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      Time is spine: a review of translational advances in spinal cord injury.

      1 , 2 , 1 , 2 , 3 , 1 , 2 , 3
      Journal of neurosurgery. Spine
      Journal of Neurosurgery Publishing Group (JNSPG)
      AIS = ASIA Impairment Scale, ASIA = American Spinal Injury Association, AUC = area under the curve, BSCB = blood–spinal cord barrier, CCS = central cord syndrome, CELLTOP = Adipose Stem Cells for Traumatic Spinal Cord Injury, CNS = central nervous system, CSF = cerebrospinal fluid, CSPG = chondroitin sulfate proteoglycan, CST = corticospinal tract, Cmax = maximum concentration, DTI = diffusion tensor imaging, ESC = embryonic stem cell, FES = functional electrical stimulation, FIM = Functional Independence Measure, G-CSF = granulocyte colony stimulating factor, GFAP = glial fibrillary acidic protein, GRASSP = Graded Redefined Assessment of Strength Sensibility and Prehension, HAMC = hyaluronan/methylcellulose, HGF = hepatocyte growth factor, IL = interleukin, IV = intravenous, MASC = Minocycline in Acute Spinal Cord Injury, MCP = monocyte chemotactic protein, MPSS = methylprednisolone sodium succinate, MSC = mesenchymal stem cell, MT = magnetization transfer, MTR = MT ratio, NSC = neural stem cell, OEC = olfactory ensheathing cell, OPC = oligodendrocyte progenitor cell, RCT = randomized controlled trial, RISCIS = Riluzole in Acute Spinal Cord Injury Study, SCI = spinal cord injury, SCIM = Spinal Cord Independence Measure, SCING = Spinal Cord Injury Neuroprotection with Glyburide, STASCIS = Surgical Timing in Acute Spinal Cord Injury Study, TNF = tumor necrosis factor, Tmax = time to Cmax, aFGF = acidic fibroblast growth factor, bFGF = basic fibroblast growth factor, clinical trial, guideline, neuroprotection, neuroregeneration, spinal cord injury, stem cell

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          Abstract

          Acute traumatic spinal cord injury (SCI) is a devastating event with far-reaching physical, emotional, and economic consequences for patients, families, and society at large. Timely delivery of specialized care has reduced mortality; however, long-term neurological recovery continues to be limited. In recent years, a number of exciting neuroprotective and regenerative strategies have emerged and have come under active investigation in clinical trials, and several more are coming down the translational pipeline. Among ongoing trials are RISCIS (riluzole), INSPIRE (Neuro-Spinal Scaffold), MASC (minocycline), and SPRING (VX-210). Microstructural MRI techniques have improved our ability to image the injured spinal cord at high resolution. This innovation, combined with serum and cerebrospinal fluid (CSF) analysis, holds the promise of providing a quantitative biomarker readout of spinal cord neural tissue injury, which may improve prognostication and facilitate stratification of patients for enrollment into clinical trials. Given evidence of the effectiveness of early surgical decompression and growing recognition of the concept that "time is spine," infrastructural changes at a systems level are being implemented in many regions around the world to provide a streamlined process for transfer of patients with acute SCI to a specialized unit. With the continued aging of the population, central cord syndrome is soon expected to become the most common form of acute traumatic SCI; characterization of the pathophysiology, natural history, and optimal treatment of these injuries is hence a key public health priority. Collaborative international efforts have led to the development of clinical practice guidelines for traumatic SCI based on robust evaluation of current evidence. The current article provides an in-depth review of progress in SCI, covering the above areas.

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          Most cited references95

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          Incidence, prevalence and epidemiology of spinal cord injury: what learns a worldwide literature survey?

          Literature survey. To provide an overview of the literature data on incidence, prevalence and epidemiology of spinal cord injury (SCI) worldwide and to study their evolution since 1977. University Antwerp. The literature from 1995 onwards was searched on Pubmed. To include evolutionary data, we incorporated the results of three older studies. Two studies gave prevalence of SCI, and 17 incidence of SCI. The published data on prevalence of SCI was insufficient to consider the range of 223-755 per million inhabitants to be representative for a worldwide estimate. Reported incidence of SCI lies between 10.4 and 83 per million inhabitants per year. One-third of patients with SCI are reported to be tetraplegic and 50% of patients with SCI to have a complete lesion. The mean age of patients sustaining their injury at is reported as 33 years old, and the sex distribution (men/women) as 3.8/1. There is a need for improved registration of SCI, and publication of the findings in many parts of the world. This survey pleads for uniformity in methodology. The data show that the reported incidence and prevalence have not changed substantially over the past 30 years. Data from Northern America and Europe show higher figures for incidence, but prevalence figures have remained the same. Epidemiology of SCI seems to have changed during the last decades with a higher percentage of tetraplegia and of complete lesions. If such evolution is present worldwide, how it could eventually be prevented needs to be studied. Not applicable.
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            Proinflammatory cytokine synthesis in the injured mouse spinal cord: multiphasic expression pattern and identification of the cell types involved.

