Detection of Neuroinflammation Before Selective Neuronal Loss Appearance After Mild Focal Ischemia Using [F]DPA-714 Imaging

Overview

Journal EJNMMI Res

Date 2018 Jun 10

PMID 29884977

Citations 12

Authors

Natsumi Miyajima

Miwa Ito

Takemi Rokugawa

Hitoshi Iimori

Sotaro Momosaki

Shigeki Omachi

Eku Shimosegawa

Jun Hatazawa

Kohji Abe

Affiliations

Soon will be listed here.

Abstract

Background: Translocator protein (TSPO) imaging can be used to detect neuroinflammation (including microglial activation) after acute cerebral infarction. However, longitudinal changes of TSPO binding after mild ischemia that induces selective neuronal loss (SNL) without acute infarction are not well understood. Here, we performed TSPO imaging with [F]DPA-714 to determine the time course of neuroinflammation and SNL after mild focal ischemia.

Results: Mild focal ischemia was induced by middle cerebral artery occlusion (MCAO) for 20 min. In MCAO rats without acute infarction investigated by 2, 3, 5-triphenyltetrazolium chloride (TTC) staining, in vitro ARG revealed a significant increase of [F]DPA-714 binding in the ipsilateral striatum compared with that in the contralateral side at 1, 2, 3, and 7 days after MCAO. Increased [F]DPA-714 binding was observed in the cerebral cortex penumbra, reaching maximal values at 7 days after MCAO. Activation of striatal microglia and astrocytes was observed with immunohistochemistry of ionized calcium binding adaptor molecule 1 (Iba1) and glial fibrillary acidic protein (GFAP) at 2, 3, and 7 days after MCAO. SNL was investigated with Nissl staining and neuronal nuclei (NeuN) immunostaining and observed in the ischemic core region of the striatum on days 3 and 7 after MCAO. We confirmed that total distribution volume of [F]DPA-714 in the ipsilateral striatum was significantly increased at 2 and 7 days after MCAO using positron emission tomography (PET).

Conclusions: [F]DPA-714 binding measured with in vitro ARG was increased before SNL appeared, and this change was detected by in vivo PET. These findings suggest that TSPO PET imaging might be useful for detection of neuroinflammation leading to SNL after focal ischemia.

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References

Politis M, Su P, Piccini P . Imaging of microglia in patients with neurodegenerative disorders. Front Pharmacol. 2012; 3:96. PMC: 3361961. DOI: 10.3389/fphar.2012.00096. View

Sridharan S, Lepelletier F, Trigg W, Banister S, Reekie T, Kassiou M . Comparative Evaluation of Three TSPO PET Radiotracers in a LPS-Induced Model of Mild Neuroinflammation in Rats. Mol Imaging Biol. 2016; 19(1):77-89. PMC: 5209405. DOI: 10.1007/s11307-016-0984-3. View

Boutin H, Prenant C, Maroy R, Galea J, Greenhalgh A, Smigova A . [18F]DPA-714: direct comparison with [11C]PK11195 in a model of cerebral ischemia in rats. PLoS One. 2013; 8(2):e56441. PMC: 3572061. DOI: 10.1371/journal.pone.0056441. View

Venneti S, Lopresti B, Wiley C . The peripheral benzodiazepine receptor (Translocator protein 18kDa) in microglia: from pathology to imaging. Prog Neurobiol. 2006; 80(6):308-22. PMC: 1849976. DOI: 10.1016/j.pneurobio.2006.10.002. View

Moskowitz M, Lo E, Iadecola C . The science of stroke: mechanisms in search of treatments. Neuron. 2010; 67(2):181-98. PMC: 2957363. DOI: 10.1016/j.neuron.2010.07.002. View

Fujioka M, Taoka T, Matsuo Y, Mishima K, Ogoshi K, Kondo Y . Magnetic resonance imaging shows delayed ischemic striatal neurodegeneration. Ann Neurol. 2003; 54(6):732-47. DOI: 10.1002/ana.10751. View

