Searching evidences of stroke in animal models: a review of discrepancies

Abstract

ABSTRACTcan be replaced with ketone bodies. In total starvation such as global cerebral ischemia, the brain's limited reserves of glycogen and glucose are barely able to fuel normal brain activity up to 5 minutes. It is reported that the energy stores of the brain are equivalent to 20 cl/100 gr (39). In a healthy person, cerebral blood flow (CBF) is autoregulated at 45-50 ml/100gr/min with a mean arterial blood pressure (MABP) of 60-130 mm/Hg (Figure 1). In the cerebral ischemia model, the investigators try to reduce the oxygen and glucose supply of cerebral tissue. This process produces ischemic brain injury via a variety of cellular and molecular mechanisms.There are three major types of ischemic stroke models: global, focal and lacunar. The global ischemic model is produced by occlusion of four (both vertebral and carotid arteries) or two vessels (either both carotid or vertebral arteries) with or without concomittant hypotension during ischemia period (38). In this model, global blood flow is ceased completely, which resembles the condition of cardiac arrest or coronary █ LITERATuRE REvIEw METhODS O ur review method was based on articles dealing with the relations between animal models and clinical trials. By performing a PubMed search, we aimed to identify all relevant papers to call attention to the discrepancy between experimental methodology in animal modeling and clinical experiences. Articles that were referenced by reviewed articles were also evaluated. Data from papers were extracted within the following categories: study design, type of study population, sampling strategy. Articles excluded from the review were studies that were describing surgical techniques, experimental design and methodology. █ An OvERvIEw Of STROkE MODELSThe human adult brain consumes about 8 cal/100 gr/min energy. Normally, almost 100% of glucose is metabolised, but if starved this increases up to 30%, and glucose consumption So far, animal models have helped us better understand the pathophysiology of the ischemic brain damage but they could not contribute so much to clinical practice. The discrepancies in results regarding neuroprotective agents in animal experiments compared to clinical trials have not been solved. Various animal models of ischemic stroke have proven efficacy of many neuroprotective agents without any considerable result in phase III clinical trials.As is well known, stroke-related focal cerebral ischemia or cardiac arrest related global cerebral ischemia are major causes of disability and death among human subjects. Animal models are essential to evaluate the therapeutic approaches for humans.In this review, we will try to answer two important questions: 1) Which factors endanger the reliability of experimental studies of stroke on animal models? 2) How can we design our experiments to reflect the neurorestoration and/or neuroprotection mechanisms following ischemic injury, when it comes to human disease?

P53 expression in ischemic rat models after the administration of ketamine and ketamine-xylazine

“…One of the models for global ischemic brains is transient bilateral common carotid artery occlusion (tBCCAO). The tBCCAO has a higher significance than other ischemic models, mainly because its induced mortality rate is lower than that of focal ischemic brain models (MCAO) (Kaya et al, 2016). Also, it can be used to explain some ischemic condition in humans, such as ischemia caused by a heart attack, diabetes, or vascular dementia (Sanderson and Wider, 2013;Barbhuiya et al, 2015;Traystman, 2003;Kim et al, 2008;van der Spuy et al, 2015;Wang et al, 2016).…”

Transient Bilateral Common Carotid Artery Occlusion (tBCCAO) of Rats as a Model of Global Cerebral Ischemia

“…A good experimental animal model is important to support the success of research on disease pathogenesis and drug development, including research in the field of neurological diseases. However, several systematic reviews suggest that the successful use of drugs for nervous system protection in the experimental model was not confirmed by the stage III of clinical trials [1][2][3] . Of 700 types of drugs used in the brain ischemia model, only recombinant tissue plasminogen activator (rt-PA) and aspirin have efficacy 4,5 .…”

Adaptive Role of Glial Cell Line-Derived Neurotrophic Factor in Cerebral Ischemia

“…Currently, most in vivo studies are carried out on such models as middle cerebral artery occlusion or a threadocclusion method by nylon strand introduction into the middle cerebral artery [5][6][7]. These models are able to create a focal ischemic injury.…”