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Involvement of ERK2 in traumatic spinal cord injury.

ABSTRACT: Activation of extracellular signal-regulated protein kinase 1/2 (ERK1/2) are implicated in the pathophysiology of spinal cord injury (SCI). However, the specific functions of individual ERK isoforms in neurodegeneration are largely unknown. We investigated the hypothesis that ERK2 activation may contribute to pathological and functional deficits following SCI and that ERK2 knockdown using RNA interference may provide a novel therapeutic strategy for SCI. Lentiviral ERK2 shRNA and siRNA were utilized to knockdown ERK2 expression in the spinal cord following SCI. Pre-injury intrathecal administration of ERK2 siRNA significantly reduced excitotoxic injury-induced activation of ERK2 (p < 0.001) and caspase 3 (p < 0.01) in spinal cord. Intraspinal administration of lentiviral ERK2 shRNA significantly reduced ERK2 expression in the spinal cord (p < 0.05), but did not alter ERK1 expression. Administration of the lentiviral ERK2 shRNA vector 1 week prior to severe spinal cord contusion injury resulted in a significant improvement in locomotor function (p < 0.05), total tissue sparing (p < 0.05), white matter sparing (p < 0.05), and gray matter sparing (p < 0.05) 6 weeks following severe contusive SCI. Our results suggest that ERK2 signaling is a novel target associated with the deleterious consequences of spinal injury.

SUBMITTER: Yu CG

PROVIDER: S-EPMC4048743 | biostudies-literature | 2010 Apr

REPOSITORIES: biostudies-literature

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Involvement of ERK2 in traumatic spinal cord injury.

Yu Chen-Guang CG Yezierski Robert P RP Joshi Aashish A Raza Kashif K Li Yanzhang Y Geddes James W JW

Journal of neurochemistry 20100112 1

Activation of extracellular signal-regulated protein kinase 1/2 (ERK1/2) are implicated in the pathophysiology of spinal cord injury (SCI). However, the specific functions of individual ERK isoforms in neurodegeneration are largely unknown. We investigated the hypothesis that ERK2 activation may contribute to pathological and functional deficits following SCI and that ERK2 knockdown using RNA interference may provide a novel therapeutic strategy for SCI. Lentiviral ERK2 shRNA and siRNA were util ...[more]

PMID: 20067580

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Project description:ObjectiveDespite understanding the associated adverse outcomes, identifying hospitalized patients at risk for sepsis is challenging. The authors aimed to characterize the epidemiology and clinical risk of sepsis in patients who underwent vertebral fracture repair for traumatic spinal injury (TSI).MethodsThe authors conducted a retrospective cohort analysis of adults undergoing vertebral fracture repair during initial hospitalization after TSI who were registered in the National Trauma Data Bank from 2011 to 2014.ResultsOf the 29,050 eligible patients undergoing vertebral fracture repair, 317 developed sepsis during initial hospitalization. Of these patients, most presented after a motor vehicle accident (63%) or fall (28%). Patients in whom sepsis developed had greater odds of being male (adjusted OR [aOR] 1.5, 95% CI 1.1-1.9), having diabetes mellitus (aOR 1.5, 95% CI 1.11-2.1), and being obese (aOR 1.9, 95% CI 1.4-2.5). Additionally, they had greater odds of presenting with moderate (aOR 2.7, 95% CI 1.8-4.2) or severe (aOR 3.9, 95% CI 2.9-5.2) Glasgow Coma Scale scores and of having concomitant abdominal injuries (aOR 1.9, 95% CI 1.5-2.5) but not cranial, thoracic, or lower-extremity injuries. Interestingly, cervical spine injury was significantly associated with developing sepsis (OR 1.4, 95% CI 1.1-1.8), but thoracic and lumbar spine injuries were not. Spinal cord injury (OR 1.9, 95% CI 1.5-2.5) was also associated with sepsis regardless of level. Patients with sepsis were hospitalized approximately 16 days longer. They had greater odds of being discharged to rehabilitative care or home with rehabilitative care (OR 2.4, 95% CI 1.8-3.2) and greater odds of death or discharge to hospice (OR 6.0, 95% CI 4.4-8.1).ConclusionsAmong patients undergoing vertebral fracture repair, those with cervical spine fractures, spinal cord injuries, preexisting comorbidities, and severe concomitant injuries are at highest risk for developing postoperative sepsis and experiencing adverse hospital disposition.

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Involvement of ERK2 in traumatic spinal cord injury.

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Involvement of ERK2 in traumatic spinal cord injury.

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