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Article

An In Vivo Study of a Rat Fluid-Percussion-Induced Traumatic Brain Injury Model with [11C]PBR28 and [18F]flumazenil PET Imaging

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Lee Kong Chian School of Medicine, Nanyang Technological University, 59 Nanyang Drive, Singapore 636921, Singapore
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Cognitive Neuroimaging Centre, Nanyang Technological University, 59 Nanyang Drive, Singapore 636921, Singapore
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Department of Nuclear Medicine and Molecular Imaging, Radiological Sciences Division, Singapore General Hospital, Outram Road, Singapore 169608, Singapore
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Duke-NUS Medical School, 8 College Road, Singapore 169857, Singapore
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DSO National Laboratories (Kent Ridge), 27 Medical Drive, Singapore 117510, Singapore
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President’s Office, Nanyang Technological University, 50 Nanyang Avenue, Singapore 639798, Singapore
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Department of Clinical Neuroscience, Karolinska Institute, S-171 76 Stockholm, Sweden
*
Authors to whom correspondence should be addressed.
Int. J. Mol. Sci. 2021, 22(2), 951; https://doi.org/10.3390/ijms22020951
Received: 17 December 2020 / Revised: 13 January 2021 / Accepted: 14 January 2021 / Published: 19 January 2021
(This article belongs to the Special Issue Molecular Imaging in Nanomedical Research)
Traumatic brain injury (TBI) modelled by lateral fluid percussion-induction (LFPI) in rats is a widely used experimental rodent model to explore and understand the underlying cellular and molecular alterations in the brain caused by TBI in humans. Current improvements in imaging with positron emission tomography (PET) have made it possible to map certain features of TBI-induced cellular and molecular changes equally in humans and animals. The PET imaging technique is an apt supplement to nanotheranostic-based treatment alternatives that are emerging to tackle TBI. The present study aims to investigate whether the two radioligands, [11C]PBR28 and [18F]flumazenil, are able to accurately quantify in vivo molecular-cellular changes in a rodent TBI-model for two different biochemical targets of the processes. In addition, it serves to observe any palpable variations associated with primary and secondary injury sites, and in the affected versus the contralateral hemispheres. As [11C]PBR28 is a radioligand of the 18 kD translocator protein, the up-regulation of which is coupled to the level of neuroinflammation in the brain, and [18F]flumazenil is a radioligand for GABAA-benzodiazepine receptors, whose level mirrors interneuronal activity and eventually cell death, the use of the two radioligands may reveal two critical features of TBI. An up-regulation in the [11C]PBR28 uptake triggered by the LFP in the injured (right) hemisphere was noted on day 14, while the uptake of [18F]flumazenil was down-regulated on day 14. When comparing the left (contralateral) and right (LFPI) hemispheres, the differences between the two in neuroinflammation were obvious. Our results demonstrate a potential way to measure the molecular alterations in a rodent-based TBI model using PET imaging with [11C]PBR28 and [18F]flumazenil. These radioligands are promising options that can be eventually used in exploring the complex in vivo pharmacokinetics and delivery mechanisms of nanoparticles in TBI treatment. View Full-Text
Keywords: traumatic brain injury (TBI); lateral fluid percussion (LFP); positron emission tomography (PET); neuroinflammation; GABAA-benzodiazepine receptor; PET radioligand; [11C]PBR28; [18F]flumazenil traumatic brain injury (TBI); lateral fluid percussion (LFP); positron emission tomography (PET); neuroinflammation; GABAA-benzodiazepine receptor; PET radioligand; [11C]PBR28; [18F]flumazenil
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MDPI and ACS Style

Ghosh, K.K.; Padmanabhan, P.; Yang, C.-T.; Wang, Z.; Palanivel, M.; Ng, K.C.; Lu, J.; Carlstedt-Duke, J.; Halldin, C.; Gulyás, B. An In Vivo Study of a Rat Fluid-Percussion-Induced Traumatic Brain Injury Model with [11C]PBR28 and [18F]flumazenil PET Imaging. Int. J. Mol. Sci. 2021, 22, 951. https://doi.org/10.3390/ijms22020951

AMA Style

Ghosh KK, Padmanabhan P, Yang C-T, Wang Z, Palanivel M, Ng KC, Lu J, Carlstedt-Duke J, Halldin C, Gulyás B. An In Vivo Study of a Rat Fluid-Percussion-Induced Traumatic Brain Injury Model with [11C]PBR28 and [18F]flumazenil PET Imaging. International Journal of Molecular Sciences. 2021; 22(2):951. https://doi.org/10.3390/ijms22020951

Chicago/Turabian Style

Ghosh, Krishna K., Parasuraman Padmanabhan, Chang-Tong Yang, Zhimin Wang, Mathangi Palanivel, Kian C. Ng, Jia Lu, Jan Carlstedt-Duke, Christer Halldin, and Balázs Gulyás. 2021. "An In Vivo Study of a Rat Fluid-Percussion-Induced Traumatic Brain Injury Model with [11C]PBR28 and [18F]flumazenil PET Imaging" International Journal of Molecular Sciences 22, no. 2: 951. https://doi.org/10.3390/ijms22020951

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