Development of a Modified Surgical Technique for Simulating Ischemic Cerebral Cortex Injury in Rats

Yeh, Ching-Fa; Chuang, Tung-Yueh; Hung, Yu-Min; Lan, Ming‐Ying; Tsai, Ching-Han; Huang, Hao-Xiang; Lin, Yung-Yang

doi:10.21873/invivo.11588

Cited by 7 publications

(6 citation statements)

References 13 publications

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“…Focal cerebral ischemia with MCAO was achieved by the procedures which we previously described 40. Briefly, rats were anesthetized with Zoletil (30 mg/kg) and Xylazine (8 mg/kg) by intraperitoneal (i.p.)…”

Section: Methodsmentioning

confidence: 99%

<p>Soluble epoxide hydrolase inhibition enhances anti-inflammatory and antioxidative processes, modulates microglia polarization, and promotes recovery after ischemic stroke</p>

Yeh¹,

Chuang²,

Hung³

et al. 2019

NDT

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BackgroundIschemic stroke triggers inflammatory responses and oxidative stress in the brain, and microglia polarization affects the degree of neuroinflammation. It has been reported that the inhibition of soluble epoxide hydrolase (sEH) activity protects brain tissue. However, the anti-inflammatory and antioxidative effects of sEH inhibition in the ischemic brain are not fully understood. This study aimed to investigate the effects of a selective sEH inhibitor, 12-(3-adamantan-1-yl-ureido)-dodecanoic acid (AUDA), after ischemic stroke.MethodsAdult male rats with middle cerebral artery occlusion (MCAO) were administered with AUDA or a vehicle. Behavioral outcome, infarct volume, microglia polarization, and gene expression were assessed.ResultsRats treated with AUDA showed better behavioral outcomes and smaller infarct volumes after MCAO. After AUDA treatment, a reduction of M1 microglia and an increase of M2 microglia occurred at the ischemic cortex of rats. Additionally, there was an increase in the mRNA expressions of antioxidant enzymes and anti-inflammatory interleukin-10, and pro-inflammatory mediators were decreased after AUDA administration. Heme oxygenase-1 was mainly expressed by neurons, and AUDA was found to improve the survival of neurons.ConclusionThe results of this study provided novel and significant insights into how AUDA can improve outcomes and modulate inflammation and oxidative stress after ischemic stroke.

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Section: Methodsmentioning

confidence: 99%

<p>Soluble epoxide hydrolase inhibition enhances anti-inflammatory and antioxidative processes, modulates microglia polarization, and promotes recovery after ischemic stroke</p>

Yeh¹,

Chuang²,

Hung³

et al. 2019

NDT

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“…However, this method has a significant limitation, such as a high mortality rate of 71-100% in diver strains of rats (Schulte-Herbrüggen et al, 2006). Another alternative method is using craniotomy (Yeh et al, 2019). A craniotomy is an invasive method that can be applied in rat models.…”

Section: Resultsmentioning

confidence: 99%

Standardization of the Simple Methodology for Experimentally Induced Ischemic Stroke in Rat Models

Prakoso,

Sigit,

Aliviameita

2023

WVJ

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Stroke is a globally significant and devastating disease that requires prompt treatment. Animal models are commonly used to investigate stroke therapy, often through experimentally induced ischemic stroke (EIIS). However, challenges arise in implementing EIIS in animal models. The current study aimed to present a simple EIIS methodology for animal models. A total of 60 male Sprague-Dawley rats were randomly divided into five groups, namely Group 1 (sham-operated), Groups 2 to 5 (EIIS groups) with different duration of common carotid artery (CCA) ligation, including 1, 2, 4, and 8 hours, respectively. The ligation was performed on the CCA and its branches. Before the experiment, the rats were anesthetized, and the incision area was shaved and disinfected. The sagittal ventral midline was incised, with neck muscles retracted to expose the right CCA. The occlusion was performed on three sides of a carotid artery (common, external, and internal) using a simple interrupted suture. The occlusion of blood flow using ligation was performed at different times depending on the groups. After that, the CCA ligations were re-perfused by cutting the suture knot. The brain and blood were collected on days 1 and 7 after reperfusion. The results indicated that 4 and 8 hours of CCA ligation significantly impacted the general condition and neuro-deficit score. Moreover, 4 and 8 hours of CCA ligation could induce ischemic stroke by its capacity to cause infarction within the brain parenchyma and increase the platelet-to-white blood cell ratio, C-reactive protein, and De Ritis ratio. In contrast, 1 and 2 hours of CCA ligation did not significantly affect the observed parameters. It can be concluded that the EIIS using 4 and 8 hours of CCA ligation can be applied to induce ischemic stroke in rat models with consistent impacts on general conditions, neuro-deficit, hematology, and serology.

