Temporal‐spatial dynamics in oligodendrocyte and glial progenitor cell numbers throughout ventrolateral white matter following contusion spinal cord injury

Abstract

The aim of this study was to systematically determine the spatial distribution of oligodendrocytes (CC1(+)) and glial progenitor cells (NG2(+)) throughout the ventral lateral funiculi (VLF) of adult rat thoracic spinal cord white matter over the course of spontaneous hindlimb locomotor recovery following moderate contusion injury. We used the optical fractionator technique to establish an unbiased estimate of total CC1(+) and NG2(+) cell numbers throughout equivalent segments of VLF from normal and injured spinal cords at designated time points. The results demonstrated a greater than 60% loss of oligodendrocytes and a 50% increase in NG2(+) cells 2 days postinjury. Subsequently, there was a significant increase in oligodendrocytes 7 days postinjury that continued throughout the time course of our experiments (42 days) when the total numbers recovered to 80% of controls. Conversely, NG2(+) cell numbers progressively declined after 2 days postinjury but remained significantly higher than controls throughout the experiments. The pattern of acute loss and repopulation of oligodendrocytes in the VLF paralleled the initial recovery of hindlimb weight-bearing function. Whether such improvement is directly related to NG2(+) cell differentiation into functional oligodendrocytes is uncertain. However, of critical importance is that significant cellular dynamics occurred primarily distal to the injury, and these changes were mirrored by significant alterations in the expression of mature myelin proteins. This infers that site-specific genetic or cellular interventions designed to enhance locomotor recovery by fostering remyelination of spared and/or newly established relay circuits may need to target not only the injury site but also rostrocaudal regions.