Progesterone Promotes Axonal Regeneration After Cerebral Hemorrhage And Related Mechanisms

ObjectiveTo observe the effects of progesterone on axon regeneration in the basal ganglia of the brain after intracerebral hemorrhage(ICH),and to explore its specific mechanism.Methods1.Rats were divided into cerebral hemorrhage group,progesterone low dose group(8 mg/kg),progesterone high dose group(16 mg/kg),and sham operation group as control group.The neurological deficits,brain water content and pathological changes were observed at 1,3,7 and 14 days after operation.2.Analysis of cerebral hematoma volume,oxidative stress related indicators and apoptosis related indicators in each group at 3 days after operation.3.Western blot was used to observe the expression changes of axon growth-related proteins at 1,3,7 and 14 days after operation.Immunohistochemistry and immunofluorescence were used to detect changes in axon growth-related protein expression 3 days after surgery.4.Western blot analysis showed that the expression of GAP43,NF200 and P-Akt was down-regulated and the expression of MAG,Nogo-A and RhoA was increased in the inhibitor group compared with the large and low-dose progesterone groups5.Double-labeled fluorescence results showed that each protein was expressed on the same kind of cells,and the expression of P-Akt in neuronal cells increased and the expression of RhoA decreased in the high-dose progesterone group compared with the cerebral hemorrhage group.Results1.Progesterone can significantly improve neurological dysfunction and reduce brain edema after cerebral hemorrhage in rats.Among them,the rats had the most severe neurological deficits and the highest water content in brain tissue at 3 days.HE staining showed that progesterone can improve brain tissue damage after cerebral hemorrhage at various time points2.The cerebral hematoma volume was the largest in the cerebral hemorrhage group,and apoptosis related indicators,the oxidative stress product level was the most obvious.The damage was relieved at various time points after progesterone intervention.The effect of the high dose group was more obvious than the low dose group3.Western blot,immunohistochemistry and immunofluorescence showed that the expression of GAP43 and NF200 was increased and the expression of MAG and Nogo-A was decreased in the high-dose progesterone group compared with the low-dose progesterone group and cerebral hemorrhage group.4.Western blot analysis showed that the expression of GAP43,NF200 and P-Akt was down-regulated and the expression of MAG,Nogo-A and RhoA was increased in the inhibitor group compared with the large and low-dose progesterone groups.5.Double-labeled fluorescence results showed that each protein was expressed on the same kind of cells,and the expression of P-Akt in neuronal cells increased and the expression of RhoA decreased in the high-dose progesterone group compared with the cerebral hemorrhage group.ConclusionProgesterone can improve neurological dysfunction after cerebral hemorrhage and promote regeneration and repair of injured axons,which may be related to activation of PI3K/Akt pathway and inhibition of RhoA expression.