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“…Moreover, this surgical method reduces the mortality rate of experimental animals, which greatly reduces the number of experimental animals used. This animal model is widely used for stroke research (17,18).…”

Section: Discussionmentioning

confidence: 99%

Bifico Ameliorates Neurological Deficits After Ischemic Stroke in Mice: Transcriptome Profiling

HAN,

XU,

TAO

et al. 2024

In Vivo

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Background/Aim: Evidence suggests that gut microbiota can affect various neurological diseases, including stroke. Stroke patients have an increase in harmful gut bacteria and a decrease in beneficial bacteria. This increases intestinal permeability, increases the risk of infection, and even affects many inflammatory factors. While probiotics may affect stroke prognosis by improving the gut environment. This study aimed to investigate the effect of probiotic Bifico on the neural function in mice after focal cerebral ischemia and explore its mechanisms of action. Materials and Methods: A focal cerebral ischemia model was established in mice. Four weeks before modeling, animals were divided into three groups: Stroke plus Vehicle group, Stroke plus Pre-Bifico group and Bifico group. The infarct volume and neurobehaviors were evaluated. Wholegene expression profiling was performed at different days after treatment (D1, D7, D14, D28) by RNA-seq. Differentially expressed genes (DEGs) were the processed for Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG). Some inflammation and immune related genes were screened and their expression was analyzed. Results: Compared to the Stroke plus Vehicle group and Bifico group, the infarct volume and neurological score were significantly reduced in the Pre-Bifico group. There were 2 DEGs at D1, 193 DEGs at D7, 70 DEGs at D28 between Stroke plus Pre-Bifico group and Stroke plus Vehicle group. For GO analysis, there were 139 significant terms at D7 and 195 at D28. For KEGG, there were 2 significant pathways at D7 and 9 at D28. Among 87 genes related to inflammation and immunity, 6 DEGs were identified. The expression of CCL9 was significantly elevated at most time points after stroke compared to the Stroke plus Vehicle group, while that of CCL6, CXCL10, CD48, CD72 and CLEC7A was highly expressed only in the recovery stage of stroke. Conclusion: Oral pre-treatment with Bifico for 28 days can reduce cerebral infarction and promote recovery of neurological function in stroke mice, which may be ascribed to the regulation of immunity and inflammation in the brain.Ischemic stroke is a major cause of disability and death and has been a critical public health problem which causes a heavy social and economic burden worldwide. This is expected to get worse as population is aging. However, due to the short thrombolytic time window and concerns of safety and medical cost, only a very small number of patients receive thrombolysis and endovascular treatment. Therefore, to explore the mechanisms of ischemic brain injury and repair and to identify potential therapeutic targets for stroke have been hot topics in neuroscience researches.Recently, studies have shown that the intestinal microbiota plays a significant role in the interaction between brain and distant organs such as the intestine, which is commonly referred to as the intestinal brain axis or the microbiota intestinal brain (MGB) axis (1). MGB axis acts as a communication portal integrating nerve, horm...

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Development of a Modified Surgical Technique for Simulating Ischemic Cerebral Cortex Injury in Rats

Cited by 7 publications

References 13 publications

<p>Soluble epoxide hydrolase inhibition enhances anti-inflammatory and antioxidative processes, modulates microglia polarization, and promotes recovery after ischemic stroke</p>

<p>Soluble epoxide hydrolase inhibition enhances anti-inflammatory and antioxidative processes, modulates microglia polarization, and promotes recovery after ischemic stroke</p>

Standardization of the Simple Methodology for Experimentally Induced Ischemic Stroke in Rat Models

Bifico Ameliorates Neurological Deficits After Ischemic Stroke in Mice: Transcriptome Profiling

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