Newly Formed Endothelial Cells Regulate Myeloid Cell Activity Following Spinal Cord Injury via Expression of CD200 Ligand

Cohen, Michal; Ben-Yehuda, Hila; Porat, Ziv; Rapôso, Catarina; Gordon, Siamon; Schwartz, Michal

doi:10.1523/jneurosci.2199-16.2016

Cited by 24 publications

(11 citation statements)

References 82 publications

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“…We found these meningeal TLS-like ectopic structures during the late phase of response to acute injury, when apparently moderate levels of unresolved inflammation persist within the spinal cord parenchyma ( Shechter et al, 2009 ; Cohen et al, 2014 , 2017 ; Raposo et al, 2014 ). These meningeal structures were observed in close proximity to the site of insult within the parenchyma, harboring cells with immunological properties that differed from the lymphocytes found in the spinal cord parenchyma or in the cLN.…”

Section: Discussionmentioning

confidence: 75%

“…Following any deviation from homeostasis in the central nervous system (CNS), the immune response is activated to facilitate repair and to resolve the detrimental parenchymal inflammation. Despite the privileged nature of the CNS, many immunological process take place within its boundaries, both in homeostasis and under pathological conditions, with similarities to those that occur in the periphery ( Lalancette-Hebert et al, 2007 ; Liesz et al, 2009 ; Shechter et al, 2009 ; David & Kroner, 2011 ; London et al, 2011, 2013 ; Martino et al, 2011 ; Michaud et al, 2013 ; Cohen et al, 2014, 2017 ; Peruzzotti-Jametti et al, 2014 ; Raposo et al, 2014 ; Kunis et al, 2015 ; Russo & McGavern, 2015 ).…”

Section: Introductionmentioning

confidence: 99%

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Meningeal lymphoid structures are activated under acute and chronic spinal cord pathologies

et al. 2020

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Tertiary lymphoid structures (TLS) are organized aggregates of B and T cells formed ectopically during different stages of life in response to inflammation, infection, or cancer. Here, we describe formation of structures reminiscent of TLS in the spinal cord meninges under several central nervous system (CNS) pathologies. After acute spinal cord injury, B and T lymphocytes locally aggregate within the meninges to form TLS-like structures, and continue to accumulate during the late phase of the response to the injury, with a negative impact on subsequent pathological conditions, such as experimental autoimmune encephalomyelitis. Using a chronic model of spinal cord pathology, the mSOD1 mouse model of amyotrophic lateral sclerosis, we further showed by single-cell RNA-sequencing that a meningeal lymphocyte niche forms, with a unique organization and activation state, including accumulation of pre-B cells in the spinal cord meninges. Such a response was not found in the CNS-draining cervical lymph nodes. The present findings suggest that a special immune response develops in the meninges during various neurological pathologies in the CNS, a possible reflection of its immune privileged nature.

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Section: Discussionmentioning

confidence: 75%

Section: Introductionmentioning

confidence: 99%

Meningeal lymphoid structures are activated under acute and chronic spinal cord pathologies

et al. 2020

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“…Endothelial cells from injured blood vessels were slow to reform blood vessels and were rarely invading the lesion site. In contrast, in mammals endothelial cells accumulate in the injury site, where they may have anti-inflammatory functions 51 . Myelinating cells bridged the lesion site, but were not abundant and only did so, when axons had already crossed the lesion site.…”

Section: Discussionmentioning

confidence: 99%

Dynamic control of proinflammatory cytokines Il-1β and Tnf-α by macrophages in zebrafish spinal cord regeneration

et al. 2018

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Spinal cord injury leads to a massive response of innate immune cells in non-regenerating mammals, but also in successfully regenerating zebrafish. However, the role of the immune response in successful regeneration is poorly defined. Here we show that inhibiting inflammation reduces and promoting it accelerates axonal regeneration in spinal-lesioned zebrafish larvae. Mutant analyses show that peripheral macrophages, but not neutrophils or microglia, are necessary for repair. Macrophage-less irf8 mutants show prolonged inflammation with elevated levels of Tnf-α and Il-1β. Inhibiting Tnf-α does not rescue axonal growth in irf8 mutants, but impairs it in wildtype animals, indicating a pro-regenerative role of Tnf-α. In contrast, decreasing Il-1β levels or number of Il-1β+ neutrophils rescue functional regeneration in irf8 mutants. However, during early regeneration, interference with Il-1β function impairs regeneration in irf8 and wildtype animals. Hence, inflammation is dynamically controlled by macrophages to promote functional spinal cord regeneration in zebrafish.

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“…This effect was further shown to rely on BDNF/TrkB signaling [ 47 ], as well as inhibition of matrix metalloproteinases (MMPs) [ 173 ], which restructure extracellular matrices and damage the blood–spinal-cord barrier after SCI [ 174 , 175 ]. Interestingly, another study found that after SCI, proliferating endothelial cells located in the core of the lesion upregulate CD200, which hinders inflammation [ 176 ], while yet another study found that treadmill exercise upregulates both CD200 and its receptor after stroke in rats [ 177 ]. Thus, it is possible that the decrease in inflammatory signaling observed with exercise occurs in part by increasing the endothelial release of CD200 and increasing the expression of the CD200 receptor.…”

Section: Other Considerationsmentioning

confidence: 99%

Exercise-Induced Plasticity in Signaling Pathways Involved in Motor Recovery after Spinal Cord Injury

Bilchak

Caron

Côté

2021

IJMS

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Spinal cord injury (SCI) leads to numerous chronic and debilitating functional deficits that greatly affect quality of life. While many pharmacological interventions have been explored, the current unsurpassed therapy for most SCI sequalae is exercise. Exercise has an expansive influence on peripheral health and function, and by activating the relevant neural pathways, exercise also ameliorates numerous disorders of the central nervous system (CNS). While the exact mechanisms by which this occurs are still being delineated, major strides have been made in the past decade to understand the molecular underpinnings of this essential treatment. Exercise rapidly and prominently affects dendritic sprouting, synaptic connections, neurotransmitter production and regulation, and ionic homeostasis, with recent literature implicating an exercise-induced increase in neurotrophins as the cornerstone that binds many of these effects together. The field encompasses vast complexity, and as the data accumulate, disentangling these molecular pathways and how they interact will facilitate the optimization of intervention strategies and improve quality of life for individuals affected by SCI. This review describes the known molecular effects of exercise and how they alter the CNS to pacify the injury environment, increase neuronal survival and regeneration, restore normal neural excitability, create new functional circuits, and ultimately improve motor function following SCI.

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Newly Formed Endothelial Cells Regulate Myeloid Cell Activity Following Spinal Cord Injury via Expression of CD200 Ligand

Cited by 24 publications

References 82 publications

Meningeal lymphoid structures are activated under acute and chronic spinal cord pathologies

Meningeal lymphoid structures are activated under acute and chronic spinal cord pathologies

Dynamic control of proinflammatory cytokines Il-1β and Tnf-α by macrophages in zebrafish spinal cord regeneration

Exercise-Induced Plasticity in Signaling Pathways Involved in Motor Recovery after Spinal Cord Injury

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