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Expansion of the secondary injury following primary spinal cord injury is a major pathological event that increases damage to the spinal cord,for which effective treatments are desperately needed.Post-traumatic ischemia,resulting from tissue compression,thrombosis,and vasospasm,causes progressive neuronal death and is linearly related to the severity of injury.Our previous study demonstrated that there is an ischemic area at the front of the expanding secondary injury in the spinal cord in which two zones can be identified.In a zone proximal to the lesion site,most of the neurons have disappeared.In a distal zone,there is also clear evidence of ischemia,though the morphology of the neurons appears largely normal.We hypothesized that enhancement of blood circulation in the spinal cord may be helpful for recovery,and indeed,we demonstrated that a traditional Chinese medicine,shu-xue-tong,effectively reduces the secondary injury.In the present study,we further investigated the use of innate blood-borne factor fibrinogen,which is a 340 kDa protein secreted by hepatocytes and is present at high concentration in the blood.Upon activation of the coagulation cascade,both the a and p chains of fibrinogen are cleaved by thrombin to form fibrin polymer.This polymer,by interacting with platelets,accomplishes the process of blood clotting.Furthermore,recent studies reported that fibrinogen leaking from ruptured blood vessels triggers the activation of astrocytes and microglia,suggesting its involvement in the development of secondary spinal cord injury.Batroxobin is a thrombin-like serine that has been successfully used in various ischemic disorders,such as stroke,deep-vein thrombosis,myocardial infarction,peripheral arterial thrombosis,and sudden deafness.In contrast to thrombin,batroxobin only cleaves the a chain of fibrinogen,resulting in the production of a fibrin monomer,which has poorer cross-linking ability than the polymer,and thus decreases the blood fibrinogen concentration and promotes blood flow.Its effect on spinal cord injury,however,has not been studied.Given the important role fibrinogen plays in the pathology of spinal cord injury,the aim of the present study was to determine the effect of reducing fibrinogen with batroxobin in rats with spinal cord contusion.A rat spinal cord contusion model was made at the T8 level.Two BU/kg of batroxobin was initially administered via the tail vein at 12 hours,with two additional injections at 3 and 5 days after spinal cord injury.Two hours after the last dose of batroxobin,blood samples were collected for coagulation testing.Spinal cord blood flow was measured 2 hours after the last batroxobin dose using a laser-Doppler flow-meter.The Basso,Beattie,and Bresnahan scoring,rump-height index assay,and footprint analysis were used to evaluate locomotion at 1 day before,and 1,4,and 7 days after spinal cord injury.Immunohistochemistry of neuronal nuclei,glial fibrillary acidic protein,neurocan,and ionized calcium-binding adapter molecule-1 were performed to assess the neuronal survival and glial reaction at 7 days after spinal cord injury.We found that 2 BU/kg batroxobin effectively decreased the plasma fibrinogen concentration,significantly increased spinal blood flow,enhanced neuronal survival,mitigated astrocyte and microglia activation,and improved locomotion.These data suggest that batroxobin has multiple beneficial effects on spinal cord injury,indicating a potential clinical application.(Neurosci Bull.2013 Aug;29(4):501-8).