ASTROCYTE RESPONSE AND TRANSFORMING GROWTH-FACTOR-BETA LOCALIZATION IN ACUTE SPINAL-CORD INJURY

Study Design. An experimental histologic and immunohistological invest igation of acute spinal cord injury was performed in a rat model. Obje ctive. This study determined (1) the immediate cellular and molecular responses within the spinal cord that result from a clinically relevan t compression injury, (2) the acute astrocytic response to injury usin g the astrocyte specific GFAP antibody, and (3) the temporal pattern o f cellular and extracellular localization of transforming growth facto r-beta1 (TGF-beta1) within the spinal cord injury zone immediately aft er injury. Summary of Background Data. Ultimate neurologic outcome fro m spinal cord injury results from both the primary mechanical trauma a nd a subsequent cascade of cellular and molecular events that are term ed the secondary injury. Efforts aimed at improving neurologic outcome may depend on the manipulation of cellular and molecular mechanisms t hat are responsible for propagating this secondary injury cascade. Ast rocytes and TGF-beta are two potentially key components of this second ary injury. Methods. Twenty-one Sprague-Dawley adult rats underwent op en thoracic spinal cord injuries using the Allen weight-drop technique . Spinal cord specimens were harvested at 0, 1, 2, 4, 8, 24, and 72 ho urs after injury for histologic and immunohistochemical evaluation. Ha rvesting of injured and surrounding uninjured cord was performed befor e sectioning in sagittal and transverse planes. These paraffin-embedde d sections were stained with polyclonal antibodies against glial fibri llary acidic protein (GFAP, an astrocytic cytoskeleton marker) and TGF -beta1. Results. A complex astrocytic response to the spinal cord inju ry was found within 24 hours of injury. Both the geographic and tempor al pattens of astrocyte localization suggest a role in the regulation of spinal cord injury propagation. High concentrations of extracellula r TGF-beta were seen immediately after injury within the hematoma at t he zone of impact. Subsequently, intracellular TGF-beta was seen in as trocytic nuclei and cytoplasm, intramedullary and extramedullary capil lary endothelial cells, and in motor neurons. Conclusions. The neurolo gic outcome in patients with SCI results in part from a secondary inju ry whose cellular and molecular mechanisms are poorly understood. This study suggests that both astrocytes and TGF-beta are involved in the regulation of spinal cord secondary injury. An improved understanding of their specific roles may result in novel treatments to improve the outcome from SCI.