Dataset Information

Stress-Activated Protein Kinases in Spinal Cord Injury: Focus on Roles of p38.

ABSTRACT: Spinal cord injury (SCI) consists of three phases-acute, secondary, and chronic damages-and limiting the development of secondary damage possibly improves functional recovery after SCI. A major component of the secondary phase of SCI is regarded as inflammation-triggered events: induction of cytokines, edema, microglial activation, apoptosis of cells including oligodendrocytes and neurons, demyelination, formation of the astrocytic scar, and so on. Two major stress-activated protein kinases (SAPKs)-c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (p38 MAPK)-are activated in various types of cells in response to cellular stresses such as apoptotic stimuli and inflammatory waves. In animal models of SCI, inhibition of either JNK or p38 has been shown to promote neuroprotection-associated functional recovery. Here, we provide an overview on the roles of SAPKs in SCI and, in particular, the pathological role of p38 will be discussed as a promising target for therapeutic intervention in SCI.

SUBMITTER: Kasuya Y

PROVIDER: S-EPMC5877728 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature

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Stress-Activated Protein Kinases in Spinal Cord Injury: Focus on Roles of p38.

Kasuya Yoshitoshi Y Umezawa Hiroki H Hatano Masahiko M

International journal of molecular sciences 20180315 3

Spinal cord injury (SCI) consists of three phases-acute, secondary, and chronic damages-and limiting the development of secondary damage possibly improves functional recovery after SCI. A major component of the secondary phase of SCI is regarded as inflammation-triggered events: induction of cytokines, edema, microglial activation, apoptosis of cells including oligodendrocytes and neurons, demyelination, formation of the astrocytic scar, and so on. Two major stress-activated protein kinases (SAP ...[more]

PMID: 29543752

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Project description:Spinal cord injury (SCI) is a serious condition that results in irreparable nerve damage and severe loss of motor or sensory function. Resveratrol (3,4',5-trihy- droxystilbene) is a naturally occurring plant-based polyphenol that has demonstrated powerful antioxidative, anti-inflammatory, and anti-carcinogenic pharmaceutical properties in previous studies. In the central nervous system, it promotes neuronal recovery and protects residual function. However, the role of resveratrol in SCI recovery remains elusive. In this study, the potential mechanisms by which resveratrol affect SCI in rats were assessed by constructing a contusion model of SCI. Resveratrol was intraperitoneally administered to rats. Behavioral scores and electrophysiological examinations were performed to assess functional recovery. After magnetic resonance imaging and staining with hematoxylin and eosin (HE) and Luxor Fast Blue (LFB), tissue recovery was analyzed. Immunofluorescence with NeuN and glial fibrillary acidic protein (GFAP) was employed to evaluate neuronal survival and glial changes. TdT-mediated dUTP nick end labeling (TUNEL) assay was performed to examine apoptotic rates. Moreover, network pharmacology was performed to identify relevant pathways of resveratrol for the treatment of SCI. Lastly, ELISA was performed to detect the expression levels of interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), and IL-6. Our findings revealed that resveratrol dramatically improved the hindlimb locomotor function and their electrophysiological outcomes. Notably, lesion size was significantly reduced on magnetic resonance imaging. HE and LFB staining exposed increased sparseness of tissue and myelin. GFAP and NeuN immunofluorescence assays at the lesion site determined that resveratrol boosted neuronal survival and attenuated glial cell overgrowth. In addition, resveratrol reduced the density and number of TUNEL-positive cells in rats after injury. Additionally, gene ontology analysis revealed that the enriched differentially expressed protein was associated with the JNK/p38MAPK (c-jun N-terminal kinase/p38 mitogen-activated protein kinase) signaling pathway. Following resveratrol treatment, the expression levels of IL-1β, TNF-α, and IL-6 were decreased. In summary, the administration of resveratrol protects motor function and neuronal survival in rats after SCI. Furthermore, resveratrol exerts an anti-inflammatory effect by blocking the JNK/p38MAPK signaling pathway.

Dataset Information

Stress-Activated Protein Kinases in Spinal Cord Injury: Focus on Roles of p38.

Publications

Stress-Activated Protein Kinases in Spinal Cord Injury: Focus on Roles of p38.

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