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Biomarkers in Spinal Cord Injury: from Prognosis to Treatment

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Abstract

Spinal cord injury (SCI) is considered an incurable condition, having a heterogenous recovery and uncertain prognosis. Therefore, a reliable prediction of the improvement in the acute phase could benefit patients. Physicians are unanimous in insisting that at the initial damage of the spinal cord (SC), the patient should be carefully evaluated in order to help selecting an appropriate neuroprotective treatment. However, currently, neurologic impairment after SCI is measured and classified by functional examination. The identification of prognostic biomarkers of SCI would help to designate SC injured patients and correlate to diagnosis and correct treatment. Some proteins have already been identified as good potential biomarkers of central nervous system injury, both in cerebrospinal fluid (CSF) and blood serum. However, the problem for using them as biomarkers is the way they should be collected, as acquiring CSF through a lumbar puncture is significantly invasive. Remarkably, microRNAs (miRNAs) have emerged as interesting biomarker candidates because of their stability in biological fluids and their tissue specificity. Several miRNAs have been identified to have their expressions altered in SCI in many animal models, making them promising candidates as biomarkers after SCI. Moreover, there are yet no effective therapies for SCI. It is already known that altered lysophospholipids (LPs) signaling are involved in the biology of disorders, such as inflammation. Reports have demonstrated that LPs when locally distributed can regulate SCI repair and key secondary injury processes such as apoptosis and inflammation, and so could become in the future new therapeutic approaches for treating SCI.

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Abbreviations

ASIA:

American Spinal Injuries Association

BSCB:

blood-spinal cord barrier

BMPs:

bone morphogenetic proteins

BDNF:

brain-derived neurotrophic factor

S100β:

calcium-binding protein S100-beta

CNS:

central nervous system

CSF:

cerebrospinal fluid

COX2:

cyclooxygenase 2

FGF-β:

fibroblast growth factor beta 1

GPCRs:

G protein–coupled receptors

GDNF:

glial cell-derived neurotrophic factor

GFAP:

glial fibrillary acidic protein

IFNγ:

interferon gamma

IGF (I and II):

insulin-like growth factor I and II

IL (1β; 1α and 6):

interleukin-1β; 1α and 6

IL-4R and IL-2Rα:

interleukin receptors

ISNCSCI:

International Standards for Neurological Classification of Spinal Cord Injury

JAK:

Janus-activated kinase

LPA:

Lysophosphatidic acid

LPs:

lysophospholipids

MRI:

magnetic resonance imaging

mTOR:

mechanistic target of rapamycin

miRNA:

microRNA

MAP-2:

microtubule-associated protein 2

MOG:

myelin-oligodendrocyte glycoprotein

NFL and NFH:

neurofilament proteins (light and heavy)

NF-κB:

factor kappa B

PTEN:

phosphatase and tensin homolog

PDGF:

platelet-derive growth factor

S1P:

Sphingosine-1 phosphate

SBDPs:

αII-spectrin breakdown products

SC:

spinal cord

SCI:

spinal cord injury

STAT:

signal transducer and activation of transcription family

SOCS-3:

suppressor of cytokine signaling 3

TGF-β:

transforming growth factor-β

TNF-α:

tumor necrosis factor-α

VEGF:

vascular endothelial growth factor

VGF:

inducible nerve growth factor

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Acknowledgments

This work was supported by the National Institute for Translational Neuroscience (INNT) of the Ministry of Science and Technology; Brazilian Federal Agency for the Support and Evaluation of Graduate Education (CAPES) of the Ministry of Education; National Council for Scientific and Technological Development (CNPq); Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro Carlos Chagas Filho Research Support Foundation (FAPERJ); Ary Frauzino Foundation for Cancer Research and Pró-Saúde Associação Beneficiente de Assistência Social e Hospitalar.

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  1. CCS, Universidade Federal do Rio de Janeiro, Av. Carlos Chagas Filho 373 - Cidade Universitária - Bloco F, Sala F24, Rio de Janeiro, Brazil

    Leonardo Fonseca Rodrigues & Vivaldo Moura-Neto

  2. Hospital São Vicente de Paulo, Rua Gonçalves Crespo, 430 Tijuca, Rio de Janeiro, RJ, Brazil

    Leonardo Fonseca Rodrigues

  3. Instituto Estadual do Cérebro Paulo Niemeyer, Rua do Rezende 156, Rio de Janeiro, RJ, Brazil

    Vivaldo Moura-Neto & Tania Cristina Leite de Sampaio e Spohr

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  1. Leonardo Fonseca Rodrigues
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Correspondence to Tania Cristina Leite de Sampaio e Spohr.

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Rodrigues, L.F., Moura-Neto, V. & e Spohr, T.C.L. Biomarkers in Spinal Cord Injury: from Prognosis to Treatment. Mol Neurobiol 55, 6436–6448 (2018). https://doi.org/10.1007/s12035-017-0858-y

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