Stroke and Translational Research - Review of Experimental Models with a Focus on Awake Ischaemic Induction and Anaesthesia.

ABSTRACT

Animal models are an indispensable tool in the study of ischaemic stroke with hundreds of drugs emerging from the preclinical pipeline. However, all of these drugs have failed to translate into successful treatments in the clinic. This has brought into focus the need to enhance preclinical studies to improve translation. The confounding effects of anaesthesia on preclinical stroke modelling has been raised as an important consideration. Various volatile and injectable anaesthetics are used in preclinical models during stroke induction and for outcome measurements such as imaging or electrophysiology. However, anaesthetics modulate several pathways essential in the pathophysiology of stroke in a dose and drug dependent manner. Most notably, anaesthesia has significant modulatory effects on cerebral blood flow, metabolism, spreading depolarizations, and neurovascular coupling. To minimise anaesthetic complications and improve translational relevance, awake stroke induction has been attempted in limited models. This review outlines anaesthetic strategies employed in preclinical ischaemic rodent models and their reported cerebral effects. Stroke related complications are also addressed with a focus on infarct volume, neurological deficits, and thrombolysis efficacy. We also summarise routinely used focal ischaemic stroke rodent models and discuss the attempts to induce some of these models in awake rodents.