Traumatic spinal cord injury (SCI) initiates a plethora of biological responses that are collectively called the secondary injury cascade. Secondary injury responses are thought to be a major mediator of cell death and tissue destruction, both within and remote to the lesion epicenter. It is proposed that immunological and/or inflammatory mechanisms are a critical component in the secondary injury phenomenon. The broad objective of this proposal is to demonstrate that traumatic SCI initiates immunological responses that exacerbate the initial injury and worsen functional outcome. It is also proposed that inhibition of injury induced inflammation by the potent anti-inflammatory cytokine interleukin-10 will be neuroprotective. In this proposal we will use a weight drop apparatus (N.Y.U. Impactor) to induce spinal cord injury in rats. The neuropathology generated by this methodology is reproducible and well documented in the literature. However, the cellular and molecular mechanisms that are generated and ultimately result in: systemic inflammatory responses, infiltration of inflammatory cells into the spinal cord, tissue destruction and cell death are not well understood.
In specific aims 1 and 2 we propose to investigate the inflammatory responses initiated by traumatic SCI and determine how they mediate tissue destruction and cell death.
In Specific Aims 3 and 4 we propose to study the anti-inflammatory and neuroprotective effects of interleukin-10 in vitro and in vivo. Finally, in Aim 5 we are going to determine if traumatic SCI in humans initiates an inflammatory response. These studies will provide essential information about the immunological consequences of SCI. Furthermore, the results of these studies may aid in the development of novel therapeutic protocols for the treatment of SCI.