Harhausen D, Sudmann V, Khojasteh U, Muller J, Zille M, Graham K . Specific imaging of inflammation with the 18 kDa translocator protein ligand DPA-714 in animal models of epilepsy and stroke. PLoS One. 2013; 8(8):e69529. PMC: 3732268. DOI: 10.1371/journal.pone.0069529. View

Smith M, van der Maesen K, Somera F . Macrophage and microglial responses to cytokines in vitro: phagocytic activity, proteolytic enzyme release, and free radical production. J Neurosci Res. 1998; 54(1):68-78. DOI: 10.1002/(SICI)1097-4547(19981001)54:1<68::AID-JNR8>3.0.CO;2-F. View

Ruan Y, Ling G, Zhang J, Xu Z . Apoptosis in the adult striatum after transient forebrain ischemia and the effects of ischemic severity. Brain Res. 2003; 982(2):228-40. DOI: 10.1016/s0006-8993(03)03021-x. View

10.

Boutin H, Murray K, Pradillo J, Maroy R, Smigova A, Gerhard A . 18F-GE-180: a novel TSPO radiotracer compared to 11C-R-PK11195 in a preclinical model of stroke. Eur J Nucl Med Mol Imaging. 2014; 42(3):503-11. DOI: 10.1007/s00259-014-2939-8. View

11.

Cagnin A, Gerhard A, Banati R . In vivo imaging of neuroinflammation. Eur Neuropsychopharmacol. 2002; 12(6):581-6. DOI: 10.1016/s0924-977x(02)00107-4. View

12.

Zhang Z, Chopp M, Powers C . Temporal profile of microglial response following transient (2 h) middle cerebral artery occlusion. Brain Res. 1997; 744(2):189-98. DOI: 10.1016/S0006-8993(96)01085-2. View

13.

Hughes J, Beech J, Jones P, Wang D, Menon D, Baron J . Mapping selective neuronal loss and microglial activation in the salvaged neocortical penumbra in the rat. Neuroimage. 2009; 49(1):19-31. DOI: 10.1016/j.neuroimage.2009.08.047. View

14.

Bradvik B, Sonesson B, Holtas S . Spatial impairment following right hemisphere transient ischaemic attacks in patients without carotid artery stenosis. Acta Neurol Scand. 1989; 80(5):411-8. DOI: 10.1111/j.1600-0404.1989.tb03902.x. View

15.

Wimberley C, Lavisse S, Brulon V, Peyronneau M, Leroy C, Bodini B . Impact of Endothelial 18-kDa Translocator Protein on the Quantification of F-DPA-714. J Nucl Med. 2017; 59(2):307-314. DOI: 10.2967/jnumed.117.195396. View

16.

Lee D, Yue X, Ibrahim W, Lentz M, Peterson K, Jagoda E . Lack of neuroinflammation in the HIV-1 transgenic rat: an [(18)F]-DPA714 PET imaging study. J Neuroinflammation. 2015; 12:171. PMC: 4574011. DOI: 10.1186/s12974-015-0390-9. View

17.

Nodari L, Ferrari D, Giani F, Bossi M, Rodriguez-Menendez V, Tredici G . Long-term survival of human neural stem cells in the ischemic rat brain upon transient immunosuppression. PLoS One. 2010; 5(11):e14035. PMC: 2988794. DOI: 10.1371/journal.pone.0014035. View

18.

Rupalla K, Allegrini P, Sauer D, Wiessner C . Time course of microglia activation and apoptosis in various brain regions after permanent focal cerebral ischemia in mice. Acta Neuropathol. 1998; 96(2):172-8. DOI: 10.1007/s004010050878. View

19.

Miles A, Knuckey N . Apoptotic neuronal death following cerebral ischaemia. J Clin Neurosci. 2008; 5(2):125-45. DOI: 10.1016/s0967-5868(98)90027-3. View

20.

Juurlink B, Sweeney M . Mechanisms that result in damage during and following cerebral ischemia. Neurosci Biobehav Rev. 1997; 21(2):121-8. DOI: 10.1016/s0149-7634(96)00001-2. View