Precision in Spinal Cord Injury Research: A Novel Electromagnetic Impactor for a Consistent Porcine Model.

Purpose: Replicating spinal cord injury (SCI) in large animals is necessary for evaluating translational therapeutics, yet there is currently no commercial, standardized device for inducing SCI. We present the fabrication and testing of a custom impactor device for producing repeatable contusion SCI in porcine models.

Methods: The device was built, and mechanical modeling was utilized for calibration.

A vicious cycle involving release of heat shock protein 60 from injured cells and activation of toll-like receptor 4 mediates neurodegeneration in the CNS.

Infection, ischemia, trauma, and neoplasia elicit a similar inflammatory response in the CNS characterized by activation of microglia, the resident CNS monocyte. The molecular events leading from CNS injury to the activation of innate immunity is not well understood. We show here that the intracellular chaperone heat shock protein 60 (HSP60) serves as a signal of CNS injury by activating microglia through a toll-like receptor 4 (TLR4)-dependent and myeloid differentiation factor 88 (MyD88)-dependent pathway.

TLR2 and caspase-8 are essential for group B Streptococcus-induced apoptosis in microglia.

Microglia, the resident innate immune cells of the CNS, detect invading pathogens via various receptors, including the TLR. Microglia are involved in a number of neurodegenerative diseases in which their activation may be detrimental to neurons. It is largely unknown how this potentially deleterious action can be countered on a cellular level.

Toll-like receptor 2 mediates CNS injury in focal cerebral ischemia.

Toll-like receptors (TLR) recognize molecular structures associated with pathogens as well as host-derived components and initiate an inflammatory innate immune response. Microglia represent the resident immune host defense and are the major inflammatory cell type in the central nervous system (CNS). We show here that TLR2-deficient mice develop a decreased CNS injury compared to wild type mice in a model of focal cerebral ischemia.