Immune Surveillance of the CNS following Infection and Injury

Russo, Matthew V.; McGavern, Dorian B.

doi:10.1016/j.it.2015.08.002

Cited by 158 publications

(136 citation statements)

References 106 publications

(144 reference statements)

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“…glial activation is a factor in all three neuropathologies). The aim of this review is not to provide an exhaustive description of every neuroinflammatory element, which has been discussed extensively 2, 6, 13 . Rather, we will focus on methods to image in vivo biological mechanisms that are generally recognized as major players of neuroinflammation in human CNS disorders.…”

Section: Introductionmentioning

confidence: 99%

In Vivo Imaging of Human Neuroinflammation

Albrecht¹,

Granziera

Hooker³

et al. 2016

ACS Chem. Neurosci.

172

146

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Neuroinflammation is implicated in the pathophysiology of a growing number of human disorders, including multiple sclerosis, chronic pain, traumatic brain injury, and amyotrophic lateral sclerosis. As a result, interest in the development of novel methods to investigate neuroinflammatory processes, for the purpose of diagnosis, development of new therapies, and treatment monitoring, has surged over the past 15 years. Neuroimaging offers a wide array of non- or minimally invasive techniques to characterize neuroinflammatory processes. The intent of this Review is to provide brief descriptions of currently available neuroimaging methods to image neuroinflammation in the human central nervous system (CNS) in vivo. Specifically, because of the relatively widespread accessibility of equipment for nuclear imaging (positron emission tomography [PET]; single photon emission computed tomography [SPECT]) and magnetic resonance imaging (MRI), we will focus on strategies utilizing these technologies. We first provide a working definition of “neuroinflammation” and then discuss available neuroimaging methods to study human neuroinflammatory processes. Specifically, we will focus on neuroimaging methods that target (1) the activation of CNS immunocompetent cells (e.g. imaging of glial activation with TSPO tracer [11C]PBR28), (2) compromised BBB (e.g. identification of MS lesions with gadolinium-enhanced MRI), (3) CNS-infiltration of circulating immune cells (e.g. tracking monocyte infiltration into brain parenchyma with iron oxide nanoparticles and MRI), and (4) pathological consequences of neuroinflammation (e.g. imaging apoptosis with [99mTc]Annexin V or iron accumulation with T2* relaxometry). This Review provides an overview of state-of-the-art techniques for imaging human neuroinflammation which have potential to impact patient care in the foreseeable future.

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Section: Introductionmentioning

confidence: 99%

In Vivo Imaging of Human Neuroinflammation

Albrecht¹,

Granziera

Hooker³

et al. 2016

ACS Chem. Neurosci.

172

146

View full text Add to dashboard Cite

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“…This time point coincides with the recruitment of other peripheral immune cells and the local activation of microglia and astrocytes. CCR2-expressing monocytes are the major immune cell population that infiltrates into the damaged tissue at days 3–5 post-injury, although T cells, natural killer (NK) cells, and dendritic cells (DCs) can also be detected around the injury site (15, 28–30). The coordinated production of chemokines following trauma orchestrates the recruitment of immune cells to areas of brain injury.…”

Section: The Kinetics Of the Immune Response To Brain Injurymentioning

confidence: 99%

Emerging Roles for the Immune System in Traumatic Brain Injury

2016

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Traumatic brain injury (TBI) affects an ever-growing population of all ages with long-term consequences on health and cognition. Many of the issues that TBI patients face are thought to be mediated by the immune system. Primary brain damage that occurs at the time of injury can be exacerbated and prolonged for months or even years by chronic inflammatory processes, which can ultimately lead to secondary cell death, neurodegeneration, and long-lasting neurological impairment. Researchers have turned to rodent models of TBI in order to understand how inflammatory cells and immunological signaling regulate the post-injury response and recovery mechanisms. In addition, the development of numerous methods to manipulate genes involved in inflammation has recently expanded the possibilities of investigating the immune response in TBI models. As results from these studies accumulate, scientists have started to link cells and signaling pathways to pro- and anti-inflammatory processes that may contribute beneficial or detrimental effects to the injured brain. Moreover, emerging data suggest that targeting aspects of the immune response may offer promising strategies to treat TBI. This review will cover insights gained from studies that approach TBI research from an immunological perspective and will summarize our current understanding of the involvement of specific immune cell types and cytokines in TBI pathogenesis.

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“…ATP also is released at low concentrations into the extracellular space as a mechanism of inter-cellular signaling under physiological conditions. In contrast, the passive, extracellular release of high concentrations of ATP initiates innate immune activation following traumatic or ischemic injuries [51]. ATP, a microglial chemoattractant that is rapidly released into the extracellular space from damaged neurons, is associated with poor outcomes after TBI [52, 53], yet the mechanistic and functional significance remains largely undefined.…”

Section: Damage Associated Molecular Patterns (Damps): Mediators Omentioning

confidence: 99%

White matter damage after traumatic brain injury: A role for damage associated molecular patterns

Braun

Vaibhav

Saad

et al. 2017

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Diseas

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Traumatic brain injury (TBI) is a leading cause of mortality and long-term morbidity worldwide. Despite decades of pre-clinical investigation, therapeutic strategies focused on acute neuroprotection failed to improve TBI outcomes. This lack of translational success has necessitated a reassessment of the optimal targets for intervention, including a heightened focus on secondary injury mechanisms. Chronic immune activation correlates with progressive neurodegeneration for decades after TBI; however, significant challenges remain in functionally and mechanistically defining immune activation after TBI. In this review, we explore the burgeoning evidence implicating the acute release of damage associated molecular patterns (DAMPs), such as adenosine 5′-triphosphate (ATP), high mobility group box protein 1 (HMGB1), S100 proteins, and hyaluronic acid in the initiation of progressive neurological injury, including white matter loss after TBI. The role that pattern recognition receptors, including toll-like receptor and purinergic receptors, play in progressive neurological injury after TBI is detailed. Finally, we provide support for the notion that resident and infiltrating macrophages are critical cellular targets linking acute DAMP release with adaptive immune responses and chronic injury after TBI. The therapeutic potential of targeting DAMPs and barriers to clinical translational, in the context of TBI patient management, are discussed.

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Immune Surveillance of the CNS following Infection and Injury

Cited by 158 publications

References 106 publications

In Vivo Imaging of Human Neuroinflammation

In Vivo Imaging of Human Neuroinflammation

Emerging Roles for the Immune System in Traumatic Brain Injury

White matter damage after traumatic brain injury: A role for damage associated molecular patterns

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