Abstracts

Rationale: Scar astrocytes are the major constituent of the glial scars that characterize diverse brain diseases, including mesial temporal lobe epilepsy (MTLE) with hippocampal sclerosis (HS). Although the origin of scar astrocytes from reactive glia is well established, detailed characterization of the pathway is lacking: it is possible that scar astrocytes could originate from either gradual transformation from reactive astrocytes, or abruptly, after cell division. Methods: To check the hypothesis that scar astrocytes originate after astrocyte division, we injected bromodeoxyuridine (BrdU), which labels mitotic cells, in the acute period after a brain insult in rat models of brain disease (pilocarpine-induced status epilepticus and ischemic damage) and examined the resulting glial scar for a presence of BrdU-positive cells. We also compared the immune profile of scar astrocytes in HS with their counterparts in experimental conditions. Results: Many scar astrocytes incorporated BrdU in both experimental paradigms. Scar astrocytes significantly differ from their progenitors, protoplasmic astrocytes, in both their shape and immune profile. Scar astrocytes lack small filopodia-like processes, the major astrocytic compartment responsible for neuron-glia interaction. Non-mitotic reactive astrocytes revealed a reduction in the amount of these small processes, whereas dividing reactive astrocytes were completely devoid of them. Comparison of cell shape and immune profile of scar astrocytes in HS and animals showed that rat and human cells were very similar in their morphological and protein phenotype. Conclusions: Based on obtained results we propose that in HS as in other human glial scars, scar astrocytes originate from reactive astrocytes after division.