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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
Journal of Zhejiang University. Medical sciences ; (6): 1018-1022, 2020.
Article in Chinese | WPRIM | ID: wpr-828505
ABSTRACT
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.
Subject(s)
Full text: Available Index: WPRIM (Western Pacific) Main subject: Pharmacology / Piperazines / Brain Edema / Random Allocation / Gene Expression Regulation, Enzymologic / Rats, Sprague-Dawley / Matrix Metalloproteinase 9 / MAP Kinase Signaling System / Therapeutic Uses / Protein Kinase Inhibitors Limits: Animals Language: Chinese Journal: Journal of Zhejiang University. Medical sciences Year: 2020 Type: Article

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Full text: Available Index: WPRIM (Western Pacific) Main subject: Pharmacology / Piperazines / Brain Edema / Random Allocation / Gene Expression Regulation, Enzymologic / Rats, Sprague-Dawley / Matrix Metalloproteinase 9 / MAP Kinase Signaling System / Therapeutic Uses / Protein Kinase Inhibitors Limits: Animals Language: Chinese Journal: Journal of Zhejiang University. Medical sciences Year: 2020 Type: Article