Post-ischemia common carotid artery occlusion worsens memory loss, but not sensorimotor deficits, in long-term
Zhong Yang1, Xuan Li2, Zhipeng Cao3
1Multidisciplinary Neuroprotection Laboratories, Center of Perioperative Organ Protection, Department of Anesthesiology, Duke University Medical Center, Durham, NC 27710, USA; Department of Orthopedics, The Fifth Central Hospital of Tianjin, Tanggu District, Tianjin 300450, China.
Abstract:
Ischemic stroke in rodents is usually induced by intraluminal occlusion of the middle cerebral artery (MCA) via the external carotid artery (ECA) or the common carotid artery (CCA). The latter route requires permanent CCA occlusion after ischemia, and here, we assess its effects on long-term outcomes. Transient occlusion of MCA and CCA was performed at normal body temperature. After 90 min of ischemia, mice were randomized to permanent CCA occlusion or no occlusion (control group). Body weight, and motor and sensory functions, ie, pole test, adhesive tape removal, and elevated plus maze, were evaluated at 24 h, and at 7 and 28 days after stroke. Infarct volume, apoptosis, and activation of astrocytes and microglia were assessed at 4 weeks by an investigator blinded to groups. The Morris water maze test was performed at 3 weeks in the second experiment. One mouse died at 4 days, and the other mice survived with persistent neurologic deficits. CCA-occluded mice exhibited delayed turn on the pole at 24 h and decreased responses to the von Frey filament, and spent more time on the pole at 7 and 28 days than the control group. Infarction, hemispheric atrophy, glial activation, and apoptotic neuronal death were present in all mice, and no intra-group difference was found. However, CCA-occluded mice had a significantly poorer performance in the Morris water maze compared to the control group, which showed an adverse effect of post-ischemia CCA occlusion on cognition. Thus, the model selection should be well considered in preclinical efficacy studies on stroke-induced vascular dementia and stroke with Alzheimer's disease.
Insights
Permanent common carotid artery (CCA) occlusion after transient middle cerebral artery (MCA) occlusion in rodents impairs long-term cognitive function. This finding is crucial for selecting appropriate stroke models in preclinical research.
Area of Science:
- Neuroscience
- Pathology
- Animal Models
Background:
- Ischemic stroke models in rodents commonly use middle cerebral artery (MCA) occlusion.
- Occlusion can be transient or permanent, with varying effects on long-term outcomes.
- The impact of permanent common carotid artery (CCA) occlusion post-ischemia is not fully understood.
Purpose of the Study:
- To evaluate the long-term effects of permanent CCA occlusion following transient MCA occlusion in a rodent stroke model.
- To assess the influence of this procedural variation on neurological deficits, cognitive function, and neuropathology.
Main Methods:
- Rodents underwent transient MCA and CCA occlusion followed by randomization to permanent CCA occlusion or no occlusion (control).
- Motor and sensory functions were assessed using pole, adhesive tape removal, and elevated plus maze tests.
- Infarct volume, apoptosis, and glial activation were evaluated; cognitive function was assessed using the Morris water maze.
Main Results:
- CCA-occluded mice showed delayed motor responses and altered sensory function compared to controls.
- While infarct volume and neuropathology were similar, CCA-occluded mice exhibited significantly poorer performance in the Morris water maze.
- This indicates an adverse effect of post-ischemia CCA occlusion on cognitive outcomes.
Conclusions:
- Permanent CCA occlusion following transient MCA occlusion in rodents adversely affects long-term cognitive function.
- Model selection is critical for preclinical studies investigating stroke-induced vascular dementia and stroke with Alzheimer's disease.
- Researchers should carefully consider the implications of CCA occlusion on cognitive outcomes in stroke model selection.
