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[Blocking p38 signal pathway lowers MMP-9 expression and reduces brain edema in rats with traumatic brain injury]
Zhaohua Tang1, Zhengbu Liao, Quanhong Shi
1Department of Neurosurgery, First Affiliated Hospital of Chongqing Medical University, China. ducker-1@hotmail.com
Objective:
To explore the role of p38 signal pathway in regulating matrix metalloproteinase-9 (MMP-9) expression and brain edema formation in a rat model of traumatic brain injury (TBI).
Methods:
A total of 130 adult male Sprague Dawley rats were randomly divided into 4 groups, namely the normal group (n=10), sham-operated group (n=40), TBI (induced by Feeney free falling methods) group (n=40), and SB group with intraperitoneal SB203580 treatment (10 µmol/L) 15 min before TBI (n=40). The rats were sacrificed 2 h and 2 days after TBI. The expressions of p38, p-p38, and MMP-9 mRNA and protein were detected by RT-PCR and Western blotting. The blood brain barrier permeability was detected by Evans Blue (EB) test, and the brain water content (BWC) was determined using a gravimetric technique.
Results:
The expression of p-p38 protein increased markedly 2 h after TBI (P<0.05), and was suppressed by SB203580 treatment (P<0.05). MMP-9 mRNA and protein showed no obvious increase at 2 h after TBI, but significantly increased at 2 days as compared with those in the sham-operated group (P<0.05). MMP-9 mRNA and protein were much lower in SB group than in TBI group 2 days after TBI (P<0.05). The blood brain barrier permeability significantly increased 2 h after TBI (P<0.05) and kept increasing until 2 days (P<0.05), but was reduced significantly by SB203580 (P<0.05). BWC increased obviously 2 days after TBI (P<0.05) and was lessened by SB203580 (P<0.05).
Conclusion:
Blocking p38 signal pathway can attenuate MMP-9 upregulation and brain edema after TBI, suggesting the important role of p38 in regulating MMP-9 expression to affect traumatic brain edema.
Insights
Blocking the p38 signal pathway reduces matrix metalloproteinase-9 (MMP-9) upregulation and brain edema following traumatic brain injury (TBI). This highlights p38
Area of Science:
- Neuroscience
- Molecular Biology
- Pathophysiology
Background:
- Traumatic brain injury (TBI) is a significant cause of mortality and disability.
- Brain edema and blood-brain barrier (BBB) disruption are critical complications following TBI.
- The role of the p38 signal pathway and matrix metalloproteinase-9 (MMP-9) in TBI pathogenesis requires further elucidation.
Purpose of the Study:
- To investigate the involvement of the p38 signal pathway in regulating MMP-9 expression and brain edema formation in a rat model of TBI.
- To determine the therapeutic potential of inhibiting the p38 pathway in TBI.
Main Methods:
- Adult male Sprague Dawley rats were subjected to TBI using the Feeney free falling method.
- Groups included normal, sham-operated, TBI, and TBI with SB203580 (p38 inhibitor) treatment.
- MMP-9 and p38 pathway activation (p-p38) were assessed via RT-PCR and Western blotting.
- Blood-brain barrier permeability and brain water content were quantified.
Main Results:
- TBI induced significant p38 pathway activation and increased blood-brain barrier permeability within 2 hours.
- MMP-9 expression and brain edema formation were significantly elevated at 2 days post-TBI.
- SB203580 treatment effectively suppressed p38 activation, reduced MMP-9 upregulation, and attenuated BBB disruption and brain edema.
Conclusions:
- The p38 signal pathway plays a crucial role in mediating MMP-9 upregulation and subsequent brain edema following TBI.
- Inhibition of the p38 pathway demonstrates a promising therapeutic strategy for mitigating TBI-induced brain edema and secondary injury.
