Chick Embryo: A Preclinical Model for Understanding Ischemia-Reperfusion Mechanism.

Syed Shadab Raza,Manish Kumar,Paarth Garg,Eram Fauzia,Avril A B Robertson,Tarun Kumar Barbhuyan,Amit Kumar Shrivastava,Mohsin Ali Khan

doi:10.3389/fphar.2018.01034

Abstract

Ischemia-reperfusion (I/R)-related disorders, such as stroke, myocardial infarction, and peripheral vascular disease, are among the most frequent causes of disease and death. Tissue injury or death may result from the initial ischemic insult, primarily determined by the magnitude and duration of the interruption in blood supply and then by the subsequent reperfusion-induced damage. Various in vitro and in vivo models are currently available to study I/R mechanism in the brain and other tissues. However, thus far, no in ovo I/R model has been reported for understanding the I/R mechanisms and for faster drug screening. Here, we developed an in ovo Hook model of I/R by occluding and releasing the right vitelline artery of a chick embryo at 72 h of development. To validate the model and elucidate various underlying survival and death mechanisms, we employed imaging (Doppler blood flow imaging), biochemical, and blotting techniques and evaluated the cell death mechanism: autophagy and inflammation caused by I/R. In conclusion, the present model is useful in parallel with established in vitro and in vivo I/R models to understand the mechanisms of I/R development and its treatment.

Highlights

The incidence of ischemia-reperfusion (I/R) injury is high, and its pathogenesis involves complex, multifactorial, and interrelated processes
Functional changes in vascularization during the I/R period were mapped through laser Doppler perfusion imaging, which is widely used for microcirculatory imaging in human and rodents; to the best of our knowledge, this is the first instance in which this technique has been used to monitor blood flow in a chick model
To verify that the Hook I/R model can be used for drug screening, we evaluated the protective effect of meldonium dihydrate (MD), trimetazidine (TMZ), MCC950, and N-acetyl cysteine (NAC)

Summary

Introduction

The incidence of ischemia-reperfusion (I/R) injury is high, and its pathogenesis involves complex, multifactorial, and interrelated processes. To mimic the aforementioned mechanism, suitable models closely resembling human pathology in clinical conditions are needed, that can contribute to our understanding of the mechanisms underlying I/R injury (Milcan et al, 2004; Lai et al, 2006; Kalogeris et al, 2012, 2016; Horvath et al, 2016; Ross et al, 2016; McBride and Zhang, 2017). Such models aid the understanding of I/R mechanisms and are used in drug testing pipelines; translating to improved patient care

Objectives

Results

Conclusion