TGF-β1 Attenuates Spinal Neuroinflammation and the Excitatory Amino Acid System in Rats With Neuropathic Pain

Chen, Nan‐Fu; Huang, Sheng-Lung; Chen, Wu-Fu; Chen, Chunhong; Lu, Ching-Hsiang; Chen, Chunlin; Yang, San‐Nan; Wang, Hui‐Min David; Wen, Zhi‐Hong

doi:10.1016/j.jpain.2013.08.010

Cited by 61 publications

(68 citation statements)

References 112 publications

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“…How does TGF-β1 reduce neuropathic pain? As a major antiinflammatory cytokine, TGF-β1 inhibits the activation and proliferation of microglia and astrocytes and reduces the expression of proinflammatory cytokines in neuropathic pain conditions (30,50). As expected, i.t.…”

Section: Figure 7 Exogenous Tgf-β1 Blocks Cci-induced Increases In Asupporting

confidence: 76%

Intrathecal bone marrow stromal cells inhibit neuropathic pain via TGF-β secretion

Chen¹,

Xie²,

Ji³

2015

J. Clin. Invest.

191

244

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Section: Figure 7 Exogenous Tgf-β1 Blocks Cci-induced Increases In Asupporting

confidence: 76%

Intrathecal bone marrow stromal cells inhibit neuropathic pain via TGF-β secretion

Chen¹,

Xie²,

Ji³

2015

J. Clin. Invest.

191

244

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“…Reduced transport in females is consistent with increased Tnf expression and elevated extracellular lactate levels, which are both associated with impaired glutamate transport in other contexts (20,60). In addition, reduced Tgfb1 expression in females is associated with increased vulnerability to excitotoxicity (23). Lactate is a component of a complex energy homeostasis maintained in the CNS by astrocytes and neurons that may exert both oxidative and metabolic stress following ethanol exposure in females (49).…”

Section: Figurementioning

confidence: 78%

Astrocyte Dysfunction Induced by Alcohol in Females but Not Males

et al. 2015

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Chronic alcohol abuse is associated with brain damage in a sex-specific fashion, but the mechanisms involved are poorly described and remain controversial. Previous results have suggested that astrocyte gene expression is influenced by ethanol intoxication and during abstinence in vivo. Here, bioinformatic analysis of astrocyte-enriched ethanol-regulated genes in vivo revealed ubiquitin pathways as an ethanol target, but with sexually dimorphic cytokine signaling and changes associated with brain aging in females and not males. Consistent with this result, astrocyte activation was observed after exposure in female but not male animals, with reduced S100β levels in the anterior cingulate cortex and increased GFAP(+) cells in the hippocampus. In primary culture, the direct effects of chronic ethanol exposure followed by recovery on sex-specific astrocyte function were examined. Male astrocyte responses were consistent with astrocyte deactivation with reduced GFAP expression during ethanol exposure. In contrast, female astrocytes exhibited increased expression of Tnf, reduced expression of the neuroprotective cytokine Tgfb1, disrupted bioenergetics and reduced excitatory amino acid uptake following exposure or recovery. These results indicate widespread astrocyte dysfunction in ethanol-exposed females and suggest a mechanism that may underlie increased vulnerability to ethanol-induced neurotoxicity in females.

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“…7e8). TGF-b1, a protein of the multifunctional growth factor family, has been previously reported to have roles in antineuropathy and the regulation of homeostasis in local spinal cord microenvironments [41,74,75]. TGF-b1 can suppress activation of microglia and astrocytes [76e78], thereby exerting antineuroinflammatory effects [79].…”

Section: Discussionmentioning

confidence: 99%

“…TGF-b1 can suppress activation of microglia and astrocytes [76e78], thereby exerting antineuroinflammatory effects [79]. These effects have been also implicated in rats with peripheral neuropathy [41,74]. However, the effects of PCD-1 at the posttranscriptional and translational levels (including the effects on TGF-b and mTOR signaling) remain challenging to decipher.…”

Section: Discussionmentioning

confidence: 99%

“…administration of an mTOR inhibitor, rapamycin, or TGF-beta, attenuates nociception in cases of neuropathic pain [39e41]. Zhang et al [42] and Chen et al [41] also reported up-regulation of phosphorylated mTOR (phospho-mTOR) and down-regulation of TGF-b1 in neuropathic rats. However, the antinociceptive effects of PCD-1 on spinal glia, mTOR, and TGF-beta in the context of neuropathy are unclear.…”

Section: Introductionmentioning

confidence: 99%

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The use of the antimicrobial peptide piscidin (PCD)-1 as a novel anti-nociceptive agent

Chen¹,

Huang²,

Liao³

et al. 2015

Biomaterials

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TGF-β1 Attenuates Spinal Neuroinflammation and the Excitatory Amino Acid System in Rats With Neuropathic Pain

Cited by 61 publications

References 112 publications

Intrathecal bone marrow stromal cells inhibit neuropathic pain via TGF-β secretion

Intrathecal bone marrow stromal cells inhibit neuropathic pain via TGF-β secretion

Astrocyte Dysfunction Induced by Alcohol in Females but Not Males

The use of the antimicrobial peptide piscidin (PCD)-1 as a novel anti-nociceptive agent

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