Serial quantitative TSPO-targeted PET reveals peak microglial activation up to 2 weeks after an epileptogenic brain insult

Mirjam Brackhan, Pablo Bascun ana, Johannes M. Postema, Tobias L. Ross, Frank M. Bengel, Marion Bankstahl, Jens P. Bankstahl

Research output: Contribution to journalArticle

Abstract

Experimental and clinical evidence suggests that neuroinflammation, triggered by epileptogenic insults, contributes to seizure development. We used translocator protein-targeted molecular imaging to obtain further insights into the role of microglial activation during epileptogenesis. Methods: As epileptogenic insult, a status epilepticus (SE) was induced in rats by lithium pilocarpine. Rats were subjected to 11C-PK11195 PET scans before SE; at 4 h after SE; at 1, 2, 5, 7, 14, and 22 d after SE; and at 14-16 wk after SE. For data evaluation, brain regions were outlined by coregistration with a standard rat brain atlas, and percentage injected dose/cm3 and binding potential (simplified reference tissue model with cerebellar gray matter as a reference region) were calculated. For autoradiography and immunohistochemical evaluation, additional rats were decapitated without prior SE or 2, 5, or 14 d after SE. Results: After SE, increases in 11C-PK11195 uptake and binding potential were evident in epileptogenesis-associated brain regions, such as the hippocampus, thalamus, or piriform cortex, but not in the cerebellum beginning at 2-5 d and persisting at least 3 wk after SE. Maximal regional signal was observed at 1-2 wk after SE. Autoradiography confirmed the spatiotemporal profile. Immunohistochemical evaluation revealed microglial and astroglial activation as well as neuronal cell loss in epileptogenesis-associated brain regions at all investigated time points. The time course of microglial activation was consistent with that demonstrated by tracer techniques. Conclusion: Translocator protein-targeted PET is a reliable tool for identifying brain inflammation during epileptogenesis. Neuroinflammation mainly affects brain regions commonly associated with seizure generation and spread. Definition of the time profile of neuroinflammation may facilitate the development of inflammation-targeted, antiepileptogenic therapy.

Original languageEnglish (US)
Pages (from-to)1302-1308
Number of pages7
JournalJournal of Nuclear Medicine
Volume57
Issue number8
DOIs
StatePublished - Aug 1 2016
Externally publishedYes

Fingerprint

Status Epilepticus
Brain
Autoradiography
Seizures
Pilocarpine
Molecular Imaging
Atlases
Encephalitis
Thalamus
Lithium
Positron-Emission Tomography
Cerebellum
Hippocampus
Proteins
Inflammation

Keywords

  • Brain inflammation
  • Epileptogenesis
  • Microglia activation
  • PET
  • TSPO

ASJC Scopus subject areas

  • Medicine(all)
  • Radiology Nuclear Medicine and imaging

Cite this

Brackhan, M., Bascun ana, P., Postema, J. M., Ross, T. L., Bengel, F. M., Bankstahl, M., & Bankstahl, J. P. (2016). Serial quantitative TSPO-targeted PET reveals peak microglial activation up to 2 weeks after an epileptogenic brain insult. Journal of Nuclear Medicine, 57(8), 1302-1308. https://doi.org/10.2967/jnumed.116.172494

Serial quantitative TSPO-targeted PET reveals peak microglial activation up to 2 weeks after an epileptogenic brain insult. / Brackhan, Mirjam; Bascun ana, Pablo; Postema, Johannes M.; Ross, Tobias L.; Bengel, Frank M.; Bankstahl, Marion; Bankstahl, Jens P.

In: Journal of Nuclear Medicine, Vol. 57, No. 8, 01.08.2016, p. 1302-1308.

