STAT3 is a Critical Regulator of Astrogliosis and Scar Formation after Spinal Cord Injury

Herrmann, Julia; Imura, Tetsuya; Song, Bei; Qi, Jingwei; Ao, Yan; Nguyen, Thu K.; Korsak, Rose A.; Takeda, Kiyoshi; Akira, Shizuo; Sofroniew, Michael V.

doi:10.1523/jneurosci.1709-08.2008

Cited by 792 publications

(899 citation statements)

References 74 publications

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“…Slight increased expression of GFAP, which is an intermediate filament protein of astrocytes and ependymal cells [55][56][57], is indicative of the traumatic effect of RV. Marked GFAP expression is also indicative of reactive astrogliosis [58], which may be detrimental on the long run as it usually underlie neural dysfunction and pathology in certain neurological disease states [59]. GFAP expression however, appeared unaffected in the GL and the RV+GL groups, which supports previous parameter results of the present study.…”

Section: Discussionsupporting

confidence: 89%

Rauwolfia vomitoria and Gongronema latifolium extracts influences cerebellar cortex

Ekong¹,

Nwakanma²

2017

Alzheimers Dement Cogn Neurol

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Oxidative stress and free radical production is an etiology to some neurodegenerative diseases which may be preventable by prior neuronal protection using herbs. Rauwolfia vomitoria and Gongronema latifolium are medicinal herbs with antioxidant, anti-diabetic and analgesic properties among others. While R. vomitoria acts as a brain stimulant, as well as a depressant, neurotoxic effects have also been reported, which G. latifolium has shown the potential to mitigate. This study therefore investigated the effects of the combination of R. vomitoria and G. latifolium on young rats' cerebellar cortex. Twenty young male Wistar rats (100-150 g) were divided equally into 4 groups (n=5). Oral doses of the vehicle (Tween 20™), ethanolic extracts of 200 mg/kg of R. vomitoria (RV), 200 mg/kg of G. latifolium (GL), and the combination of both (RV + GL) were given to the animals for 14 days. On day 15, the animals were sacrificed after ketamine sedation and perfusion-fixed with 10% buffered-formalin. The cerebella were excised and processed for histomorphology by silver impregnation technique and immunolabelled with anti-neuron specific enolase (NSE) and glial fibrillary acidic protein (GFAP). The histology results showed atrophied Purkinje and other neurons with increased NSE and GFAP expressions in the RV group, which were not as such in the GL and RV+GL groups, an indication of cerebellar cortical injury. In conclusion, RV was injurious to the cerebellar cortical neurons and also stimulated NSE and GFAP, but these RV-induced traumas were slightly mitigated with GL combination. This preliminary report of RV+GL combination may be considered an alternative to RV single treatment for better disease management and brain protection.

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Section: Discussionsupporting

confidence: 89%

Rauwolfia vomitoria and Gongronema latifolium extracts influences cerebellar cortex

Ekong¹,

Nwakanma²

2017

Alzheimers Dement Cogn Neurol

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“…An early step of this response is the activation of astrocytes that is necessary to reform a damaged blood-brain barrier, to detoxify toxic substances, and for general wound repair (Faulkner et al, 2004;Herrmann et al, 2008). There is also remodeling of the extracellular matrix manifested by alterations of molecules such as fibronectin by astrocytes (Tom et al, 2004).…”

Section: Resultsmentioning

confidence: 99%

Depletion of Ly6G/Gr-1 Leukocytes after Spinal Cord Injury in Mice Alters Wound Healing and Worsens Neurological Outcome

