NO mediates microglial response to acute spinal cord injury under ATP control <i>in vivo</i>

Dibaj, Payam; Nadrigny, Fabien; Steffens, Heinz; Scheller, Anja; Hirrlinger, Johannes; Schomburg, E. D.; Neusch, Clemens; Kirchhoff, Frank

doi:10.1002/glia.20993

Cited by 128 publications

(130 citation statements)

References 36 publications

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“…Moreover, activated microglia may migrate from to site of injury and move along degenerating and intact axons and initiate an inflammatory response in regions far from the site of impact (68). Regardless of the mechanism responsible for the widespread pathophysiological alterations observed, our study corroborates the notion that controlled cortical impact is actually more than a focal brain injury ( 100; 296).…”

Section: B2supporting

confidence: 81%

Pathological and Pathophysiological Alterations in Temporal Lobe Structures After Mild Traumatic Brain Injury

Almeida¹,

Camila²

2014

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Section: B2supporting

confidence: 81%

Pathological and Pathophysiological Alterations in Temporal Lobe Structures After Mild Traumatic Brain Injury

Almeida¹,

Camila²

2014

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“…6 J-L). Since in our previous study we detected an extremely low number of infiltrated leukocytes in BCCAo model [27], these cells are likely to be migrating microglia [30,31]. Counting of these CD45…”

Section: Nfkb1 Deficiency Strongly Reduced Bccao-induced Microgliosismentioning

confidence: 93%

Deletion of Nuclear Factor kappa B p50 Subunit Decreases Inflammatory Response and Mildly Protects Neurons from Transient Forebrain Ischemia-induced Damage

et al. 2016

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Transient forebrain ischemia induces delayed death of the hippocampal pyramidal neurons, particularly in the CA2 and medial CA1 area. Early pharmacological inhibition of inflammatory response can ameliorate neuronal death, but it also inhibits processes leading to tissue regeneration. Therefore, research efforts are now directed to modulation of post-ischemic inflammation, with the aim to promote beneficial effects of inflammation and limit adverse effects. Transcription factor NF-κB plays a key role in the inflammation and cell survival/apoptosis pathways. In the brain, NF-κB is predominantly found in the form of a heterodimer of p65 (RelA) and p50 subunit, where p65 has a transactivation domain while p50 is chiefly involved in DNA binding. In this study, we subjected middle-aged Nfkb1 knockout mice (lacking p50 subunit) and wild-type controls of both sexs to 17 min of transient forebrain ischemia and assessed mouse performance in a panel of behavioral tests after two weeks of post-operative recovery. We found that ischemia failed to induce clear memory and motor deficits, but affected spontaneous locomotion in genotype-and sex-specific way. We also show that both the lack of the NF-κB p50 subunit and female sex independently protected CA2 hippocampal neurons from ischemia-induced cell death. Additionally, the NF-κB p50 subunit deficiency significantly reduced ischemia-induced microgliosis, astrogliosis, and neurogenesis. Lower levels of hippocampal microgliosis significantly correlated with faster spatial learning. We conclude that NF-κB regulates the outcome of transient forebrain ischemia in middle-aged subjects in a sex-specific way, having an impact not only on neuronal death but also specific inflammatory responses and neurogenesis.

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“…Microglia are among the first myeloid cells to be set in motion, responding to changes in extracellular ions and ATP within minutes to hours post-injury [6][7][8].…”

Section: Myeloid Cells In Inflammationmentioning

confidence: 99%

Emerging Concepts in Myeloid Cell Biology after Spinal Cord Injury

Hawthorne

Popovich

2011

Neurotherapeutics

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Summary: Traumatic spinal cord injury (SCI) affects the activation, migration, and function of microglia, neutrophils and monocyte/macrophages. Because these myeloid cells can positively and negatively affect survival of neurons and glia, they are among the most commonly studied immune cells. However, the mechanisms that regulate myeloid cell activation and recruitment after SCI have not been adequately defined. In general, the dynamics and composition of myeloid cell recruitment to the injured spinal cord are consistent between mammalian species; only the onset, duration, and magnitude of the response vary. Emerging data, mostly from rat and mouse SCI models, indicate that resident and recruited myeloid cells are derived from multiple sources, including the yolk sac during development and the bone marrow and spleen in adulthood. After SCI, a complex array of chemokines and cytokines regulate myelopoiesis and intraspinal trafficking of myeloid cells. As these cells accumulate in the injured spinal cord, the collective actions of diverse cues in the lesion environment help to create an inflammatory response marked by tremendous phenotypic and functional heterogeneity. Indeed, it is difficult to attribute specific reparative or injurious functions to one or more myeloid cells because of convergence of cell function and difficulties in using specific molecular markers to distinguish between subsets of myeloid cell populations. Here we review each of these concepts and include a discussion of future challenges that will need to be overcome to develop newer and improved immune modulatory therapies for the injured brain or spinal cord.

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NO mediates microglial response to acute spinal cord injury under ATP control in vivo

Cited by 128 publications

References 36 publications

Pathological and Pathophysiological Alterations in Temporal Lobe Structures After Mild Traumatic Brain Injury

Pathological and Pathophysiological Alterations in Temporal Lobe Structures After Mild Traumatic Brain Injury

Deletion of Nuclear Factor kappa B p50 Subunit Decreases Inflammatory Response and Mildly Protects Neurons from Transient Forebrain Ischemia-induced Damage

Emerging Concepts in Myeloid Cell Biology after Spinal Cord Injury

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