Fig. 3.

Increased neuron and oligodendrocyte loss in apoE^−/− mice in vivo and in vitro. Robust apoptosis shown by TUNEL staining was observed in the injured spinal cord at 3 days after SCI (A–D). At the injury epicenter, most TUNNEL + apoptotic cells are oligodendrocytes (A, arrows) and neurons (B, arrows). The number of apoptotic cells in the injured epicenter were significantly increased in apoE^−/− mice (C–D) and doubled in apoE^−/− mice compared to WT mice (E). To further examine the effects of endogenous apoE in the survival of neurons and oligodendrocytes, neurons, astrocytes and oligodendrocytes were isolated from postnatal day 3 spinal cord of WT or apoE^−/− mice and co-cultured for 7 days (F–I). In the control culture condition, the morphology and number of neurons (F, G) or oligodendrocytes (H, I) was not significantly different between WT or apoE^−/− mice. Treatment with NMDA resulted in the death of neurons and oligodendrocytes derived from WT (K) and apoE^−/− (L) mice. The surviving neurons (arrows) and oligodendrocytes (arrowheads) from WT or apoE^−/− mice were significantly decreased after NMDA treatment compared to its respective un-treated counterpart (Fig. J–M). Importantly, the numbers of survived neurons or oligodendrocytes from apoE^−/− spinal cord were further decreased to only half of those from WT mice spinal cord after NMDA treatment (M). Scale bar = 50 µm in A, B, 500 µm in C, D, 50 µm in F–I and J–L. Data in E and M represent the mean ± SD, N = 4 (E) and 6 (M), stars represent p < 0.05.