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Author Spotlight: Establishing a Reliable Distal MCA Occlusion Model in Mice for Stroke Research
Published on: December 15, 2023
Temporal alteration of microglia to microinfarcts in rat brain induced by the vascular occlusion with fluorescent
Yi Shen1, Jingjing Cui1, Shuang Zhang2
1Institute of Acupuncture and Moxibustion, China Academy of Chinese Medical Sciences, Beijing, China.
Abstract:
Microglia, the resident immune cells in the central nervous system, can monitor the microenvironment and actively respond to ischemic stroke and other brain injuries. In this procedure, microglia and neurons can cross-talk via transmembrane chemokine, Fractalkine (CX3CL1), to impact one another. We used a rat model of multifocal microinfarcts induced by the injection of fluorescent microspheres into the right common carotid artery and examined the morphological alteration of blood vessels, microglia, astrocytes, and neurons at 6 h, 1, 7, and 14 days after modeling, along with neurobehavioral tests and the staining of CX3CL1 in this study. Our results demonstrated that in the infarcted regions, astrocytes and microglia activated in response to neuronal degeneration and upregulation of cleaved caspase-3, which occurred concurrently with vascular alteration and higher expression of CX3CL1. We provided sequential histological data to shed light on the morphological changes after modeling, which would help in the identification of new targets and the choice of the ideal time window for therapeutic intervention in ischemic stroke.
Insights
Microglia and astrocytes activate following ischemic stroke, interacting with neurons via Fractalkine (CX3CL1). This study details the cellular and vascular changes in a rat stroke model, identifying potential therapeutic targets.
Area of Science:
- Neuroscience
- Immunology
- Pathology
Background:
- Microglia are key immune cells in the central nervous system, responding to injury.
- Neuronal and microglial interactions, particularly via Fractalkine (CX3CL1), are crucial in brain injury.
- Ischemic stroke triggers complex cellular responses within the brain microenvironment.
Purpose of the Study:
- To investigate the dynamic morphological and cellular changes in a rat model of multifocal microinfarcts.
- To examine the role of microglia, astrocytes, neurons, and vascular alterations post-ischemic stroke.
- To correlate these changes with Fractalkine (CX3CL1) expression and neurobehavioral outcomes.
Main Methods:
- Induction of multifocal microinfarcts in rats using fluorescent microspheres.
- Histological analysis of blood vessels, microglia, astrocytes, and neurons at multiple time points (6 h, 1, 7, 14 days).
- Neurobehavioral testing and immunohistochemical staining for CX3CL1 and cleaved caspase-3.
Main Results:
- Activated microglia and astrocytes were observed in infarcted regions, correlating with neuronal degeneration.
- Upregulation of cleaved caspase-3 indicated apoptotic processes.
- Vascular alterations and increased CX3CL1 expression were concurrent with cellular changes.
Conclusions:
- The study provides sequential histological data illustrating morphological changes after ischemic stroke induction.
- Findings highlight the dynamic interplay between immune cells, neurons, and vasculature.
- The results may aid in identifying therapeutic targets and optimal intervention windows for ischemic stroke.
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