Evidence for a role for apoptosis in central pontine myelinolysis

We have performed an immunocytochemical study of autopsy material from five cases of central pontine myelinolysis (CPM) and five age and sex-matched control subjects with the aim of exploring the possible involvement of apoptotic mechanisms in oligodendrocytes in this condition. We searched for immunoreactivity of glial cells for the apoptotic-related markers death receptor (DR) 3, Bax and Bak, the anti-apoptotic marker Bcl-2 and the cell cycle marker Ki-67. The latter marker was studied because it is known that entry of cells into the cell division cycle can trigger apoptosis if it does not result in mitosis. In CPM there was marked up-regulation of expression of the myelination-related enzyme carbonic anhydrase isoenzyme II and also markedly increased expression of Ki-67 in nuclei of glial cells of all types but particularly those of cells morphologically resembling oligodendrocytes. Despite this, there was no clear increase in density of such cells in CPM. The pro-apoptotic markers Bax, Bak and DR3 were all modestly increased in glial cell cytoplasm in CPM, while there was no change in expression of Bcl-2, which was only sparsely detected in glial cells both in controls and cases of CPM. The ratio of pro- to anti-apoptotic factors would appear from this evidence to have altered in favour of apoptosis in glial cells, most of which had the appearance of oligodendrocytes and many of which expressed Ki-67. We interpret this preliminary study as favouring apoptosis as a mechanism of oligodendrocytic death in CPM. Further study of this mechanism in CPM may lead to identification of factors that could reduce or prevent this rare but serious and often fatal disease.