Department of Neurosurgery, West Virginia University, Morgantown, West Virginia 26506-9183, USA.
Yale J Biol Med. 2012 Dec;85(4):523-39. Epub 2012 Dec 13.
Ischemic stroke represents a leading cause of morbidity and mortality in the developed world. This disabling and sometimes fatal event puts an ever increasing burden on the family members and medical professionals who care for stroke victims. Preclinical ischemic stroke research has predominantly utilized young adult, healthy animals, a clear discrepancy when considering the clinical population affected by stroke. A broad spectrum of risk factors such as age, obesity, diabetes, and hypertension has been associated with an increased stroke risk. The effect of these comorbidities on both stroke pathophysiology and outcome has not been emphasized and has been recognized as a shortcoming of preclinical studies. By addressing these conditions in experimental models of ischemic stroke, it may be possible to more accurately represent the clinical scenario and improve therapeutic translation from bench-to-bedside. In this work, we review many of the risk factors associated with increased stroke risk, particularly as each risk factor relates to inflammation. Additionally, we explore potential animal models that could be utilized in identifying the contribution of these risk factors to stroke outcome. By investigating the risk factors for stroke and how these may alter stroke pathophysiology, the present discrepancies between preclinical studies and the clinical reality can be reconciled in an effort to improve therapeutic development and translation from bench-to-bedside.
缺血性中风是发达国家发病率和死亡率的主要原因。这种致残甚至有时致命的事件给照顾中风患者的家庭成员和医疗专业人员带来了越来越大的负担。临床前缺血性中风研究主要使用年轻健康的成年动物，这与受中风影响的临床人群明显不符。年龄、肥胖、糖尿病和高血压等广泛的风险因素与中风风险增加有关。这些合并症对中风病理生理学和结果的影响尚未得到强调，被认为是临床前研究的一个缺点。通过在缺血性中风的实验模型中解决这些问题，可能更准确地代表临床情况，并提高从基础到临床的治疗转化。在这项工作中，我们回顾了许多与中风风险增加相关的风险因素，特别是每个风险因素与炎症的关系。此外，我们还探讨了可能用于确定这些风险因素对中风结果的影响的潜在动物模型。通过研究中风的风险因素以及这些因素如何改变中风的病理生理学，可以调和临床前研究和临床现实之间的差异，从而努力改善治疗的开发和从基础到临床的转化。
