Mouse Model of Middle Cerebral Artery Occlusion

Chiang, Terrance; Messing, Robert O.; Chou, Wen‐Hai

doi:10.3791/2761-v

Cited by 29 publications

(17 citation statements)

References 4 publications

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“…Male BALB/c mice, 8 weeks old, were utilized for MCAO following the standard procedure . The occlusion was sustained for 1 h prior to reperfusion.…”

Section: Methodsmentioning

confidence: 99%

Observing Extracellular Vesicles Originating from Endothelial Cells in Vivo Demonstrates Improved Astrocyte Function Following Ischemic Stroke via Aggregation-Induced Emission Luminogens

et al. 2023

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Extracellular vesicles (EVs) obtained from endothelial cells (ECs) have significant therapeutic potential in the clinical management of individuals with ischemic stroke (IS) because they effectively treat ischemic stroke in animal models. However, because molecular probes with both high labeling efficiency and tracer stability are lacking, monitoring the actions of EC-EVs in the brain remains difficult. The specific intracellular targets in the brain that EC-EVs act on to produce their protective effects are still unknown, greatly impeding their use in clinical settings. For this research, we created a probe that possessed aggregation-induced emission (AIE) traits (namely, TTCP), enabling the effective labeling of EC-EVs while preserving their physiological properties. In vitro, TTCP simultaneously had a higher EC-EV labeling efficiency and better tracer stability than the commercial EV tags PKH-67 and DiI. In vivo, TTCP precisely tracked the actions of EC-EVs in a mouse IS model without influencing their protective effects. Furthermore, through the utilization of TTCP, it was determined that astrocytes were the specific cells affected by EC-EVs and that EC-EVs exhibited a safeguarding impact on astrocytes following cerebral ischemia-reperfusion (I/R) injury. These protective effects encompassed the reduction of the inflammatory reaction and apoptosis as well as the enhancement of cell proliferation. Further analysis showed that miRNA-155-5p carried by EC-EVs is responsible for these protective effects via regulation of the c-Fos/AP-1 pathway; this information provided a strategy for IS therapy. In conclusion, TTCP has a high EC-EV labeling efficiency and favorable in vivo tracer stability during IS therapy. Moreover, EC-EVs are absorbed by astrocytes during cerebral I/R injury and promote the restoration of neurological function through the regulation of the c-Fos/AP-1 signaling pathway.

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“…Male BALB/c mice, 8 weeks old, were utilized for MCAO following the standard procedure . The occlusion was sustained for 1 h prior to reperfusion.…”

Section: Methodsmentioning

confidence: 99%

Observing Extracellular Vesicles Originating from Endothelial Cells in Vivo Demonstrates Improved Astrocyte Function Following Ischemic Stroke via Aggregation-Induced Emission Luminogens

et al. 2023

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“…This procedure has been shown as high reproducibility, with big infarction areas and reperfusion of the brain achieved by extracting the filament out of the body. [ 183 ] The same carotid arteries were blocked using a different strategy. Blood was extracted from a rabbit and mixed with bovine thrombin to form clots of around 2.7 mm in size.…”

Section: Models Used For Validating Mechanoresponsive Ddsmentioning

confidence: 99%

Mechanoresponsive Drug Delivery Systems for Vascular Diseases

Navarro

Lomora

2023

Macromolecular Bioscience

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Mechanoresponsive drug delivery systems (DDS) have emerged as promising candidates to improve the current effectiveness and lower the side effects typically associated with direct drug administration in the context of vascular diseases. Despite tremendous research efforts to date, designing drug delivery systems able to respond to mechanical stimuli to potentially treat these diseases is still in its infancy. By understanding relevant biological forces emerging in healthy and pathological vascular endothelium, it is believed that better‐informed design strategies can be deduced for the fabrication of simple‐to‐complex macromolecular assemblies capable of sensing mechanical forces. These responsive systems are discussed through insights into essential parameter design (composition, size, shape, and aggregation state) , as well as their functionalization with (macro)molecules that are intrinsically mechanoresponsive (e.g., mechanosensitive ion channels and mechanophores). Mechanical forces, including the pathological shear stress and exogenous stimuli (e.g., ultrasound, magnetic fields), used for the activation of mechanoresponsive DDS are also introduced, followed by in vitro and in vivo experimental models used to investigate and validate such novel therapies. Overall, this review aims to propose a fresh perspective through identified challenges and proposed solutions that could be of benefit for the further development of this exciting field.

