homeostasis/metabolism
• at 1-7 days after acute brain (cortical stab) injury, homozygotes show significantly reduced levels of hypertrophic changes in astrocytes, microglial accumulation, and neuronal death relative to wild-type controls
• in addition, activation of the IL-6/signal transducer and activator of transcription 3 (STAT3) pathway, including the expression of IL-6 family cytokines and phosphorylation of STAT3, is markedly decreased relative to wild-type controls
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nervous system
• at day 4 after cortical stab injury, homozygotes display attenuated neuronal death in the wounded area, as shown by Fluoro-Jade C staining and ssDNA immunostaining, which detect apoptotic cells and degenerating neurons, respectively
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• at day 4 after cortical stab injury, homozygotes display significantly lower GFAP protein levels and GFAP signal intensity in all regions within 400 um from the injury site relative to wild-type controls
• at day 1 after cortical stab injury, IL-6-positive astrocytes are detected less often in the lesion site relative to wild-type controls
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• after cortical stab injury, homozygotes display a lower induction of reactive astroglial and microglial markers in the injured cortex relative to wild-type controls, indicating an impaired glial response
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• at day 4 after cortical stab injury, homozygotes show a significantly lower number of Iba1-positive microglia in regions closer to the injury site than wild-type controls, indicating reduced microglial recruitment
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• after astroglial activation by forskolin treatment, cultured astrocytes derived from mutant mice show a significantly lower level of induction of Il6 and Gfap at 8 h and 24 h post-treatment, respectively, relative to similarly treated wild-type astrocytes
• adenovirus-mediated re-expression of Ndrg2 in mutant astrocytes fully rescues the reduction of IL-6 expression after forskolin stimulation at both mRNA and protein levels, while the restoration in Gfap expression is milder
• however, untreated mutant astrocytes show normal proliferation and migration as determined by a MTT reduction assay and scratch wound assay, respectively
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immune system
• at day 4 after cortical stab injury, homozygotes show a significantly lower number of Iba1-positive microglia in regions closer to the injury site than wild-type controls, indicating reduced microglial recruitment
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• at day 1 after cortical stab injury, homozygotes show a tendency towards decreased IL-6 protein levels as determined by ELISA, with 37.4 pg/mL versus 24.4 pg/mL in the ipsilateral side in wild-type controls
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• at day 1 and/or day 4 after cortical stab injury, homozygotes display significantly lower mRNA expression levels of inflammatory mediators relative to wild-type controls
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cellular
• at day 4 after cortical stab injury, homozygotes display attenuated neuronal death in the wounded area, as shown by Fluoro-Jade C staining and ssDNA immunostaining, which detect apoptotic cells and degenerating neurons, respectively
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• at day 4 after cortical stab injury, homozygotes show a significantly lower number of Iba1-positive microglia in regions closer to the injury site than wild-type controls, indicating reduced microglial recruitment
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hematopoietic system
• at day 4 after cortical stab injury, homozygotes show a significantly lower number of Iba1-positive microglia in regions closer to the injury site than wild-type controls, indicating reduced microglial recruitment
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