Apoptosis in cellular compartments of rat spinal cord after severe contusion injury.

Following a controlled, severe contusion lesion to the lower thoracic spinal cord in adult rats, we found that apoptosis occurred in cells located in both gray and white matter. This suggested that both nonneuronal cells, including astrocytes, oligodendroglia and microglia, as well as neurons, might participate in programmed cell death (PCD) following spinal cord injury (SCI). Determination of which cell populations participate, and the kinetics and extent of their involvement might reveal new paradigms for approaches to therapy. Consequently, we assessed the functional deficit, comparing a comprehensive locomotor rating scale (LRS) with the inclined plane test at various times after injury. Using standard histology, along with cell-specific markers, we assessed PCD in different spinal cord segments using several parameters of apoptosis. Our results indicate that hind limb motor function was lost at day 1, and then only gradually and ineffectively (about 10-15%) recovered over the next month. Evidence for increased cell number was present for astrocytes and microglia beginning at day 1 after injury. Over the postinjury time period, apoptotic cells appeared (from day 1 to 14), and peaked (in terms of apoptotic index) on day 3. About one-third were microglia, whereas neurons, both large and small, also underwent apoptosis, again peaking at day 3. However, neurons continued to die and were not replaced by proliferation, so that at day 7, three times as many neurons (as a percentage) underwent PCD compared with the glial compartment. Oligodendrocytes also underwent apoptosis, with a biphasic curve, both at days 3 and 14 following injury. Thus, in addition to immediate, passive necrosis, delayed and apoptotic PCD also occurred in all cell populations in severely injured spinal cord.