01.01.2004 | Original Article
Characterisation of [123I]iomazenil distribution in a rat model of focal cerebral ischaemia in relation to histopathological findings
Erschienen in: European Journal of Nuclear Medicine and Molecular Imaging | Ausgabe 1/2004
Einloggen, um Zugang zu erhaltenAbstract
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.
Anzeige