Blocking ERK signaling pathway lowers MMP-9 expression to alleviate brain edema after traumatic brain injury in rats / 南方医科大学学报

OBJECTIVE@#To investigate the effects of blocking the activation of ERK pathway on the expression of matrix metalloproteinase-9 (MMP-9) and the formation of cerebral edema in SD rats after brain injury.@*METHODS@#Ninety SD rats were randomly divided into 3 equal groups, including a sham-operated group, modified Feeney's traumatic brain injury model group, and ERK inhibition group where the ERK inhibitor SCH772984 (500 μg/kg) was injected via the femoral vein 15 min before brain trauma. At 2 h and 2 days after brain trauma, the permeability of blood-brain barrier was assessed by Evans blue method, the water content of the brain tissue was determined, and the phosphorylation level of ERK and the expression level of MMP-9 mRNA and protein were measured by RT-PCR and Western blotting.@*RESULTS@#Compared with the sham-operated group, the rats with brain trauma exhibited significantly increased level of ERK phosphorylation at 2 h and significantly increased expression of MMP-9 mRNA and protein 2 days after the injury ( < 0.01). Treatment with the ERK inhibitor significantly decreased the phosphorylation level of ERK after the injury ( < 0.01), suppressed over-expression of MMP-9 mRNA and protein 2 days after the injury ( < 0.01). The permeability of blood-brain barrier increased significantly 2 h after brain trauma ( < 0.05) and increased further at 2 days ( < 0.01); the water content of the brain did not change significantly at 2 h ( > 0.05) but increased significantly 2 d after the injury ( < 0.01). Treatment with the ERK inhibitor significantly lowered the permeability of blood-brain barrier and brain water content after brain trauma ( < 0.01).@*CONCLUSIONS@#Blocking the activation of ERK pathway significantly reduced the over-expression of MMP-9 and alleviates the damage of blood-brain barrier and traumatic brain edema, suggesting that ERK signaling pathway plays an important role in traumatic brain edema by regulating the expression of MMP-9.

Blocking ERK signaling pathway lowers MMP-9 expression to alleviate brain edema after traumatic brain injury in rats / 浙江大学学报·医学版

OBJECTIVE@#To investigate the effects of blocking the activation of ERK pathway on the expression of matrix metalloproteinase-9 (MMP-9) and the formation of cerebral edema in SD rats after brain injury.@*METHODS@#Ninety SD rats were randomly divided into 3 equal groups, including a sham-operated group, modified Feeney's traumatic brain injury model group, and ERK inhibition group where the ERK inhibitor SCH772984 (500 μg/kg) was injected via the femoral vein 15 min before brain trauma. At 2 h and 2 days after brain trauma, the permeability of blood-brain barrier was assessed by Evans blue method, the water content of the brain tissue was determined, and the phosphorylation level of ERK and the expression level of MMP-9 mRNA and protein were measured by RT-PCR and Western blotting.@*RESULTS@#Compared with the sham-operated group, the rats with brain trauma exhibited significantly increased level of ERK phosphorylation at 2 h and significantly increased expression of MMP-9 mRNA and protein 2 days after the injury ( < 0.01). Treatment with the ERK inhibitor significantly decreased the phosphorylation level of ERK after the injury ( < 0.01), suppressed over-expression of MMP-9 mRNA and protein 2 days after the injury ( < 0.01). The permeability of blood-brain barrier increased significantly 2 h after brain trauma ( < 0.05) and increased further at 2 days ( < 0.01); the water content of the brain did not change significantly at 2 h ( > 0.05) but increased significantly 2 d after the injury ( < 0.01). Treatment with the ERK inhibitor significantly lowered the permeability of blood-brain barrier and brain water content after brain trauma ( < 0.01).@*CONCLUSIONS@#Blocking the activation of ERK pathway significantly reduced the over-expression of MMP-9 and alleviates the damage of blood-brain barrier and traumatic brain edema, suggesting that ERK signaling pathway plays an important role in traumatic brain edema by regulating the expression of MMP-9.

Research Progress of Trx/TXNIP in Stroke / 现代生物医学进展

Cerebral apoplexy is one of the main causes of death in the middle-aged and elderly population,which has higher mortality and disability rate.The incidence of the disease is increasing year by year and it is a serious threat to human life and health.Therefore,it is of great significance to find an effective target for the diagnosis and treatment of stroke.Thioredoxin (Trx) is the major thiol reducing agent in the cells,it is involved in many signal transduction pathways in the cells by regulating the redox state of the cell.It has disulphide reductase activity,which can reduce the oxidative stress injury in the rats after the stroke.Thioredoxin interacting protein (TXNIP) is an endogenous inhibitor of Trx,it can destroy the redox balance and promote the oxidative stress by binding/inhibiting the activity of Trx,while the inhibition or knockdown of TXNIP has obvious neuroprotective effects.Recent studies suggest that Trx/TXNIP may be involved in the pathophysiology of cerebral apoplexy by a variety of pathways.This article analyses the research status of Trx/TXNIP and studies the localization of Trx system in the central nervous system and the progress of Trx system in ischemic cerebral apoplexy.It reviews the mechanism of Trx/TXNIP in cerebral apoplexy and prospectes the signaling pathways involved in the pathophysiological process of Trx/TXNIP to provide new ideas for the treatment of cerebral apoplexy.

Effects of Embolization and Clipping Therapy on Cognitive Function in Patients with Intracranial Aneurysms / 现代生物医学进展

Objective:To evaluate the effects of endovascular embolization and microsurgical clipping on cognitive function in patients with intracranial aneurysm.Methods:A total of 80 patients with intracranial aneurysms,who were treated in Chongqing Hospital of Traditional Chinese Medicine from March 2014 to September 2015,were selected and randomly divided into control group(n=40) and experimental group (n=40).The control group was treated with microsurgical clipping,and the experimental group,with endovascular embolization.The postoperative cognitive function was assessed by the mini mental state examination scale (MMSE),and length of stay,in-hospital mortality rate,mortality rate in 1 year and the incidence of postoperative adverse reactions were compared between the two groups.Results:The total score (26.78± 0.85) of MMSE in the experimental group was higher than that (22.25± 0.63) of the control group (P＜0.05).The cognitive dysfunction rate (37.50％) of the experimental group was lower than that (55.00％) of the control group (P＜0.05).The length of stay [(6.7± 3.9) days] of the experimental group was lower than that [(9.6± 4.5) days] of the control group(P＜0.05).There were no significant differences in in-hospital mortality rate and mortality rate in 1 year,and the incidence of adverse reactions between the two groups (P＞0.05).Conclusion:Endovascular interventional therapy can improve the cognitive function of the patients with intracranial aneurysms and shorten the length of hospital stay.