Stirling¹,

Liu²,

Kubes³

et al. 2009

J. Neurosci.

197

155

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Spinal cord injury (SCI) induces a robust inflammatory response and the extravasation of leukocytes into the injured tissue. To further knowledge of the functions of neuroinflammation in SCI in mice, we depleted the early arriving neutrophils using an anti-Ly6G/Gr-1 antibody. Complete blood counts revealed that neutrophils increased ϳ3-fold over uninjured controls and peaked at 6 -12 h after injury, and that anti-Ly6G/Gr-1 treatment reduced circulating neutrophils by Ͼ90% at these time points. Intravital and spinning disk confocal microscopy of the exposed posterior vein and postcapillary venules showed a significant reduction in rolling and adhering neutrophils in vivo after anti-Ly6G/Gr-1 treatment; this was accompanied by a parallel reduction in neutrophil numbers within the injured spinal cord at 24 and 48 h as determined by flow cytometry. The evolution of astrocyte reactivity, a wound healing response, was reduced in anti-Ly6G/Gr-1-treated mice, which also had less spared white matter and axonal preservation compared with isotype controls. These histological outcomes may be caused by alterations of growth factors and chemokines important in promoting wound healing. Importantly, anti-Ly6G/Gr-1 treatment worsened behavioral outcome as determined using the Basso Mouse Scale and subscores. Although the spectrum of cells affected by anti-Ly6G/Gr-1 antibody treatment cannot be fully ascertained at this point, the correspondence of neutrophil depletion and worsened recovery suggests that neutrophils promote recovery after SCI through wound healing and protective events that limit lesion propagation.

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“…Beside the role in inflammatory signaling pathways (5,22,38), STAT3 functions as a critical mediator of oncogenic signaling through transcriptional activation of genes encoding apoptosis inhibitors (e.g., Bcl-xL, Mcl-1, and survivin), cell cycle regulators (e.g., cyclin D1, Pim-1, and c-Myc), and inducers of angiogenesis (e.g., vascular endothelial growth factor) (4,5,42). Therefore, the activated STAT3 is now considered to play a master regulatory role in the progression and survival of human cancer, thereby being regarded as a promising relevant target for multiple cancer types (5).…”

Section: Discussionmentioning

confidence: 99%

STAT3 Regulation by S-Nitrosylation: Implication for Inflammatory Disease

Kim

Won²,

Singh³

et al. 2014

Antioxidants & Redox Signaling

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Aims: S-nitrosylation and S-glutathionylation, redox-based modifications of protein thiols, are recently emerging as important signaling mechanisms. In this study, we assessed S-nitrosylation-based regulation of Janus-activated kinase 2/signal transducer and activator of transcription 3 ( JAK2/STAT3) pathway that plays critical roles in immune/inflammatory responses and tumorigenesis. Results: Our studies show that STAT3 in stimulated microglia underwent two distinct redox-dependent modifications, S-nitrosylation and S-glutathionylation. STAT3 S-nitrosylation was associated with inducible nitric oxide synthase (iNOS)-produced nitric oxide (NO) and S-nitrosoglutathione (GSNO), whereas S-glutathionylation of STAT3 was associated with cellular oxidative stress. NO produced by iNOS or treatment of microglia with exogenous GSNO inhibited STAT3 activation via inhibiting STAT3 phosphorylation (Tyr 705 ). Consequently, the interleukin-6 (IL-6)-induced microglial proliferation and associated gene expressions were also reduced. In cell-free kinase assay using purified JAK2 and STAT3, STAT3 phosphorylation was inhibited by its selective preincubation with GSNO, but not by preincubation of JAK2 with GSNO, indicating that GSNO-mediated mechanisms inhibit STAT3 phosphorylation through S-nitrosylation of STAT3 rather than JAK2. In this study, we identified that

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STAT3 is a Critical Regulator of Astrogliosis and Scar Formation after Spinal Cord Injury

Cited by 792 publications

References 74 publications

Rauwolfia vomitoria and Gongronema latifolium extracts influences cerebellar cortex

Rauwolfia vomitoria and Gongronema latifolium extracts influences cerebellar cortex

Depletion of Ly6G/Gr-1 Leukocytes after Spinal Cord Injury in Mice Alters Wound Healing and Worsens Neurological Outcome

STAT3 Regulation by S-Nitrosylation: Implication for Inflammatory Disease

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