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European Journal of Nuclear Medicine and Molecular Imaging

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01-01-2004 | Original Article

Characterisation of [¹²³I]iomazenil distribution in a rat model of focal cerebral ischaemia in relation to histopathological findings

Authors: Tomohito Kaji, Yuji Kuge, Chiaki Yokota, Masafumi Tagaya, Hiroyasu Inoue, Tohru Shiga, Kazuo Minematsu, Nagara Tamaki

Published in: European Journal of Nuclear Medicine and Molecular Imaging | Issue 1/2004

Abstract

Iodine-123 labelled iomazenil ([¹²³I]IMZ) has been reported to be a useful marker of neuronal viability. The brain distribution of [¹²³I]IMZ, however, has not been correlated with the pathophysiological response in detail after an ischaemic insult. To characterise [¹²³I]IMZ as a marker of neuronal viability, we compared its brain distribution with cyclooxygenase-2 (COX-2) expression, DNA fragmentation and cellular integrity. [¹²³I]IMZ and [¹²⁵I]IMP were injected into rats with focal cerebral ischaemia for the purpose of dual-tracer autoradiography. COX-2 and microtubule-associated protein-2 (MAP-2, a marker of cellular integrity) were immunostained. In situ DNA polymerase-I-dependent dUTP incorporation into damaged DNA was used as an indicator of DNA fragmentation. Lesion to normal ratios (LNRs) for [¹²³I]IMP and [¹²⁵I]IMZ were calculated. [¹²³I]IMZ accumulation was preserved in several regions with impaired [¹²³I]IMP accumulation. COX-2 expression was occasionally observed, whereas neither DNA fragmentation nor MAP-2 denaturation was detected in these regions. DNA fragmentation and impaired MAP-2 immunostaining were observed only in the regions with reduced LNRs for both tracers. The LNR for [¹²³I]IMZ was significantly lower in regions with impaired MAP-2 immunostaining (0.120±0.152, P<0.0001), in regions positive for dUTP incorporation (0.488±0.166, P<0.0001) and in regions positive for COX-2 expression (0.626±0.186, P<0.001) than in histologically normal regions (0.784±0.213). Thus, neuronal DNA is still intact and cellular integrity is maintained in the ischaemic regions with preserved [¹²³I]IMZ accumulation. The impairment of [¹²³I]IMZ accumulation precedes DNA fragmentation and denaturation of cellular integrity. These results provide the molecular basis of [¹²³I]IMZ distribution.

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Title: Characterisation of [123I]iomazenil distribution in a rat model of focal cerebral ischaemia in relation to histopathological findings
Authors: Tomohito Kaji
Yuji Kuge
Chiaki Yokota
Masafumi Tagaya
Hiroyasu Inoue
Tohru Shiga
Kazuo Minematsu
Nagara Tamaki
Publication date: 01-01-2004
Publisher: Springer-Verlag
Published in: European Journal of Nuclear Medicine and Molecular Imaging / Issue 1/2004
Print ISSN: 1619-7070
Electronic ISSN: 1619-7089
DOI: https://doi.org/10.1007/s00259-003-1319-6

At a glance: The STEP trials

Springer Medicine

Characterisation of [¹²³I]iomazenil distribution in a rat model of focal cerebral ischaemia in relation to histopathological findings

Abstract

At a glance: The STEP trials

Springer Medicine

Abstract

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