Ischemic stroke is the fifth leading cause of death in the USA and is the leading cause of serious, long-term disability worldwide. The principle sex hormones (estrogen, progesterone, and testosterone), both endogenous and exogenous, have profound effects on various stroke outcomes and have become the focus of a number of studies evaluating risk factors and treatment options for ischemic stroke. In addition, the expression of other hormones that may influence stroke outcome, including select adipose-derived hormones (adiponectin, leptin, and ghrelin), can be regulated by sex hormones and are also the focus of several ischemic stroke studies. This review aims to summarize some of the preclinical and clinical studies investigating the principle sex hormones, as well as select adipose-derived hormones, as risk factors or potential treatments for ischemic stroke. In addition, the potential for relaxin, a lesser studied sex hormone, as a novel treatment option for ischemic stroke is explored.
Stroke is the fifth leading cause of death in the United States, and is the leading cause of serious, long-term disability worldwide. There are at least 795,000 new or recurrent strokes each year, and approximately 85% of all stroke occurrences are ischemic. Unfortunately, companion animals are also at risk for ischemic stroke. Although the exact incidence of ischemic stroke in companion animals is unknown, some studies, and the veterinary information network (VIN), report that approximately 3% of neurological case referrals are due to a stroke. There is a long list of predisposing factors associated with the risk of ischemic stroke in both humans and canines; however, these factors do not explain why a stroke happens at a particular time on a particular day. Our understanding of these potential stroke "triggers" is limited, and the effect of transient environmental exposures may be one such "trigger". The present study investigated the extent to which the natural occurrence of canine ischemic stroke was related to the weather conditions in the time-period immediately preceding the onset of stroke. The results of the present study demonstrated that the change in weather conditions could be a potential stroke trigger, with the strokes evaluated occurring after periods of rapid, large fluctuations in weather conditions. There are currently no epidemiological data on the seasonal variability of ischemic stroke in dogs, and determining whether canine stroke parallels human stroke would further validate the use of companion dogs as an appropriate naturally occurring model.
Rodent and rabbit stroke models have been instrumental in our current understanding of stroke pathophysiology; however, translational failure is a significant problem in preclinical ischemic stroke research today. There are a number of different focal cerebral ischemia models that vary in their utility, pathophysiology of causing disease, and their response to treatments. Unfortunately, despite active preclinical research using these models, treatment options for ischemic stroke have not significantly advanced since the food and drug administration approval of tissue plasminogen activator in 1996. This review aims to summarize current stroke therapies, the preclinical experimental models used to help develop stroke therapies, as well as their advantages and limitations. In addition, this review discusses the potential for naturally occurring canine ischemic stroke models to compliment current preclinical models and to help bridge the translational gap between small mammal models and human clinical trials.
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