            We have studied the spatial and temporal distribution of six proinflammatory cytokines and identified their cellular source in a clinically relevant model of spinal cord injury (SCI). Our findings show that interleukin-1beta (IL-1beta) and tumor necrosis factor (TNF) are rapidly (<5 and 15 minutes, respectively) and transiently expressed in mice following contusion. At 30-45 minutes post SCI, IL-1beta and TNF-positive cells could already be seen over the entire spinal cord segment analyzed. Multilabeling analyses revealed that microglia and astrocytes were the two major sources of IL-1beta and TNF at these times, suggesting a role for these cytokines in gliosis. Results obtained from SCI mice previously transplanted with green fluorescent protein (GFP)-expressing hematopoietic stem cells confirmed that neural cells were responsible for the production of IL-1beta and TNF for time points preceding 3 hours. From 3 hours up to 24 hours, IL-1beta, TNF, IL-6, and leukemia inhibitory factor (LIF) were strongly upregulated within and immediately around the contused area. Colocalization studies revealed that all populations of central nervous system resident cells, including neurons, synthesized cytokines between 3 and 24 hours post SCI. However, work done with SCI-GFP chimeric mice revealed that at least some infiltrating leukocytes were responsible for cytokine production from 12 hours on. By 2 days post-SCI, mRNA signal for all the above cytokines had nearly disappeared. Notably, we also observed another wave of expression for IL-1beta and TNF at 14 days. Overall, these results indicate that following SCI, all classes of neural cells initially contribute to the organization of inflammation, whereas recruited immune cells mostly contribute to its maintenance at later time points. (c) 2006 Wiley-Liss, Inc.
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              Traumatic spinal cord injury in the United States, 1993-2012.

              Acute traumatic spinal cord injury results in disability and use of health care resources, yet data on contemporary national trends of traumatic spinal cord injury incidence and etiology are limited.
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                Author and article information

                Journal
                J Neurosurg Spine
                Journal of neurosurgery. Spine
                Journal of Neurosurgery Publishing Group (JNSPG)
                1547-5646
                1547-5646
                December 20 2018
                : 30
                : 1
                Affiliations
                [1 ] 1Division of Neurosurgery, Department of Surgery, and.
                [2 ] 2Institute of Medical Science, University of Toronto; and.
                [3 ] 3Department of Genetics and Development, Krembil Research Institute, University Health Network, Toronto, Ontario, Canada.
                Article
                2018.9.SPINE18682
                10.3171/2018.9.SPINE18682
                30611186
                9a9d95d9-4596-41d3-a468-cf1f4b85e2bd
                History

                FIM = Functional Independence Measure,Cmax = maximum concentration,CSPG = chondroitin sulfate proteoglycan,HGF = hepatocyte growth factor,MASC = Minocycline in Acute Spinal Cord Injury,MCP = monocyte chemotactic protein,aFGF = acidic fibroblast growth factor,neuroprotection,DTI = diffusion tensor imaging,CNS = central nervous system,spinal cord injury,CCS = central cord syndrome,TNF = tumor necrosis factor,IL = interleukin,OEC = olfactory ensheathing cell,MTR = MT ratio,MT = magnetization transfer,CELLTOP = Adipose Stem Cells for Traumatic Spinal Cord Injury,ASIA = American Spinal Injury Association,SCING = Spinal Cord Injury Neuroprotection with Glyburide,MSC = mesenchymal stem cell,IV = intravenous,CSF = cerebrospinal fluid,AUC = area under the curve,BSCB = blood–spinal cord barrier,Tmax = time to Cmax,MPSS = methylprednisolone sodium succinate,HAMC = hyaluronan/methylcellulose,GFAP = glial fibrillary acidic protein,stem cell,STASCIS = Surgical Timing in Acute Spinal Cord Injury Study,OPC = oligodendrocyte progenitor cell,ESC = embryonic stem cell,RISCIS = Riluzole in Acute Spinal Cord Injury Study,CST = corticospinal tract,bFGF = basic fibroblast growth factor,NSC = neural stem cell,GRASSP = Graded Redefined Assessment of Strength Sensibility and Prehension,neuroregeneration,clinical trial,G-CSF = granulocyte colony stimulating factor,AIS = ASIA Impairment Scale,guideline,RCT = randomized controlled trial,SCI = spinal cord injury,FES = functional electrical stimulation,SCIM = Spinal Cord Independence Measure
                FIM = Functional Independence Measure, Cmax = maximum concentration, CSPG = chondroitin sulfate proteoglycan, HGF = hepatocyte growth factor, MASC = Minocycline in Acute Spinal Cord Injury, MCP = monocyte chemotactic protein, aFGF = acidic fibroblast growth factor, neuroprotection, DTI = diffusion tensor imaging, CNS = central nervous system, spinal cord injury, CCS = central cord syndrome, TNF = tumor necrosis factor, IL = interleukin, OEC = olfactory ensheathing cell, MTR = MT ratio, MT = magnetization transfer, CELLTOP = Adipose Stem Cells for Traumatic Spinal Cord Injury, ASIA = American Spinal Injury Association, SCING = Spinal Cord Injury Neuroprotection with Glyburide, MSC = mesenchymal stem cell, IV = intravenous, CSF = cerebrospinal fluid, AUC = area under the curve, BSCB = blood–spinal cord barrier, Tmax = time to Cmax, MPSS = methylprednisolone sodium succinate, HAMC = hyaluronan/methylcellulose, GFAP = glial fibrillary acidic protein, stem cell, STASCIS = Surgical Timing in Acute Spinal Cord Injury Study, OPC = oligodendrocyte progenitor cell, ESC = embryonic stem cell, RISCIS = Riluzole in Acute Spinal Cord Injury Study, CST = corticospinal tract, bFGF = basic fibroblast growth factor, NSC = neural stem cell, GRASSP = Graded Redefined Assessment of Strength Sensibility and Prehension, neuroregeneration, clinical trial, G-CSF = granulocyte colony stimulating factor, AIS = ASIA Impairment Scale, guideline, RCT = randomized controlled trial, SCI = spinal cord injury, FES = functional electrical stimulation, SCIM = Spinal Cord Independence Measure

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