In vivo imaging of microglial activation using a peripheral benzodiazepine receptor ligand: [11C]PK-11195 and animal PET following ethanol injury in rat striatum

Toyama, Hiroshi; Hatano, Kentaro; Suzuki, Hiromi; Ichise, Masanori; Momosaki, Sotaro; Kudo, Gen; Ito, Fumitaka; Kato, Takashi; Yamaguchi, Hiroshi; Katada, Kazuhiro; Sawada, Makoto; Ito, Kengo

doi:10.1007/s12149-008-0136-1

Cited by 25 publications

(24 citation statements)

References 27 publications

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“…The distribution pattern of [ 11 C] DAC was in agreement with TSPO distribution in the spinal cords of EAE. Pharmacological probes that bind TSPO have been used extensively to study receptor-binding parameters in brain tissues Venneti et al 2006;Toyama et al 2008). It is necessary to determine the cell types responsible for increased probe binding.…”

Section: Discussionmentioning

confidence: 99%

“…Radiolabeled imaging agents have permitted sensitive detection of TSPO when applied to autoradiographic and positron emission tomography (PET) techniques (Zhang et al 2007a, b;Yanamoto et al 2010;. It has been reported that [ 11 C] PK11195, the most commonly used TSPO probe, increased binding in patients with stroke (Chauveau et al 2009;Thiel et al 2010) and traumatic brain injury (Toyama et al 2008;Folkersma et al 2009), and in patients with chronic neurodegenerative conditions, including Huntington's disease Tai et al 2007), Parkinson's disease Bartels and Leenders 2007) and MS (Agnello et al 2000;Banati et al 2000). Unfortunately, [ 11 C] PK11195 presents some limitations, including a high level of nonspecific binding and poor signal-to-noise ratio (Chauveau et al 2008), a series of new and alternative radiolabeled ligands were developed to establish PET probes suitable for imaging TSPO in the living CNS.…”

Section: Introductionmentioning

confidence: 99%

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[11C]DAC-PET for Noninvasively Monitoring Neuroinflammation and Immunosuppressive Therapy Efficacy in Rat Experimental Autoimmune Encephalomyelitis Model

Xie

Yamasaki

Ichimaru

et al. 2011

J Neuroimmune Pharmacol

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Neuroimaging measures have potential for monitoring neuroinflammation to guide treatment before the occurrence of significant functional impairment or irreversible neuronal damage in multiple sclerosis (MS). N-Benzyl-N-methyl-2-(7-[(11)C]methyl-8-oxo-2-phenyl-7,8-dihydro-9H-purin-9-yl) acetamide ([(11)C]DAC), a new developed positron emission tomography (PET) probe for translocator protein 18 kDa (TSPO), has been adopted to evaluate the neuroinflammation and treatment effects of experimental autoimmune encephalomyelitis (EAE), an animal model of MS. [(11)C]DAC-PET enabled visualization of neuroinflammation lesion of EAE by tracing TSPO expression in the spinal cords; the maximal uptake value reached in day 11 and 20 EAE rats with profound inflammatory cell infiltration compared with control, day 0 and 60 EAE rats. Biodistribution studies and in vitro autoradiography confirmed these in vivo imaging results. Doubling immunohistochemical studies showed the infiltration and expansion of CD4+ T cells and CD11b+ microglia; CD68+ macrophages were responsible for the increased TSPO levels visualized by [(11)C]DAC-PET. Furthermore, mRNA level analysis of the cytokines by quantitative reverse-transcription polymerase chain reaction (qRT-PCR) revealed that TSPO+/CD4 T cells, TSPO+ microglia and TSPO+ macrophages in EAE spinal cords were activated and secreted multiple proinflammation cytokines to mediate inflammation lesions of EAE. EAE rats treated with an immunosuppressive agent: 2-amino-2-[2-(4-octylphenyl)ethyl] propane-1,3-diolhydrochloride (FTY720), which exhibited an absence of inflammatory cell infiltrates, displaying a faint radioactive signal compared with the high accumulation of untreated EAE rats. These results indicated that [(11)C] DAC-PET imaging is a sensitive tool for noninvasively monitoring the neuroinflammation response and evaluating therapeutic interventions in EAE.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

