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Aprepitant Alleviates Poststroke Pneumonia in a Mouse Model of Middle Cerebral Artery Occlusion
Zhihui Xie1, Minghui Xin2, Fatao Yu1
1Department of Infectious Disease, Zibo Central Hospital, Zibo, People's Republic of China.
Abstract:
Elevated substance P can be utilized to predict early mortality during the first week of cerebral infarction. Whether aprepitant, a substance P receptor blocker could be utilized to alleviate poststroke pneumonia which is investigated in this study. Intraluminal monofilament model of middle cerebral artery occlusion (MCAO) was constructed in C57BL/6J male mice, and the relative expression of substance P was detected in collected bronchoalveolar lavage fluid (BALF) and lung tissue homogenate at 24 hours, 48 hours, and 72 hours poststroke. On the other hand, different concentrations of aprepitant (0.5, 1, and 2 mg/kg) were atomized and inhaled into MCAO mice. Inflammation cytokines and bacterial load were detected in collected BALF and lung tissue homogenate at 72-hour poststroke, and lung injury was revealed by histological examination. Aprepitant administration decreased total proteins, total cells, neutrophils, and macrophages in BALF. The concentrations of interleukin (IL)-6, IL-1β, tumor necrosis factor-α, interferon γ, monocyte chemoattractant protein-1, and IL-10 in lung tissue homogenates were also diminished by the administration of aprepitant. In conclusion, aprepitant could attenuate poststroke pneumonia in mice suggesting its potential therapeutic use in the clinic.
Insights
Aprepitant, a substance P receptor blocker, may alleviate poststroke pneumonia by reducing inflammation and bacterial load in mice. This finding suggests a potential clinical application for treating this common stroke complication.
Area of Science:
- Neuroscience
- Immunology
- Pharmacology
Background:
- Elevated substance P levels are linked to early mortality after cerebral infarction.
- Poststroke pneumonia is a significant complication following stroke.
- Substance P receptor antagonists may offer a therapeutic avenue.
Purpose of the Study:
- To investigate the efficacy of aprepitant, a substance P receptor blocker, in mitigating poststroke pneumonia.
- To evaluate the impact of aprepitant on inflammatory markers and bacterial load in a mouse model of stroke.
Main Methods:
- A middle cerebral artery occlusion (MCAO) model was established in male C57BL/6J mice.
- Substance P expression was measured in bronchoalveolar lavage fluid (BALF) and lung homogenates.
- Mice were treated with varying concentrations of inhaled aprepitant.
- Inflammatory cytokines, bacterial load, and lung injury were assessed post-treatment.
Main Results:
- Aprepitant administration significantly reduced total proteins, cells, neutrophils, and macrophages in BALF.
- Key inflammatory cytokines (IL-6, IL-1β, TNF-α, IFN-γ, MCP-1, IL-10) were decreased in lung tissue.
- Histological examination indicated reduced lung injury.
Conclusions:
- Aprepitant demonstrates a therapeutic potential in attenuating poststroke pneumonia in a mouse model.
- The findings support the investigation of aprepitant for clinical use in managing poststroke complications.
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