ro-16-0154 and Acute-Disease

To investigate the utility of neuroreceptor imaging in ischaemic cerebrovascular disorders, dual-tracer autoradiography using 99Tcm-hexamethylpropyleneamine oxime (HMPAO) for the evaluation of cerebral blood flow and 125I-iomazenil for the evaluation of central-type benzodiazepine receptor density was performed in experimental brain ischaemia created by occlusion of the unilateral middle cerebral artery of the rat. In the acute phase of ischaemia, 125I-iomazenil accumulation showed less of a decrease than 99Tcm-HMPAO in the cerebral cortex of the lateral convexity and in the lateral segment of the caudate putamen in the lesioned cerebral hemisphere. In the sub-acute phase, both 125I-iomazenil and 99Tcm-HMPAO accumulation increased in the lesion compared with the acute phase. A large accumulation of 99Tcm-HMPAO and 125I-iomazenil in the lesion was considered to be due to luxury perfusion and penetration of 125I-iomazenil hydrophilic metabolites from the blood into the brain tissue through the altered blood-brain barrier. In the chronic phase, 125I-iomazenil accumulation showed a more marked decrease than 99Tcm-HMPAO in the lesion. Moreover, the ipsilateral thalamus, which is remote from the lesion, revealed decreased 125I-iomazenil accumulation despite normal 99Tcm-HMPAO accumulation. Since the central-type benzodiazepine receptors are principally located not on the glial cells but on the neurons, the receptor density may exhibit a change that parallels the neuron density. These results suggest that central-type benzodiazepine receptor imaging is useful for the evaluation of neuronal damage when used in conjunction with brain perfusion imaging in ischaemic cerebrovascular disorders, except in the sub-acute phase.

Topics: Acute Disease; Animals; Autoradiography; Brain; Brain Ischemia; Chronic Disease; Flumazenil; Functional Laterality; Iodine Radioisotopes; Male; Organ Specificity; Organotechnetium Compounds; Oximes; Radionuclide Imaging; Rats; Rats, Inbred Strains; Receptors, GABA-A; Technetium Tc 99m Exametazime