Blocking ERK signaling pathway lowers MMP-9 expression to alleviate brain edema after traumatic brain injury in rats.
- Author:
Zhaohua TANG
1
;
Wentao WANG
2
;
Zili LIU
1
;
Xiaochuan SUN
1
;
Zhengbu LIAO
1
;
Feilan CHEN
1
;
Guangyuan JIANG
3
;
Gang HUO
1
Author Information
1. Department of Neurosurgery, First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China.
2. Department of Neurosurgery, Affiliated Hospital of Northwest University, Xi'an, 710018, China.
3. Department of Neurosurgery, Chongqing Traditional Chinese Medicine Hospital, Chongqing 400021, China.
- Publication Type:Journal Article
- MeSH:
Animals;
Brain Edema;
drug therapy;
etiology;
Brain Injuries, Traumatic;
complications;
drug therapy;
Gene Expression Regulation, Enzymologic;
drug effects;
Indazoles;
pharmacology;
therapeutic use;
MAP Kinase Signaling System;
drug effects;
Matrix Metalloproteinase 9;
genetics;
Piperazines;
pharmacology;
therapeutic use;
Protein Kinase Inhibitors;
pharmacology;
therapeutic use;
Random Allocation;
Rats;
Rats, Sprague-Dawley
- From:
Journal of Zhejiang University. Medical sciences
2020;40(7):1018-1022
- CountryChina
- Language:Chinese
-
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.
