ASSESSMENT OF THE DISTRIBUTION OF MITOCHONDRIAL RIBOSOMAL-RNA IN MELAS AND IN THROMBOTIC CEREBRAL INFARCTS BY IN-SITU HYBRIDIZATION

In situ hybridization to mitochondrial ribosomal RNA (rRNA) has been u sed to study the distribution of mitochondria in paraffin-embedded aut opsy brain tissue from two patients with MELAS (mitochondrial myopathy , encephalopathy, lactic acidosis, and stroke-like episodes) and other organs from one of the patients. Comparison of in situ hybridization and electron microscopic findings in an antemortem biopsy specimen of pylorus from the latter patient showed a close correspondence between the distribution of hybridization signal on light microscopy and of mi tochondria in ultrathin sections. Strong hybridization signal was pres ent over smooth muscle fibres of the muscularis externa, which contain ed abnormal accumulations of mitochondria on electron microscopy. Hybr idization to sections of skeletal muscle confirmed previous reports of 'ragged-red' fibres in this disorder and of mitochondrial accumulatio ns in the malls of intramuscular blood vessels. To try to elucidate th e role of vessel wall accumulation of mitochondria in the genesis of t he stroke-like lesions, the distribution of mitochondrial rRNA was ass essed in sections of brain from both of the cases of MELAS and several cases of atherothrombotic cerebrovascular disease. Blood vessels in a nd adjacent to the cerebral lesions of MELAS showed strong hybridizati on signal with the mitochondrial probes, as was also seen in infarcts of various ages in the control brains. Only weak signal was present in the malls of blood vessels distant from the lesions, in both MELAS an d control brains. These findings suggest that mitochondria accumulate in vascular endothelium and tunica media as a normal response to cereb ral infarction or ischaemia. The accumulation of mitochondria in the c erebral lesions of MELAS may, at least in part, be a reaction to the d estructive effects of the underlying metabolic dysfunction.