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1.
Neuroreport ; 23(13): 786-92, 2012 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-22825006

RESUMO

The potential benefits or the tissue-damaging effects of inflammatory response after central nervous system injuries have long been disputed. Recent studies have noted that substance P (SP), a neuropeptide, plays an important role in the wound-healing process by recruiting bone marrow stem cells to the injured tissue. In this study, we examined whether SP can enhance recovery from spinal cord injury (SCI) in Sprague-Dawley rats through its known function of stem cell mobilization and/or through the modulation of inflammation. We examined proinflammatory and anti-inflammatory cytokines and markers for macrophage subtypes. SP treatment modulated the SCI microenvironment toward a more anti-inflammatory and reparative one by inducing interleukin-10 and M2 macrophages and suppressing inducible nitric oxide synthase and tumor necrosis factor-α. This modulation was achieved at 1 day much earlier than SP-stimulated bone marrow stem cells' mobilization. Early intervention of the devastating inflammatory response by SP treatment caused the lesion cavity to become filled with robust axonal outgrowth that overlaid the M2 macrophages at 2 weeks--all of which culminated in tissue sparing and improvement in functional recovery from the SCI. SP is therefore a potential anti-inflammatory modulator for the treatment of injury-induced inflammatory central nervous system disorders.


Assuntos
Axônios/efeitos dos fármacos , Macrófagos/efeitos dos fármacos , Traumatismos da Medula Espinal/tratamento farmacológico , Substância P/uso terapêutico , Animais , Anti-Inflamatórios/uso terapêutico , Axônios/patologia , Citocinas/metabolismo , Inflamação/tratamento farmacológico , Interleucina-10/metabolismo , Masculino , Microglia/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Recuperação de Função Fisiológica/efeitos dos fármacos , Traumatismos da Medula Espinal/metabolismo , Traumatismos da Medula Espinal/patologia , Substância P/metabolismo , Fator de Necrose Tumoral alfa/metabolismo
2.
J Neurosci ; 27(29): 7751-61, 2007 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-17634369

RESUMO

Spinal cord injury (SCI) causes a permanent neurological disability, and no satisfactory treatment is currently available. After SCI, pro-nerve growth factor (proNGF) is known to play a pivotal role in apoptosis of oligodendrocytes, but the cell types producing proNGF and the signaling pathways involved in proNGF production are primarily unknown. Here, we show that minocycline improves functional recovery after SCI in part by reducing apoptosis of oligodendrocytes via inhibition of proNGF production in microglia. After SCI, the stress-responsive p38 mitogen-activated protein kinase (p38MAPK) was activated only in microglia, and proNGF was produced by microglia via the p38MAPK-mediated pathway. Minocycline treatment significantly reduced proNGF production in microglia in vitro and in vivo by inhibition of the phosphorylation of p38MAPK. Furthermore, minocycline treatment inhibited p75 neurotrophin receptor expression and RhoA activation after injury. Finally, minocycline treatment inhibited oligodendrocyte death and improved functional recovery after SCI. These results suggest that minocycline may represent a potential therapeutic agent for acute SCI in humans.


Assuntos
Antibacterianos/farmacologia , Minociclina/farmacologia , Fatores de Crescimento Neural/metabolismo , Oligodendroglia/efeitos dos fármacos , Traumatismos da Medula Espinal/patologia , Análise de Variância , Animais , Animais Recém-Nascidos , Axônios/patologia , Morte Celular/efeitos dos fármacos , Células Cultivadas , Modelos Animais de Doenças , Regulação da Expressão Gênica/efeitos dos fármacos , Marcação In Situ das Extremidades Cortadas/métodos , Masculino , Atividade Motora/efeitos dos fármacos , Atividade Motora/fisiologia , Bainha de Mielina/metabolismo , Bainha de Mielina/patologia , RNA Mensageiro/metabolismo , Ratos , Ratos Sprague-Dawley , Reação em Cadeia da Polimerase Via Transcriptase Reversa/métodos , Fator Rho/metabolismo
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