Neuronal Damage in Brain Inflammation

Aktaş, Orhan; Ullrich, Oliver; Infante-Duarte, Carmen; Nitsch, Robert; Zipp, Frauke

doi:10.1001/archneur.64.2.185

Cited by 199 publications

(120 citation statements)

References 30 publications

Supporting

Mentioning

112

Contrasting

Unclassified

Order By: Relevance

“…In aging, WMH represent the aftermath of longstanding WM injury that begins with changes in NAWM. 32 IL-6 influences inflammatory signaling leading to microglial sensitization 33,34 and neuronal damage, 35 which decreases the spatial restrictiveness within fibers, making them less anisotropic, 12 leading to a lower NAWM-FA signal on DTI. 12 Over time, cytokines increase bloodbrain permeability enabling reactive gliosis, 36 one of the pathologic hallmarks of WMH.…”

Section: Baseline Characteristics Valuesmentioning

confidence: 99%

Slow gait, white matter characteristics, and prior 10-year interleukin-6 levels in older adults

et al. 2016

View full text Add to dashboard Cite

Objective: To examine the relationship between gait speed and prior 10 years interleukin-6 (IL-6) burden in older adults. We then assessed whether white matter characteristics influence this relationship.Methods: In 179 community-dwelling older adults, gait speed was assessed on an automated walkway and serum IL-6 was assayed on ELISA. Concurrently, white matter characteristics were assessed on MRI by quantifying volume of white matter hyperintensities (WMH), a marker of small vessel disease, and normal-appearing white matter on fractional anisotropy (NAWM-FA), a marker of axonal integrity. IL-6 was assayed at regular intervals at gait assessment and over the prior 10 years and estimates of sustained 10-year IL-6 exposure and the rate of change in IL-6 over 10 years were obtained. Multivariate linear regressions were used to examine the relationships among sustained IL-6 exposure, rate of change in IL-6, gait speed, and white matter characteristics.Results: In this sample (age 83 years, 58% female, 41% black, gait speed 0.9 m/s), higher sustained IL-6 levels, but not the rate of change in IL-6 or IL-6 at gait assessment, was significantly related to slower gait (b 5 20.27, p , 0.001) and to higher WMH (b 5 0.23, p 5 0.002), but not NAWM-FA, withstanding covariate adjustments. WMH accounted for 30% attenuation in the relationship between higher sustained IL-6 levels and slower gait speed (p 5 0.043) in the mediation analyses.Conclusions: Sustained exposure to high IL-6 over 10 years rather than the rate of change in or an isolated high IL-6 level may adversely affect gait speed by influencing cerebral WMH. Increased levels of inflammatory cytokines such as interleukin-6 (IL-6) are cross-sectionally and longitudinally associated with poor physical function in older adults.1-5 IL-6 assayed at regular intervals over a long-term period may better capture sustained IL-6 exposure and rate of change rather than random assays spread apart over time. It is not known whether the sustained longterm exposure to IL-6 or rate of change in IL-6 contributes to the relationship between IL-6 and gait speed beyond a single concurrent indicator of inflammation.Higher IL-6 is linked to greater volume of white matter hyperintensities (WMH) on MRI in most studies [6][7][8] but not in all. 9 WMH are related to slow gait in older adults. 10,11 In regions that are free of WMH, which we refer to here as normal-appearing white matter (NAWM), subtle changes are detected on diffusion tensor imaging (DTI) as a reduction in fractional anisotropy of NAWM (NAWM-FA), denoting loss of myelin and astrogliosis at the microstructural level.

show abstract

Section: Baseline Characteristics Valuesmentioning

confidence: 99%

Slow gait, white matter characteristics, and prior 10-year interleukin-6 levels in older adults

et al. 2016

View full text Add to dashboard Cite

show abstract

“…The close link that has been demonstrated to occur between inflammation and neurodegeneration in the pathogenesis of this heterogeneous group of neurological diseases led to the hypothesis that immune mechanisms may control and even promote neuronal degeneration and that common immunological pathways may result in neurotoxicity and subsequent neuronal death both in inflammatory and non-inflammatory CNS diseases [12,13]. For the same reasons the classical dichotomy between inflammatory and degenerative diseases of the CNS has recently been challenged and it is now believed that different neurological diseases probably share the molecular and synaptic mechanisms leading to symptoms progression and disability.…”