Research output: Contribution to journalArticle

Brackhan, M, Bascun ana, P, Postema, JM, Ross, TL, Bengel, FM, Bankstahl, M & Bankstahl, JP 2016, 'Serial quantitative TSPO-targeted PET reveals peak microglial activation up to 2 weeks after an epileptogenic brain insult', Journal of Nuclear Medicine, vol. 57, no. 8, pp. 1302-1308. https://doi.org/10.2967/jnumed.116.172494
Brackhan, Mirjam ; Bascun ana, Pablo ; Postema, Johannes M. ; Ross, Tobias L. ; Bengel, Frank M. ; Bankstahl, Marion ; Bankstahl, Jens P. / Serial quantitative TSPO-targeted PET reveals peak microglial activation up to 2 weeks after an epileptogenic brain insult. In: Journal of Nuclear Medicine. 2016 ; Vol. 57, No. 8. pp. 1302-1308.
@article{2e01843545274dd2a1e8c735809481d7,
title = "Serial quantitative TSPO-targeted PET reveals peak microglial activation up to 2 weeks after an epileptogenic brain insult",
abstract = "Experimental and clinical evidence suggests that neuroinflammation, triggered by epileptogenic insults, contributes to seizure development. We used translocator protein-targeted molecular imaging to obtain further insights into the role of microglial activation during epileptogenesis. Methods: As epileptogenic insult, a status epilepticus (SE) was induced in rats by lithium pilocarpine. Rats were subjected to 11C-PK11195 PET scans before SE; at 4 h after SE; at 1, 2, 5, 7, 14, and 22 d after SE; and at 14-16 wk after SE. For data evaluation, brain regions were outlined by coregistration with a standard rat brain atlas, and percentage injected dose/cm3 and binding potential (simplified reference tissue model with cerebellar gray matter as a reference region) were calculated. For autoradiography and immunohistochemical evaluation, additional rats were decapitated without prior SE or 2, 5, or 14 d after SE. Results: After SE, increases in 11C-PK11195 uptake and binding potential were evident in epileptogenesis-associated brain regions, such as the hippocampus, thalamus, or piriform cortex, but not in the cerebellum beginning at 2-5 d and persisting at least 3 wk after SE. Maximal regional signal was observed at 1-2 wk after SE. Autoradiography confirmed the spatiotemporal profile. Immunohistochemical evaluation revealed microglial and astroglial activation as well as neuronal cell loss in epileptogenesis-associated brain regions at all investigated time points. The time course of microglial activation was consistent with that demonstrated by tracer techniques. Conclusion: Translocator protein-targeted PET is a reliable tool for identifying brain inflammation during epileptogenesis. Neuroinflammation mainly affects brain regions commonly associated with seizure generation and spread. Definition of the time profile of neuroinflammation may facilitate the development of inflammation-targeted, antiepileptogenic therapy.",
keywords = "Brain inflammation, Epileptogenesis, Microglia activation, PET, TSPO",
author = "Mirjam Brackhan and {Bascun ana}, Pablo and Postema, {Johannes M.} and Ross, {Tobias L.} and Bengel, {Frank M.} and Marion Bankstahl and Bankstahl, {Jens P.}",
year = "2016",
month = "8",
day = "1",
doi = "10.2967/jnumed.116.172494",
language = "English (US)",
volume = "57",
pages = "1302--1308",
journal = "Journal of Nuclear Medicine",
issn = "0161-5505",
publisher = "Society of Nuclear Medicine Inc.",
number = "8",

}

TY - JOUR

T1 - Serial quantitative TSPO-targeted PET reveals peak microglial activation up to 2 weeks after an epileptogenic brain insult

AU - Brackhan, Mirjam

AU - Bascun ana, Pablo

AU - Postema, Johannes M.

AU - Ross, Tobias L.

AU - Bengel, Frank M.

AU - Bankstahl, Marion

AU - Bankstahl, Jens P.

