Spinal Cord Injury Immediately Changes the State of the Brain

Aguilar, Juan; Humanes-Valera, D.; Alonso-Calviño, Elena; Yagüe, Josué G.; Moxon, Karen A.; Oliviero, Antonio; Foffani, Guglielmo

doi:10.1523/jneurosci.0379-10.2010

Cited by 143 publications

(175 citation statements)

References 81 publications

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“…Our results show a spatial re-distribution of this eIF4E expression after SCI in the contra-lesional sensorimotor neocortices. In addition, these sensorimotor neocortices have slower spontaneous activity due to deafferentation [3]. Thus, our finding of eIF4E's re-distribution after SCI is consistent with a recent report that neuronal activation promotes redistribution of eIF4E in neurons [35].…”

Section: Discussionsupporting

confidence: 92%

“…An SCI may destroy few to almost all descending corticospinal (CS) and ascending sensory axons traveling through the site of the injury. As a result, CS axons are irreversibly injured and cortical activity dependent on sensory afferents is altered [1][2][3].…”

Section: Introductionmentioning

confidence: 99%

“…An SCI induces adaptive plastic reorganization of the primary sensorimotor neocortex, which indicates microcircuitry reorganizational events [3][4][5][6][7]. Electrophysiological studies show that SCI produces an immediate functional reorganization of the neocortex, while an increase in fMRI signal occurs by the 3rd day after an SCI [3,7].…”

Section: Introductionmentioning

confidence: 99%

“…Electrophysiological studies show that SCI produces an immediate functional reorganization of the neocortex, while an increase in fMRI signal occurs by the 3rd day after an SCI [3,7]. At the cellular level, dendritic spine morphology changes were found as early as 3 days post-SCI, and by 7 days post-SCI their number decreased [13].…”

Section: Introductionmentioning

confidence: 99%

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Acute adaptive responses of central sensorimotor neurons after spinal cord injury

Thompson

DiBona

Dubey

et al. 2010

Translational Neuroscience

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Spinal cord injury (SCI) can be a lifelong, devastating condition for both the patient and the caregiver, with a daunting incidence rate. Still, there are only limited available therapies and the effectiveness of precise regeneration within the central nervous system is minimal throughout postnatal life. Recently, improved regeneration after SCI was seen by manipulating a pathway in sensorimotor neocortices that is involved in phosphorylation of an RNA binding protein (RBP) required for mRNA translation, the Eukaryotic translation initiation factor 4E (eIF4E). Our data identifies rapid molecular alterations of eIF4E in the sensorimotor neocortices 1 and 3 days after a lateral hemisection SCI, used as a model for Brown-Séquard syndrome. The function of an RBP depends on both its distribution sites within the cell and its phosphorylation states. Indeed, we found both to be affected after SCI. There was a distinct subcellular redistribution of eIF4E and phosphorylated-eIF4E was reduced, indicating that the eIF4E's translation was disrupted. Upon identification and analysis of the mRNA cargo of eIF4E in uninjured sensorimotor neocortices, we found that eIF4E binds both Importin-13 (Ipo13) and Parvalbumin (Pv) mRNAs, indicating a role in their translation. Remarkably, eIF4E's interaction with both Ipo13 and Pv mRNAs was disrupted 1 and 3 days after SCI, despite preservation of total Ipo13 and Pv mRNA levels. Finally, we detected a selective loss of expression of both IPO13 and PV proteins in projection neurons of sensorimotor neocortices, as well as their disrupted dendritic polarity. Since IPO13 is predominantly expressed in neocortical projection neurons and PV in a subset of neocortical interneurons, these data suggest a strong acute effect of SCI on neocortical microcircuitry. Taken together, these data indicate that neocortical eIF4E and a subset of mRNAs may be rapidly recruited to translational machinery after SCI to promote adaptive regeneration response of sensorimotor neurons.

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Section: Discussionsupporting

confidence: 92%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Acute adaptive responses of central sensorimotor neurons after spinal cord injury

Thompson

DiBona

Dubey

et al. 2010

Translational Neuroscience

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“…No entanto, existe um método que tem sido pouco explorado nesta área, mas que pode trazer grandes benefícios, sendo ele a eletrofisiologia (Hebert et al, 2007;Aguilar et al, 2010;Gourab e Schmidt, 2010).…”

Section: Alterações Corticaisunclassified

Estratégia terapêutica após contusão da medula espinhal: recuperação funcional e estabilidade cortical sensório-motora

Miranda¹

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AGRADECIMENTOSAos meus pais, Renato e Aida, por me oferecerem sempre o melhor e terem me dado todas as condições de estudo. Sem o apoio deles, em todos os sentidos, este trabalho com certeza não teria sido realizado. Muito obrigada pelo carinho e amor.Ao meu namorado, Gustavo, pelo apoio, companheirismo, compreensão em relação ao tempo dedicado ao trabalho e amparo nos momentos difíceis.Aos meus irmãos, Renato, Vanessa e Paulo, com os quais eu aprendi a compartilhar, e a quem pude recorrer quando um problema surgisse. À Nice, minha segunda mãe, pelo carinho e atenção nas horas necessárias.A todos os meus familiares e amigos, pela convivência e apoio nas minhas decisões.Ao Edgard Morya, pela confiança em mim e no meu trabalho, além da paciência, empenho, dedicação e orientação criteriosa. À Angela Cristina do Valle, por ter me acompanhado desde o início desta trajetória e ter me guiado em relação aos caminhos a serem percorridos.

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Sensorimotor plasticity after spinal cord injury: a longitudinal and translational study

Jutzeler

Streijger

Aguilar

et al. 2018

Ann Clin Transl Neurol

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ObjectiveThe objective was to track and compare the progression of neuroplastic changes in a large animal model and humans with spinal cord injury.MethodsA total of 37 individuals with acute traumatic spinal cord injury were followed over time (1, 3, 6, and 12 months post‐injury) with repeated neurophysiological assessments. Somatosensory and motor evoked potentials were recorded in the upper extremities above the level of injury. In a reverse‐translational approach, similar neurophysiological techniques were examined in a porcine model of thoracic spinal cord injury. Twelve Yucatan mini‐pigs underwent a contusive spinal cord injury at T10 and tracked with somatosensory and motor evoked potentials assessments in the fore‐ and hind limbs pre‐ (baseline, post‐laminectomy) and post‐injury (10 min, 3 h, 12 weeks).ResultsIn both humans and pigs, the sensory responses in the cranial coordinates of upper extremities/forelimbs progressively increased from immediately post‐injury to later time points. Motor responses in the forelimbs increased immediately after experimental injury in pigs, remaining elevated at 12 weeks. In humans, motor evoked potentials were significantly higher at 1‐month (and remained so at 1 year) compared to normative values.ConclusionsDespite notable differences between experimental models and the human condition, the brain's response to spinal cord injury is remarkably similar between humans and pigs. Our findings further underscore the utility of this large animal model in translational spinal cord injury research.

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Spinal Cord Injury Immediately Changes the State of the Brain

Cited by 143 publications

References 81 publications

Acute adaptive responses of central sensorimotor neurons after spinal cord injury

Acute adaptive responses of central sensorimotor neurons after spinal cord injury

Estratégia terapêutica após contusão da medula espinhal: recuperação funcional e estabilidade cortical sensório-motora

Sensorimotor plasticity after spinal cord injury: a longitudinal and translational study

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