Abstract
Stroke is a cerebrovascular pathology for which the only approved treatment is fibrinolysis. Several studies have focused on the development of new drugs but none has led to effective therapies to date, due, among others, to the difficulty to evaluate clinical deficits in experimental animal models. The present study aims to explore the applicability of known behavioral tests not commonly used in ischemia for the neurological assessment of mice after experimental stroke in different brain areas. A total of 225 CD1 male mice were randomly assigned to permanent middle cerebral artery occlusion by ligature (pMCAO) or permanent anterior cerebral artery occlusion by photothrombosis (pACAO) models. Modified neuroseverity score, footprint test, forced swim test and elevated plus maze were performed. Under these experimental conditions, modified neuroseverity score showed neurological impairment early after experimental stroke in both models. By contrast, the footprint test and the elevated plus maze detected short-term neurological deterioration in the pMCAO model but not in the pACAO model. Furthermore, the forced swim test identified depression-like behavior in mice after ischemia only when the left hemisphere was affected. In conclusion, we propose the repositioning of known neurobehavioral tests, but not commonly used in the stroke field, for the fast detection of neurological impairments early after ischemia, and even specific to discriminate the territory affected by arterial occlusion as well as the hemisphere where brain damage occurs. All these findings may prove useful to improve the experimental design of neuroprotective drugs in order to bridge the gap between experimental studies and clinical trials.
Highlights
Stroke is one of the main causes of death and disability in developed countries, and it has been classed as a medical emergency
Since there is a need of novel and sensitive outcome measures with translational applicability, the present study aims to explore the usefulness of known behavioural tests, not commonly used in ischemia, for the neurological assessment of mice after experimental stroke in different brain areas
Exposure to 8-week-old CD1 mice to permanent MCAO or permanent ACAO induced similar infarct volumes expressed in percentage of infarct hemisphere
Summary
Stroke is one of the main causes of death and disability in developed countries, and it has been classed as a medical emergency. Several initiatives have been proposed to overcome the lack of translation of preclinical studies to human clinical trials. It has been proposed the need to assess the functional response in addition to infarct volume as outcome measures that may help to bridge the gap from animal research to human trials [1]. Identifying behavioral deficits in animal stroke models is essential for potential translational applications. In this context, in contrast to the availability of tests for clinical evaluation of patients after stroke, mouse neurobehaviour after cerebral ischemia remains difficult to assess due to the fact that most available tests are adapted from rats [2, 3, 4]. As a consequence of all these factors, several authors have shown opposite results in the evaluation of deficits after experimental ischemia based on the species, strain, age and experimental model used as well as on the time at which the test is performed [6, 7, 8]
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