Argatroban is a synthetic thrombin inhibitor approved by U.S.Food and Drug Administration for the treatment of thrombosis.However,whether it plays a role in the repair of spinal cord injury is unknown.In this study,we...Argatroban is a synthetic thrombin inhibitor approved by U.S.Food and Drug Administration for the treatment of thrombosis.However,whether it plays a role in the repair of spinal cord injury is unknown.In this study,we established a rat model of T10 moderate spinal cord injury using an NYU Impactor ModerⅢand performed intraperitoneal injection of argatroban for 3 consecutive days.Our results showed that argatroban effectively promoted neurological function recovery after spinal cord injury and decreased thrombin expression and activity in the local injured spinal cord.RNA sequencing transcriptomic analysis revealed that the differentially expressed genes in the argatroban-treated group were enriched in the JAK2/STAT3 pathway,which is involved in astrogliosis and glial scar formation.Western blotting and immunofluorescence results showed that argatroban downregulated the expression of the thrombin receptor PAR1 in the injured spinal cord and the JAK2/STAT3 signal pathway.Argatroban also inhibited the activation and proliferation of astrocytes and reduced glial scar formation in the spinal cord.Taken together,these findings suggest that argatroban may inhibit astrogliosis by inhibiting the thrombin-mediated PAR1/JAK2/STAT3 signal pathway,thereby promoting the recovery of neurological function after spinal cord injury.展开更多
During natural viewing,we often recognize multiple objects,detect their motion,and select one object as the target to track.It remains to be determined how such behavior is guided by the integration of visual form and...During natural viewing,we often recognize multiple objects,detect their motion,and select one object as the target to track.It remains to be determined how such behavior is guided by the integration of visual form and motion perception.To address this,we studied how monkeys made a choice to track moving targets with different forms by smooth pursuit eye movements in a two-target task.We found that pursuit responses were biased toward the motion direction of a target with a hole.By computing the relative weighting,we found that the target with a hole exhibited a larger weight for vector computation.The global hole feature dominated other form properties.This dominance failed to account for changes in pursuit responses to a target with different forms moving singly.These findings suggest that the integration of visual form and motion perception can reshape the competition in sensorimotor networks to guide behavioral selection.展开更多
基金supported by the Key Project of the National Natural Science Foundation of China,No.81930070(to SF)the National Natural Science Foundation of China,No.81972074(to XY)the Key Program of Natural Science Foundation of Tianjin,No.19JCZDJC34900(to XY)。
文摘Argatroban is a synthetic thrombin inhibitor approved by U.S.Food and Drug Administration for the treatment of thrombosis.However,whether it plays a role in the repair of spinal cord injury is unknown.In this study,we established a rat model of T10 moderate spinal cord injury using an NYU Impactor ModerⅢand performed intraperitoneal injection of argatroban for 3 consecutive days.Our results showed that argatroban effectively promoted neurological function recovery after spinal cord injury and decreased thrombin expression and activity in the local injured spinal cord.RNA sequencing transcriptomic analysis revealed that the differentially expressed genes in the argatroban-treated group were enriched in the JAK2/STAT3 pathway,which is involved in astrogliosis and glial scar formation.Western blotting and immunofluorescence results showed that argatroban downregulated the expression of the thrombin receptor PAR1 in the injured spinal cord and the JAK2/STAT3 signal pathway.Argatroban also inhibited the activation and proliferation of astrocytes and reduced glial scar formation in the spinal cord.Taken together,these findings suggest that argatroban may inhibit astrogliosis by inhibiting the thrombin-mediated PAR1/JAK2/STAT3 signal pathway,thereby promoting the recovery of neurological function after spinal cord injury.
基金supported by the Beijing Natural Science Foundation(Z210009)the National Science and Technology Innovation 2030 Major Program(STI2030-Major Projects 2022ZD0204800)+1 种基金the National Natural Science Foundation of China(32070987,31722025,31730039)the Chinese Academy of Sciences Key Program of Frontier Sciences(QYZDB-SSW-SMC019).
文摘During natural viewing,we often recognize multiple objects,detect their motion,and select one object as the target to track.It remains to be determined how such behavior is guided by the integration of visual form and motion perception.To address this,we studied how monkeys made a choice to track moving targets with different forms by smooth pursuit eye movements in a two-target task.We found that pursuit responses were biased toward the motion direction of a target with a hole.By computing the relative weighting,we found that the target with a hole exhibited a larger weight for vector computation.The global hole feature dominated other form properties.This dominance failed to account for changes in pursuit responses to a target with different forms moving singly.These findings suggest that the integration of visual form and motion perception can reshape the competition in sensorimotor networks to guide behavioral selection.
