When replication teaches more than the original experiment--the saga of the unknown unknown

We recently published a description of the molecular mechanism involved in "progressive hemorrhagic necrosis", a pathological process that evolves during several hours after spinal cord injury, that is attributable to progressive capillary fragmentation, and that is due to upregulation and activation of SUR1-regulated channels in microvascular endothelium. In this commentary, we reflect on the independent replication of our original experiment by Dr. Phillip Popovich and colleagues, and how their initial attempt at replication led to the unexpected finding that anisotropy of spinal cord tissues strongly influences the patterns of both primary and secondary hemorrhage that are observed after impact injury to the spinal cord.