The role of hemorrhage following spinal-cord injury

• Injection of collagenase leads to BSCB breakdown and ongoing intraspinal hemorrhage.
• This is sufficient to recruit leukocytes and also to damage axons and neurons.
• The damage leads to locomotor deficiency and loss of weight.
• Injection of collagenase into the spinal cord is a simple and reproducible model.

Spinal-cord injury is characterized by primary damage as a direct consequence of mechanical insult, and secondary damage that is partly due to the acute inflammatory response. The extent of any hemorrhage within the injured cord is also known to be associated with the formation of intraparenchymal cavities and has been anecdotally linked to secondary damage. This study was designed to examine the contribution of blood components to the outcome of spinal-cord injury. We stereotaxically microinjected collagenase, which causes localized bleeding, into the spinal cord to model the hemorrhage associated with spinal cord injury in the absence of significant mechanical trauma. Tissue damage was observed at the collagenase injection site over time, and was associated with localized disruption of the blood-spinal-cord barrier, neuronal cell death, and the recruitment of leukocytes. The magnitude of the bleed was related to neutrophil mobilization. Interestingly, the collagenase-induced injury also provoked extended axonal damage. With this model, the down-stream effects of hemorrhage are easily discernible, and the impact of treatment strategies for spinal-cord injury on hemorrhage-related injury can be evaluated.