Anesthesia in Experimental Stroke Research

Abstract

Anesthetics have enabled major advances in development of experimental models of human stroke. Yet their profound pharmacologic effects on neural function can confound the interpretation of experimental stroke research. Anesthetics have drug and dose-specific effects on cerebral blood flow and metabolism, neurovascular coupling, autoregulation, ischemic depolarizations, excitotoxicity, inflammation, neural networks, and numerous molecular pathways relevant for stroke outcome. Both pre- and post-conditioning properties have been described. Anesthetics also modulate systemic arterial blood pressure, lung ventilation, and thermoregulation, all of which may interact with the ischemic insult as well as the therapeutic interventions. These confounds present a dilemma. Here, we provide an overview of the anesthetic mechanisms of action and molecular and physiologic effects on factors relevant to stroke outcomes that can guide the choice and optimization of the anesthetic regimen in experimental stroke.

Alpha-7 Nicotinic Receptor Signaling Pathway Participates in the Neurogenesis Induced by ChAT-Positive Neurons in the Subventricular Zone

“…Briefly, we anesthetized mice with an intraperitoneal (i.p.) injection of 4% chloral hydrate (0.007 mL/g) and made a midline incision in the ventral side of the neck to expose the carotid arteries[23]. We carefully separated the arteries from their sheaths and adjacent vagus nerves.…”

To Improve Translational Research in Subarachnoid Hemorrhage

“…The proposed standards include (1) clinical relevance of animal models (detailed information on animals used (species, strain, age, weight, gender, etc. ), selection of anesthetics, inclusion and exclusion criteria), (2) sample size calculation and accurate statistical analysis, (3) treatment (randomization, allocation concealment, dose-response determinations, therapeutic time window, blood-brain barrier permeability and tissue drug levels, physiological monitoring), (4) outcome (blinded assessment, at least two outcome measures (morphology and function), covering both acute (1-3 days) and longterm (7-30 days) endpoints), and (5) reporting of animals excluded from analysis, potential conflicts of interest, and study funding [1][2][3][4][5][6][7]. In addition, several challenges exist to successfully translate the outcomes from animal research to humans in a clinical setting.…”

“…However, the male-biased use of research animals is distinguished from the clinical situation where there is a disproportionate and growing female stroke population, making it important to include both sexes with diverse ages in preclinical as well as clinical studies that evaluate potential stroke therapies. Second, cerebrovascular anatomy and collaterals, as well as biological and secondary neuroinflammatory responses to insults, are different between species or strains, causing flawed design, unreliable outcomes, unnecessarily more costs, and experimental animals [7,[9][10][11]. Genetic differences between animals and humans, and even within animal species, strains, and cell lines, may affect the immune responses and outcomes [10,12,13].…”

Can Quality Improvement Tools Overcome the Translational Roadblock—the Vital Influence of the Researcher

“…Novel approaches have been proposed to minimize bias and improve translational success. These strategies range from engaging multiple laboratories in preclinical trials [1], to increasing awareness of the importance of sex, age, and strain-related differences [2,3], recognizing biological and methodological variances [4], the impact of diseasespecific comorbidities [5] and anesthetics [6] on measured endpoints, and using proper outcome modalities [7][8][9] in experimental stroke research.…”