Activity-triggered tetrapartite neuron–glial interactions following peripheral injury

Ren, Ke; Dubner, Ronald

doi:10.1016/j.coph.2015.09.006

Cited by 40 publications

(42 citation statements)

References 94 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…For instance, immunocompetent CNS cells can detect pathologically enhanced afferent neuronal activity occurring after peripheral injury. In this case, neuroinflammation is termed ‘neurogenic’ 5, 6 . Just like classical neuroinflammation, neurogenic neuroinflammation can be adaptive.…”

Section: Introductionmentioning

confidence: 99%

In Vivo Imaging of Human Neuroinflammation

Albrecht¹,

Granziera

Hooker³

et al. 2016

ACS Chem. Neurosci.

175

146

View full text Add to dashboard Cite

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.

show abstract

Section: Introductionmentioning

confidence: 99%

In Vivo Imaging of Human Neuroinflammation

Albrecht¹,

Granziera

Hooker³

et al. 2016

ACS Chem. Neurosci.

175

146

View full text Add to dashboard Cite

show abstract

“…The effects of inflammation on nociception have been extensively studied (reviewed in Ren and Dubner, 2015; Stemkowski and Smith, 2012; Woolf and Salter, 2000) and provide a framework to reference respiration related studies. Both systemic and local inflammation can induce peripheral and central neural sensitization leading to hyperalgesia and allodynia (Luo et al, 2014).…”

Section: Cns Inflammation and Neuroplasticitymentioning

confidence: 99%

“…Briefly, peripheral injury and inflammation sensitizes primary nociceptive neurons via inflammatory mediators including bradykinin and prostaglandins (reviewed in Pethő and Reeh, 2012). Peripheral sensitization and increased spontaneous activity of nociceptive neurons cause activity-dependent changes in the spinal dorsal horn second order neurons (Woolf and Salter, 2000), an effect mediated by multiple cell types including microglia, astrocytes, and neurons (Ren and Dubner, 2015). Microglia in the dorsal horn respond rapidly to increased primary afferent activity by increasing in number and changing morphology (McMahon and Malcangio, 2009).…”

Section: Cns Inflammation and Neuroplasticitymentioning

confidence: 99%

The impact of inflammation on respiratory plasticity

Hocker

Stokes

Powell

et al. 2017

Experimental Neurology

View full text Add to dashboard Cite

Breathing is a vital homeostatic behavior and must be precisely regulated throughout life. Clinical conditions commonly associated with inflammation, undermine respiratory function may involve plasticity in respiratory control circuits to compensate and maintain adequate ventilation. Alternatively, other clinical conditions may evoke maladaptive plasticity. Yet, we have only recently begun to understand the effects of inflammation on respiratory plasticity. Here we review some of common models used to investigate the effects of inflammation and discuss the impact of inflammation on nociception, chemosensory plasticity, medullary respiratory centers, motor plasticity in motor neurons and respiratory frequency, and adaptation to high altitude. We provide new data suggesting glial cells contribute to CNS inflammatory gene expression after 24 hours of sustained hypoxia and inflammation induced by 8 hours of intermittent hypoxia inhibits long-term facilitation of respiratory frequency. We also discuss how inflammation can have opposite effects on the capacity for plasticity, whereby it is necessary for increases in the hypoxic ventilatory response with sustained hypoxia but inhibits phrenic long term facilitation after intermittent hypoxia. This review highlights gaps in our knowledge about the effects of inflammation on respiratory control (development, age, and sex differences). In summary, data to date suggest plasticity can be either adaptive or maladaptive and understanding how inflammation alters the respiratory system is crucial for development of better therapeutic interventions to promote breathing and for utilization of plasticity as a clinical treatment.

show abstract

“…Activation and proliferation of microglia and astrocytes, and subsequent over-production of inflammatory mediators such as TNF-α, IL-1β and MCP-1 are causative factors causing excessive activation of spinal dorsal horn neurons (Grace, Hutchinson, Maier, & Watkins, 2014; Ren & Dubner, 2016). In this context, TNF-α, IL-1β (Kawasaki, Zhang, Cheng, & Ji, 2008; Yan & Weng, 2013) and MCP-1 (Gao et al, 2009) enhance excitatory glutamatergic synaptic activities in the spinal dorsal horn while inhibitory GABAergic synaptic activities in the same region are suppressed by TNF-α, IL-1β (Kawasaki et al, 2008; Yan, Jiang, & Weng, 2015).…”

Section: Introductionmentioning

confidence: 99%

EZH2 regulates spinal neuroinflammation in rats with neuropathic pain

Yadav

Weng

2017

Neuroscience

View full text Add to dashboard Cite

Alteration in gene expression along the pain signaling pathway is a key mechanism contributing to the genesis of neuropathic pain. Accumulating studies have shown that epigenetic regulation plays a crucial role in nociceptive process in the spinal dorsal horn. In this present study, we investigated the role of enhancer of zeste homolog-2 (EZH2), a subunit of the polycomb repressive complex 2, in the spinal dorsal horn in the genesis of neuropathic pain in rats induced by partial sciatic nerve ligation. EZH2 is a histone methyltransferase, which catalyzes the methylation of histone H3 on K27 (H3K27), resulting in gene silencing. We found that levels of EZH2 and tri-methylated H3K27 (H3K27TM) in the spinal dorsal horn were increased in rats with neuropathic pain on day 3 and day 10 post nerve injuries. EZH2 was predominantly expressed in neurons in the spinal dorsal horn under normal conditions. The number of neurons with EZH2 expression was increased after nerve injury. More strikingly, nerve injury drastically increased the number of microglia with EZH2 expression by more than 7 fold. Intrathecal injection of the EZH2 inhibitor attenuated the development and maintenance of mechanical and thermal hyperalgesia in rats with nerve injury. Such analgesic effects were concurrently associated with the reduced levels of EZH2, H3K27TM, Iba1, GFAP, TNF-α, IL-1β, and MCP-1 in the spinal dorsal horn in rats with nerve injury. Our results highly suggest that targeting the EZH2 signaling pathway could be an effective approach for the management of neuropathic pain.

show abstract

Activity-triggered tetrapartite neuron–glial interactions following peripheral injury

Cited by 40 publications

References 94 publications

In Vivo Imaging of Human Neuroinflammation

In Vivo Imaging of Human Neuroinflammation

The impact of inflammation on respiratory plasticity

EZH2 regulates spinal neuroinflammation in rats with neuropathic pain

Contact Info

Product

Resources

About