Section: DI Filippo Et Al / Mitochondria and Neuroinflammationmentioning

confidence: 99%

Mitochondria and the Link Between Neuroinflammation and Neurodegeneration

Filippo

Chiasserini

Tozzi

et al. 2010

JAD

128

100

View full text Add to dashboard Cite

Abstract. The innate immune response is thought to exert a dichotomous role in the brain. Indeed, although molecules of the innate immune response can promote repair mechanisms, during neuroinflammatory processes many harmful mediators are also released. Signs of neuroinflammation and neurodegeneration represent a ubiquitous pathological finding during the course of several different neurological diseases. Interestingly, it has been proposed that mitochondria may exert a crucial role in the pathogenesis of both inflammatory and neurodegenerative central nervous system disorders. In this review, we describe the mechanisms by which neuroinflammation and mitochondrial impairment may synergistically trigger a vicious cycle ultimately leading to neuronal death. In particular, we describe the close relationship existing among neuroinflammation, neurodegeneration, and mitochondrial impairment in three different widely-diffused neurological diseases in which these pathogenetic events coexist, namely multiple sclerosis, Parkinson's disease, and Alzheimer's disease.

show abstract

“…Soon after the CNS is invaded by virus, two hypothetical mechanisms are believed to activate which are, neuronal retrograde dissemination and hematogenous dissemination, through which pathogen reach the brain by traversing the BBB [42,43]. Virus can replicate in macrophage and CC chemokine receptor 5 (CCR5+) T cells Review Amarendranath Choudhury in the CNS region during developmental stages and assists in the progression of dementia [44].…”

Section: Infectionsmentioning

confidence: 99%

Effect and Disease Indicative Role of Inflammation in Neurodegenerative Pathology: A Mechanistic Crosstalk of Promise and Dilemma

Choudhury¹,

Chakraborty²,

Banerjee³

et al. 2018

Neuropsychiatry

View full text Add to dashboard Cite

The pathobiology of neuronal cell loss due to various endogenous or exogenous influences is clinically termed as neurodegeneration. Neurodegeneration has been reported to be the major contributor to aging and central nervous system diseases. Apart from aging and endogenous involvement, neurodegeneration also has been reported from viral infection and prion diseases. Studies have shown that, chronic degeneration of neuronal cells initiate the pathology of Alzheimer's disease-the most prevalent neurodegenerative disorder in the world. Similar neurodegenerative pathology is also evident in Parkinson's disease, multiple sclerosis, and Amyotrophic Lateral Sclerosis. Neurodegeneration negatively affects the mental and physical functioning of the patient. Intriguingly, the involvement of inflammation has been linked as the most crucial entity in the mechanistic progress of neurodegeneration. Moreover, recent data also have shown that inflammatory biomarkers can prognosticate the silent progress of neurodegeneration through low-cost diagnostic approach. Mainly, Th17 and MDSCs are the particular immune cells, which have been reported to assist adequately to get a detailed insight into the underlying pathological process in neurodegeneration. Similarly, depression and dementia are also having a crucial association with pro-inflammatory cytokines, which in chronic spectrum indicates the degenerative pathology. Together, available literatures are depicting a direct association between neuroinflammation and neurodegeneration. In the present review, we have summed up all the neuropathologies in light of inflammation and emphasized the possible diagnostic measures by using inflammatory cells and mediators as biomarkers for neurodegenerative diseases.

show abstract

Neuronal Damage in Brain Inflammation

Cited by 199 publications

References 30 publications

Slow gait, white matter characteristics, and prior 10-year interleukin-6 levels in older adults

Slow gait, white matter characteristics, and prior 10-year interleukin-6 levels in older adults

Mitochondria and the Link Between Neuroinflammation and Neurodegeneration

Effect and Disease Indicative Role of Inflammation in Neurodegenerative Pathology: A Mechanistic Crosstalk of Promise and Dilemma

Contact Info

Product

Resources

About