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“…To establish the MCAO model, a silicon-coated monofilament (403756PK5Re; Doccol, Sharon, MA, USA) was inserted for external carotid artery embolization, and then removed to allow reperfusion. 22,23 During the surgery, a flexible fiber probe linked to a MoorLDL-HR laser Doppler flowmeter (Moor Instruments, UK) was used to monitor and confirm successful MCAO and reperfusion. The neck incisions were then sutured, and rats were returned to their cages and given free access to food and water.…”

Section: Establishment Of the Mcao Rat Modelmentioning

confidence: 99%

Electroacupuncture at GB20 improves cognitive ability and synaptic plasticity via the CaM–CaMKII–CREB signaling pathway following cerebral ischemia–reperfusion injury in rats

Han,

Wang

2023

Acupunct Med

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Background: This study aimed to investigate the effects of electroacupuncture (EA) on cognitive recovery and synaptic remodeling in a rat model of middle cerebral artery occlusion (MCAO) followed by reperfusion and explore the possible mechanism. Method: Focal cerebral ischemia was modeled in healthy adult Sprague-Dawley rats by MCAO. The MCAO rats were classified into four groups: sham, MCAO, MCAO + GB20 (receiving EA at GB20) and MCAO + NA (receiving EA at a “non-acupoint” location not corresponding to any traditional acupuncture point location about 10 mm above the iliac crest). Neurological deficit scores and behavior were assessed before and during the treatment. After intervention for 7 days, the hippocampus was dissected to analyze growth-associated protein (GAP)-43, synaptophysin (SYN) and postsynaptic density protein (PSD)-95 expression levels by Western blotting. Bioinformatic analysis and primary hippocampal neurons with calcium-voltage gated channel subunit alpha 1B (CACNA1B) gene overexpression were used to screen the target genes for EA against MCAO. Results: Significant amelioration of neurological deficits and learning/memory were found in MCAO + GB20 rats compared with MCAO or MCAO + NA rats. Protein levels of GAP-43, SYN and PSD-95 were significantly improved in MCAO + GB20–treated rats together with an increase in the number of synapses in the hippocampal CA1 region. CACNA1B appeared to be a target gene of EA in MCAO. There were increased mRNA levels of CACNA1B, calmodulin (CaM), Ca2+/calmodulin-dependent protein kinase type II (CaMKII) and cyclic adenosine monophosphate response element binding (CREB) and increased phosphorylation of CaM, CaMKII and CREB in the hippocampal region in MCAO + GB20 versus MCAO and MCAO + NA groups. CACNA1B overexpression modulated expression of the CaM–CaMKII–CREB axis. Conclusion: EA treatment at GB20 may ameliorate the negative effects of MCAO on cognitive function in rats by enhancing synaptic plasticity. EA treatment at GB20 may exert this neuroprotective effect by regulating the CACNA1B–CaM–CaMKII–CREB axis.

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Mouse Model of Middle Cerebral Artery Occlusion

Cited by 29 publications

References 4 publications

Observing Extracellular Vesicles Originating from Endothelial Cells in Vivo Demonstrates Improved Astrocyte Function Following Ischemic Stroke via Aggregation-Induced Emission Luminogens

Observing Extracellular Vesicles Originating from Endothelial Cells in Vivo Demonstrates Improved Astrocyte Function Following Ischemic Stroke via Aggregation-Induced Emission Luminogens

Mechanoresponsive Drug Delivery Systems for Vascular Diseases

Electroacupuncture at GB20 improves cognitive ability and synaptic plasticity via the CaM–CaMKII–CREB signaling pathway following cerebral ischemia–reperfusion injury in rats

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