0.01).

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