Neuroinflammatory component of gray matter pathology in multiple sclerosis

Herranz, Elena; Giannì, Costanza; Louapre, Céline; Treabă, Constantina Andrada; Govindarajan, Sindhuja T.; Ouellette, Russell; Loggia, Marco L.; Sloane, Jacob A.; Madigan, Nancy; Izquierdo‐Garcia, David; Ward, Noreen; Mangeat, Gabriel; Granberg, Tobias; Klawiter, Eric C.; Catana, Ciprian; Hooker, Jacob M.; Taylor, Norman E.; Ionete, Carolina; Kinkel, Revere P.; Mainero, Caterina

doi:10.1002/ana.24791

Cited by 173 publications

(204 citation statements)

References 51 publications

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“…Also, pharmacological depletion of microglia significantly reduced TSPO availability, which recovered 14 days after discontinuation of the challenge [83]. Neurological conditions characterized by chronic neuroinflammation (e.g., MS) exhibit higher TSPO levels compared to controls (e.g., [85, 86]). Thus, TSPO PET is sensitive to changes in neuroinflammatory state.…”

Section: Using Imaging To Measure Neuroimmune Biomarkersmentioning

confidence: 99%

Imaging Biomarkers of the Neuroimmune System among Substance Use Disorders: A Systematic Review

et al. 2019

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There is tremendous interest in the role of the neuroimmune system and inflammatory processes in substance use disorders (SUDs). Imaging biomarkers of the neuroimmune system in vivo provide a vital translational bridge between preclinical and clinical research. Herein, we examine two imaging techniques that measure putative indices of the neuroimmune system and review their application among SUDs. Positron emission tomography (PET) imaging of 18 kDa translocator protein availability is a marker associated with microglia. Proton magnetic resonance spectroscopy quantification of myo-inositol levels is a putative glial marker found in astrocytes. Neuroinflammatory responses are initiated and maintained by microglia and astrocytes, and thus represent important imaging markers. The goal of this review is to summarize neuroimaging findings from the substance use literature that report data using these markers and discuss possible mechanisms of action. The extant literature indicates abused substances exert diverse and complex neuroimmune effects. Moreover, drug effects may change across addiction stages, i.e. the neuroimmune effects of acute drug administration may differ from chronic use. This burgeoning field has considerable potential to improve our understanding and treatment of SUDs. Future research is needed to determine how targeting the neuroimmune system may improve treatment outcomes.

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Section: Using Imaging To Measure Neuroimmune Biomarkersmentioning

confidence: 99%

Imaging Biomarkers of the Neuroimmune System among Substance Use Disorders: A Systematic Review

et al. 2019

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“…As results, the authors found that intense microglial activation within the hippocampus was correlated with a reduced hippocampal connectivity and severe depression [94]. Moreover, another research group recently quantified the presence of activated macrophages/microglia with simultaneous MR-PET imaging, using the TSPO radio ligand 11 C-PBR28, in patients with both relapsingremitting and secondary progressive MS [95]. Relative to controls, MS subjects exhibited abnormally high brain 11 C-PBR28 binding, the greatest increases being in cortex and cortical lesions, thalamus, hippocampus, and normally appearing white matter (NAWM) [95].…”

Section: Hippocampal Synaptic Plasticity In Experimental Models Of Msmentioning

confidence: 95%

“…Moreover, another research group recently quantified the presence of activated macrophages/microglia with simultaneous MR-PET imaging, using the TSPO radio ligand 11 C-PBR28, in patients with both relapsingremitting and secondary progressive MS [95]. Relative to controls, MS subjects exhibited abnormally high brain 11 C-PBR28 binding, the greatest increases being in cortex and cortical lesions, thalamus, hippocampus, and normally appearing white matter (NAWM) [95]. Interestingly, the authors found that microglia/macrophages activation correlated with reduced cognitive performances in the investigated cohort.…”

Section: Hippocampal Synaptic Plasticity In Experimental Models Of Msmentioning

confidence: 99%

“…Interestingly, the authors found that microglia/macrophages activation correlated with reduced cognitive performances in the investigated cohort. Specifically, increased TSPO levels in the hippocampus, as well as in the thalamus and NAWM were associated with impaired Symbol Digit Modalities Test (SDMT) performances, a measure of information-processing speed [95].…”

