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Updated: Sep 21, 2025
A Preclinical Controlled Cortical Impact Model for Traumatic Hemorrhage Contusion and Neuroinflammation
Published on: June 10, 2020
[Effects of MCC950 on nerve injury in rats with intracerebral hemorrhage]
Ya-Jing Guo1, Jing Ren1, Han Liu1
1Hebei University of Chinese Medicine, Shijiazhuang 050200, China.
Abstract:
Objective: To investigate the effects of the pyrin domain-containing protein 3 (NLRP3) inflammasome inhibitor MCC950 on nerve injury in rats with intracerebral hemorrhage(ICH). Methods: Seventy-two SD rats were randomly divided into three groups (n=24): Sham group, ICH group and MCC950 group. ICH group and MCC950 group rats were injected with autogenous non-anticoagulant blood to establish ICH model, and then the rats in MCC950 group were intraperitoneally injected with MCC950 at the dose of 10 mg/kg(2 mg/ml) for 3 days after ICH model was established. Seventy-two hours after the establishment of the model, the forelimb placement test, the corner test and mNSS score were performed to observe the neurological function of the rats with ICH. The volume of hematoma was observed in fresh brain tissue sections. HE staining was used to observe the pathological changes of brain tissue. The dry-wet weight ratio was calculated to evaluate the changes of brain tissue edema. The degeneration of neurons was observed by FJC staining. The neuronal apoptosis was observed by TUNEL staining. The protein expression and activation levels of NLRP3, ASC, caspase-1, IL-1β, IL-18 and GSDMD were determined by Western blot. Results: Compared with sham group, the percentage of successful placement of left forelimb and left turn was decreased significantly (P＜0.01, P＜0.05), mNSS score was increased significantly (P＜0.01) in ICH group. Hematoma volume was increased significantly, the number of microglial cells around the hematoma was increased, the number of neurons was decreased, nerve cell swelled, some cells showed pyknotic necrosis, and the staining was deepened. The water content of the right base was increased significantly (P＜0.05). The number of FJC positive and TUNEL positive cells around the hematoma was increased significantly (P＜0.05). The levels of NLRP3, ASC, caspase-1, pro-caspase-1, caspase-1/pro-caspase-1 ratio, GSDMD-N, GSDMD, GSDMD-N/GSDMD ratio, IL-1β and IL-18 were increased significantly (P＜0.01, P＜ 0.05). Compared with ICH group, the percentage of successful placement of left forelimb and left turn was increased significantly in MCC950 group (P＜0.05), while the mNSS score and the volume of hematoma were decreased significantly (P＜0.01), the swelling degree of nerve cells around the hematoma was reduced significantly, and the number of pyrotic necrotic cells was decreased. The water content of the right base was decreased significantly (P＜0.05), and the number of FJC positive and TUNEL positive cells around the hematoma was decreased significantly (P＜0.05). The levels of NLRP3, ASC, caspase-1, pro-caspase-1, caspase-1/pro-caspase-1 ratio, GSDMD-N, GSDMD, GSDMD-N/GSDMD ratio, IL-1β and IL-18 were decreased significantly (P＜0.05). Conclusion: MCC950 can ameliorate nerve injury after ICH by inhibiting NLRP3 inflammasome mediated inflammation and pyroptosis.
Insights
The NLRP3 inflammasome inhibitor MCC950 reduces nerve injury and inflammation in rats after intracerebral hemorrhage (ICH). MCC950 treatment improved neurological function and decreased brain damage by inhibiting NLRP3 inflammasome-mediated pyroptosis.
Area of Science:
- Neuroscience
- Immunology
- Pharmacology
Background:
- Intracerebral hemorrhage (ICH) is a severe neurological condition often leading to significant nerve injury.
- The NLRP3 inflammasome plays a critical role in inflammatory responses following ICH.
- Targeting the NLRP3 inflammasome presents a potential therapeutic strategy for mitigating ICH-induced damage.
Purpose of the Study:
- To evaluate the therapeutic effects of the NLRP3 inflammasome inhibitor MCC950 on nerve injury in a rat model of ICH.
- To investigate the impact of MCC950 on NLRP3 inflammasome activation, inflammation, and pyroptosis after ICH.
Main Methods:
- An ICH model was established in Sprague-Dawley rats by injecting autologous blood.
- Rats were treated with MCC950 (10 mg/kg) or vehicle, and neurological function was assessed using behavioral tests (forelimb placement, corner test, mNSS).
- Brain tissue was analyzed for hematoma volume, edema (dry-wet weight ratio), neuronal degeneration (FJC staining), apoptosis (TUNEL staining), and protein expression of NLRP3 inflammasome components (Western blot).
Main Results:
- ICH significantly impaired neurological function, increased hematoma volume, brain edema, neuronal degeneration, and apoptosis compared to sham controls.
- ICH induced significant upregulation of NLRP3 inflammasome components (NLRP3, ASC, caspase-1, IL-1β, IL-18, GSDMD).
- MCC950 treatment significantly improved neurological function, reduced hematoma volume and brain edema, and decreased neuronal injury and apoptosis. MCC950 also suppressed the activation of the NLRP3 inflammasome pathway.
Conclusions:
- MCC950 demonstrates significant neuroprotective effects in a rat model of ICH.
- Inhibition of the NLRP3 inflammasome pathway by MCC950 ameliorates nerve injury, inflammation, and pyroptosis following ICH.
- Targeting NLRP3 inflammasome with MCC950 is a promising therapeutic approach for managing intracerebral hemorrhage.