PY - 2016/8/1

Y1 - 2016/8/1

N2 - Experimental and clinical evidence suggests that neuroinflammation, triggered by epileptogenic insults, contributes to seizure development. We used translocator protein-targeted molecular imaging to obtain further insights into the role of microglial activation during epileptogenesis. Methods: As epileptogenic insult, a status epilepticus (SE) was induced in rats by lithium pilocarpine. Rats were subjected to 11C-PK11195 PET scans before SE; at 4 h after SE; at 1, 2, 5, 7, 14, and 22 d after SE; and at 14-16 wk after SE. For data evaluation, brain regions were outlined by coregistration with a standard rat brain atlas, and percentage injected dose/cm3 and binding potential (simplified reference tissue model with cerebellar gray matter as a reference region) were calculated. For autoradiography and immunohistochemical evaluation, additional rats were decapitated without prior SE or 2, 5, or 14 d after SE. Results: After SE, increases in 11C-PK11195 uptake and binding potential were evident in epileptogenesis-associated brain regions, such as the hippocampus, thalamus, or piriform cortex, but not in the cerebellum beginning at 2-5 d and persisting at least 3 wk after SE. Maximal regional signal was observed at 1-2 wk after SE. Autoradiography confirmed the spatiotemporal profile. Immunohistochemical evaluation revealed microglial and astroglial activation as well as neuronal cell loss in epileptogenesis-associated brain regions at all investigated time points. The time course of microglial activation was consistent with that demonstrated by tracer techniques. Conclusion: Translocator protein-targeted PET is a reliable tool for identifying brain inflammation during epileptogenesis. Neuroinflammation mainly affects brain regions commonly associated with seizure generation and spread. Definition of the time profile of neuroinflammation may facilitate the development of inflammation-targeted, antiepileptogenic therapy.

AB - Experimental and clinical evidence suggests that neuroinflammation, triggered by epileptogenic insults, contributes to seizure development. We used translocator protein-targeted molecular imaging to obtain further insights into the role of microglial activation during epileptogenesis. Methods: As epileptogenic insult, a status epilepticus (SE) was induced in rats by lithium pilocarpine. Rats were subjected to 11C-PK11195 PET scans before SE; at 4 h after SE; at 1, 2, 5, 7, 14, and 22 d after SE; and at 14-16 wk after SE. For data evaluation, brain regions were outlined by coregistration with a standard rat brain atlas, and percentage injected dose/cm3 and binding potential (simplified reference tissue model with cerebellar gray matter as a reference region) were calculated. For autoradiography and immunohistochemical evaluation, additional rats were decapitated without prior SE or 2, 5, or 14 d after SE. Results: After SE, increases in 11C-PK11195 uptake and binding potential were evident in epileptogenesis-associated brain regions, such as the hippocampus, thalamus, or piriform cortex, but not in the cerebellum beginning at 2-5 d and persisting at least 3 wk after SE. Maximal regional signal was observed at 1-2 wk after SE. Autoradiography confirmed the spatiotemporal profile. Immunohistochemical evaluation revealed microglial and astroglial activation as well as neuronal cell loss in epileptogenesis-associated brain regions at all investigated time points. The time course of microglial activation was consistent with that demonstrated by tracer techniques. Conclusion: Translocator protein-targeted PET is a reliable tool for identifying brain inflammation during epileptogenesis. Neuroinflammation mainly affects brain regions commonly associated with seizure generation and spread. Definition of the time profile of neuroinflammation may facilitate the development of inflammation-targeted, antiepileptogenic therapy.

KW - Brain inflammation

KW - Epileptogenesis

KW - Microglia activation

KW - PET

KW - TSPO

UR - http://www.scopus.com/inward/record.url?scp=84982822081&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84982822081&partnerID=8YFLogxK

U2 - 10.2967/jnumed.116.172494

DO - 10.2967/jnumed.116.172494

M3 - Article

C2 - 27056616

AN - SCOPUS:84982822081

VL - 57

SP - 1302

EP - 1308

JO - Journal of Nuclear Medicine

JF - Journal of Nuclear Medicine

SN - 0161-5505

IS - 8

ER -