Section: Hippocampal Synaptic Plasticity In Experimental Models Of Msmentioning

confidence: 99%

“…Moreover, also demyelinating lesions spreading throughout the brain could indirectly determine a disconnection syndrome, affecting normal hippocampal functional connectivity, both during resting condition and memory tasks. Neuro-inflammation, and in particular microglial activation, could contribute to alter normal hippocampal connectivity with other key brain regions involved in the maintenance of a normal affective state and cognition [94,95].…”

Section: Hippocampal Synaptic Plasticity In Experimental Models Of Msmentioning

confidence: 99%

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Hippocampal neuroplasticity and inflammation: relevance for multiple sclerosis

Mancini

Gaetani

Gregorio

et al. 2017

Mult Scler Demyelinating Disord

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Cognitive impairment is very frequent during multiple sclerosis (MS), involving approximately 40-70% of the patients, with a profound impact on patient's life. It is now established that among the various central nervous system (CNS) structures involved during the course of MS, the hippocampus is particularly sensitive to the detrimental effects of neuroinflammation. Different studies demonstrated hippocampal involvement during MS, in association with depression and cognitive impairment, such as verbal and visuo-spatial memory deficits, even during the earlier phases of the disease. These cognitive alterations could represent the visible consequences of a hidden synaptic impairment. Indeed, neuronal and immune functions are intertwined and the immune system is able to modulate the efficacy of synaptic transmission and the induction of the main forms of synaptic plasticity, such as long term potentiation (LTP). Hippocampal synaptic plasticity has been studied during the last decades as the physiological basis of human learning and memory and its disruption can be associated with behavioral and cognitive abnormalities. The aim of the present work is to review the available evidence about the presence of hippocampal synaptic plasticity alterations in experimental models of MS, specifically during the course of experimental autoimmune encephalomyelitis (EAE) and to discuss their relevance with regard to human MS. Indeed, the failure of synapses to express plasticity during neuroinflammation could potentially lead to a progressive failure of the brain plastic reserve, possibly contributing to disability progression and cognitive impairment during MS.

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Diagnosis of Progressive Multiple Sclerosis From the Imaging Perspective

et al. 2021

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agnetic resonance imaging (MRI) is central in the diagnostic workup of patients with suspected multiple sclerosis (MS) given its high sensitivity to detect disease dissemination in space and over time and its substantial, albeit imperfect, ability to exclude other mimics of MS. From 2001 until 2017, great effort was expended providing successive iterations of the McDonald criteria to define imaging features typical of MS in patients presenting with clinically isolated syndrome (CIS). 1 However, diagnosis of primary progressive (PP) MS remains challenging and is only possible retrospectively based on clinical assessment.Identification of imaging features associated with PPMS and features that predict evolution from relapsing-remitting (RR) MS to secondary progressive (SP) MS is an important unmet need. Given the advent of effective therapies for RRMS that may reduce development of SPMS and limit disability worsening in progressive MS (PMS), 2 the need for such imaging indicators is all the greater.Diagnosis of PMS is limited by difficulties in distinguishing accumulating disability due to inflammatory disease activity from that attributable to degenerative processes associated with SPMS. Moreover, there are no accepted clinical criteria for diagnosing SPMS. 3,4 This need has promoted extensive research in the field of imaging, facilitated by definition of novel MRI sequences, to identify imaging features reflecting pathophysiological mechanisms relevant to the pathobiology of PMS. MethodsIn this review, we report the conclusions of the "Diagnosis of Progressive MS: The Imaging Perspective" workshop held in Milan,

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Neuroinflammatory component of gray matter pathology in multiple sclerosis

Cited by 173 publications

References 51 publications

Imaging Biomarkers of the Neuroimmune System among Substance Use Disorders: A Systematic Review

Imaging Biomarkers of the Neuroimmune System among Substance Use Disorders: A Systematic Review

Hippocampal neuroplasticity and inflammation: relevance for multiple sclerosis

Diagnosis of Progressive Multiple Sclerosis From the Imaging Perspective

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