scholarly journals Nanoliposomes Reduce Stroke Injury Following Middle Cerebral Artery Occlusion in Mice

2021 ◽  
Author(s):  
Saif Ahmad ◽  
Seth Truran ◽  
Nina Karamanova ◽  
Adam Kindelin ◽  
Maria Lozoya ◽  
...  
Keyword(s):  
Gene Expression ◽  
Middle Cerebral Artery ◽  
Middle Cerebral Artery Occlusion ◽  
Cerebral Artery ◽  
Quantitative Polymerase Chain Reaction ◽  
Neuroblastoma Cell ◽  
Artery Occlusion ◽  
Heme Oxygenase 1 ◽  
Neurologic Impairment ◽  
Cerebral Artery Occlusion

Neuroprotective strategies for stroke remain inadequate. Nanoliposomes comprised of phos-phatidylcholine, cholesterol and monosialogangliosides (NL) induced an antioxidant protective response in endothelial cells exposed to amyloid insults. We tested the hypotheses that NL will preserve SH-SY5Y neuroblastoma cell viability following hypoxic injury and will reduce injury in mice following middle cerebral artery occlusion (MCAO). Neuroblastoma were exposed to 20-hour physoxic (5% oxygen) or hypoxic (1% oxygen) condition without or with NL (100 or 300 µg/mL). Viability was measured using calcein-AM fluorescence and SH-SY5Y gene expression of antioxidant proteins heme oxygenase-1 (HO-1), NAD(P)H quinone dehydrogenase 1 (NQO1) and superoxide dismutase 1 (SOD1) were measured by quantitative polymerase chain reaction. C57BL/6J mice were treated with saline (N=8) or NL (10000 ug/mL, N=7) while undergoing 60-minute MCAO followed by reperfusion. Day 2 post-injury neurologic impairment score and infarction size were compared. Neuroblastoma showed reduced viability following hypoxia that was reversed by NL. NL increased gene expression of HO-1, NQO1 and SOD1 versus controls. NL-treated mice showed reduced neurologic impairment and brain infarct size (18.8±2% versus 27.3±2.3%, p=0.017) versus controls. NL reduced stroke injury in mice subjected to MCAO likely through induction of an antioxidant stress response. NL is a candidate novel agent for stroke.

scholarly journals RNA Sequencing for Gene Expression Profiles in a Rat Model of Middle Cerebral Artery Occlusion

2018 ◽  
Vol 2018 ◽  
pp. 1-14 ◽  
Author(s):  
Xianchun Duan ◽  
Jianghua Gan ◽  
Fan Xu ◽  
Lili Li ◽  
Lan Han ◽  
...  
Keyword(s):  
Gene Expression ◽  
Immune Response ◽  
Middle Cerebral Artery ◽  
Middle Cerebral Artery Occlusion ◽  
Rna Sequencing ◽  
Cerebral Artery ◽  
Expression Profiles ◽  
Artery Occlusion ◽  
Sequencing Analysis ◽  
Cerebral Artery Occlusion

Gene expression regulatory mechanisms in models of middle cerebral artery occlusion (MCAO) have been assessed in some studies, but questions remain. The discovery of differentially expressed genes (DEGs) between MCAO and control rats analyzed by next-generation RNA sequencing is of particular interest. These DEGs may help guide the clinical diagnosis of stroke and facilitate selection of the optimal treatment strategy. Twenty rats were equally divided into control and MCAO groups. Three rats from each group were randomly selected for RNA sequencing analysis. Sequence reads were obtained from an Illumina HiSeq2500 platform and mapped onto the rat reference genome RN6 using Hisat2. We identified 1,007 significantly DEGs with p<0.05, including 785 upregulated (fold change [FC]>2) and 222 downregulated (FC<0.5) DEGs, in brain tissue from MCAO rats compared with that from control rats, and numerous immune response genes were identified. Gene ontology (GO) analysis revealed that the majority of the most enriched and meaningful biological process terms were mainly involved in immune response, inflammatory response, cell activation, leukocyte migration, cell adhesion, response to external stimulus, cell migration, and response to wounding. Also enriched were immune-related pathways and neural-related pathways. Similar to GO molecular function terms, the enriched terms were mainly related to cytokine receptor activity. Six DEGs were verified by quantitative real-time polymerase chain reaction (qRT-PCR). Protein-protein interaction analysis of these hits revealed that MCAO affects complement and coagulation cascades and chemokine signaling pathway. Our study identified novel biomarkers that could help further elucidate MCAO mechanisms and processes.

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