SELECTIVE ALTERATIONS IN THE CELLULAR-DISTRIBUTION OF APOLIPOPROTEIN-E IMMUNOREACTIVITY FOLLOWING TRANSIENT CEREBRAL-ISCHEMIA IN THE RAT

The aim of this study was to examine the cellular localization and alt erations of apolipoprotein E (apoE) following a transient ischaemic in sult using immunohistochemistry. Transient cerebral ischaemia was indu ced in Wistar rats by occlusion of both carotid arteries with hypotens ion followed by reperfusion for 4 h (n=5), 24 h (n=5) or 72 h (n=6). I n sham-operated animals (n=9), the carotids were not occluded. In this model, ischaemia for 15 min results in selective neuronal damage in t he caudate nucleus and neocortex (24 h after reperfusion) and the hipp ocampal CA1 pyramidal cells (72 h after reperfusion) while there is mi nimal damage in other areas such as the CA3 hippocampal region. In sha m animals, apoE immunoreactivity was confined to astrocytes and their processes. ApoE immunoreactivity was not altered at 4h post-ischaemic reperfusion. At 24 h reperfusion, intense apoE staining of the cytopla sm of astrocytes and neuropil within the caudate and neocortex was obs erved and at 72 h reperfusion apoE stained neuronal cell bodies within these regions. Within the CA1 region at 24 h reperfusion, there was i ncreased immunoreactivity of the cytoplasm of astrocytes and the neuro pil was more intensely stained compared with sham animals. At 72 h rep erfusion, intense apoE staining of pyramidal cell bodies and dendrites was consistently observed in the CA1 region of the hippocampus. In co ntrast, at 72 h reperfusion, apoE staining of astrocytic processes was dramatically reduced in the CA1 region although GFAP staining indicat ed their preservation, The results demonstrate that following an ischa emic insult apoE is localized to degenerating neurons and their proces ses, This may indicate an inherent protective response of cells to inj ury, Alternatively, the results are consistent with the hypothesis tha t apoE is synthesized and released by astrocytes and taken up by neuro ns following injury.