[11C]DAC-PET for Noninvasively Monitoring Neuroinflammation and Immunosuppressive Therapy Efficacy in Rat Experimental Autoimmune Encephalomyelitis Model

Xie

Yamasaki

Ichimaru

et al. 2011

J Neuroimmune Pharmacol

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“…However, microglia in neonatal or young animals might also act as neurotoxicity, depending on the condition of microglial activation. Sawada H. et al (2010) reported that LPS-activated neonatal microglia showed the neurotoxic phenotype in an ethanol-induced brain injury model produced by the stereotaxic injection of ethanol into the mouse striatum (Takeuchi et al, 1998;Toyama et al, 2008;Fig. 4).…”

Section: Neurotoxic Role Of Microgliamentioning

confidence: 99%

Role of Microglia in Inflammatory Process in Parkinson’s Disease

Sawada¹,

Suzuki²,

Ono³

et al. 2011

Etiology and Pathophysiology of Parkinson's Disease

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“…Sawada et al [manuscript in preparation] examined whether or not LPS-activated neonatal microglia also show the neuroprotective phenotype in an ethanol-induced brain injury model [8][9][10] produced by the stereotaxic injection of 100% ethanol (2 l) into the mouse striatum. This local injection of ethanol produced more severe neuronal damage than seen in the MPTP-induced PD model.…”

Section: Neurotoxic Phenotype Of Microglia Activated By Lps In Neonatmentioning

confidence: 99%

Neuroprotective and Neurotoxic Phenotypes of Activated Microglia in Neonatal Mice with Respective MPTP- and Ethanol-Induced Brain Injury

Sawada

Suzuki²,

Nagatsu³

et al. 2010

Neurodegener Dis

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Activated microglia play important roles in the inflammatory process and progression in Parkinson’s disease. These cells produce various cytokines, nitric oxide, and neurotrophins, which are pleiotropic in their action, i.e., neuroprotective or neurotoxic. In an in vivo study on a mouse model with nigrostriatal lesions produced by the administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), microglia activated by systemic lipopolysaccharide (LPS) were neurotoxic toward dopamine neurons in aged mice, but unexpectedly, neuroprotective in neonatal mice. In contrast to microglia in the MPTP model, LPS-activated microglia in neonatal mice in a model made by the stereotaxic injection of ethanol into the striatum were neurotoxic, and systemic LPS administration in the ethanol-injury model caused marked increases both in the volume of necrotic lesions and in the number of degenerative neurons in the striatum. Thus, activated microglia in the neonatal mouse brain play either a neuroprotective or neurotoxic role depending on the type of brain injury.

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In vivo imaging of microglial activation using a peripheral benzodiazepine receptor ligand: [11C]PK-11195 and animal PET following ethanol injury in rat striatum

Abstract: These results suggest that [(11)C]PK-11195 PET imaging would be a useful tool for evaluating microglial activation in a rat brain injury model.

Cited by 25 publications

References 27 publications

[11C]DAC-PET for Noninvasively Monitoring Neuroinflammation and Immunosuppressive Therapy Efficacy in Rat Experimental Autoimmune Encephalomyelitis Model

[11C]DAC-PET for Noninvasively Monitoring Neuroinflammation and Immunosuppressive Therapy Efficacy in Rat Experimental Autoimmune Encephalomyelitis Model

Role of Microglia in Inflammatory Process in Parkinson’s Disease

Neuroprotective and Neurotoxic Phenotypes of Activated Microglia in Neonatal Mice with Respective MPTP- and Ethanol-Induced Brain Injury

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