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Murine Aortic Crush Injury: An Efficient In Vivo Model of Smooth Muscle Cell Proliferation and Endothelial Function
Published on: June 11, 2017
Pharmacological neutropenia prevents endothelial dysfunction but not smooth muscle functions impairment induced by
Olivier Pétrault1, Thavarak Ouk, Sophie Gautier
1EA 1046-Laboratoire de Pharmacologie, Institut de Médecine Prédictive et de Recherche Thérapeutique, Université de Lille 2 et Centre Hospitalier Universitaire de Lille, 1 place de Verdun 59045, Lille Cedex, France.
Abstract:
1. The polymorphonuclear neutrophils (PMN) activation and mobilization observed in acute cerebral infarction contribute to the brain tissue damage, but PMN could also be involved in postischemic functional injury of ischemied blood vessel. 2. This study was undertaken to investigate whether pharmacological neutropenia could modify the postischemic endothelial dysfunction in comparison to smooth muscle whose impairment is likely more related to reperfusion and oxidative stress. 3. A cerebral ischemia-reperfusion by endoluminal occlusion of right middle cerebral artery (MCA) was performed 4 days after intravenous administration of vinblastine or 12 h after RP-3 anti-rat neutrophils monoclonal antibody (mAb RP-3) injection into the peritoneal cavity, on male Wistar rats with 1-h ischemia then followed by 24-h reperfusion period. Brain infarct volume was measured by histomorphometric analysis and vascular endothelial and smooth muscle reactivity of MCA was analysed using Halpern myograph. 4. Neutropenia induced a neuroprotective effect as demonstrated by a significant decrease of brain infarct size. In parallel to neuroprotection, neutropenia prevented postischemic impairment of endothelium-dependent relaxing response to acetylcholine. In contrast, smooth muscle functional alterations were not prevented by neutropenia. Ischemia-reperfusion-induced myogenic tone impairment remained unchanged in vinblastine and mAb RP-3-treated rats. Postischemic Kir2.x-dependent relaxation impairment was not prevented in neutropenic conditions. The fully relaxation of smooth muscle response to sodium nitroprusside was similar in all groups. 5. Our results evidenced the dissociate prevention of pharmacologically induced neutropenia on postischemic vascular endothelial and smooth muscle impairment. The selective endothelial protection by neutropenia is parallel to a neuroprotective effect suggesting a possible relationship between the two phenomena.
Insights
Pharmacological neutropenia, reducing white blood cells, protected brain tissue and blood vessel endothelium in rats after stroke. However, it did not improve smooth muscle function, suggesting a selective protective effect.
Area of Science:
- Neuroscience
- Vascular Biology
- Pharmacology
Background:
- Polymorphonuclear neutrophils (PMN) contribute to brain damage in acute cerebral infarction.
- PMN may also cause functional injury to blood vessels post-ischemia.
- Investigating pharmacological neutropenia's effect on endothelial vs. smooth muscle dysfunction is crucial.
Purpose of the Study:
- To determine if pharmacological neutropenia modifies post-ischemic endothelial dysfunction.
- To compare neutropenia's effect on endothelial dysfunction versus smooth muscle dysfunction.
- To explore the relationship between neuroprotection and endothelial protection by neutropenia.
Main Methods:
- Cerebral ischemia-reperfusion induced in rats via middle cerebral artery occlusion.
- Neutropenia achieved using vinblastine or anti-neutrophil antibody (mAb RP-3).
- Brain infarct volume assessed by histomorphometry; vascular reactivity measured using a myograph.
Main Results:
- Neutropenia significantly reduced brain infarct size, indicating a neuroprotective effect.
- Neutropenia prevented the impairment of endothelium-dependent relaxation.
- Smooth muscle function, including myogenic tone and Kir2.x-dependent relaxation, remained impaired.
Conclusions:
- Pharmacological neutropenia selectively protects the vascular endothelium, not smooth muscle, post-ischemia.
- The neuroprotective effect of neutropenia is associated with its endothelial protective action.
- These findings suggest a link between endothelial protection and reduced brain tissue damage in cerebral infarction.
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