Department of Neuroscience, Psycology, Drug Research and Child Health (NEUROFARBA), Section of Pharmacology and Toxicology, University of Florence, 50139 Florence, Italy.
Department of Neuroscience, Psycology, Drug Research and Child Health (NEUROFARBA), Section of Pharmaceutical Sciences, University of Florence, 50019 Florence, Italy.
Int J Mol Sci. 2021 May 10;22(9):5029. doi: 10.3390/ijms22095029.
Ischemic stroke is a leading cause of death and disability worldwide. The only pharmacological treatment available to date for cerebral ischemia is tissue plasminogen activator (t-PA) and the search for successful therapeutic strategies still remains a major challenge. The loss of cerebral blood flow leads to reduced oxygen and glucose supply and a subsequent switch to the glycolytic pathway, which leads to tissue acidification. Carbonic anhydrase (CA, EC 4.2.1.1) is the enzyme responsible for converting carbon dioxide into a protons and bicarbonate, thus contributing to pH regulation and metabolism, with many CA isoforms present in the brain. Recently, numerous studies have shed light on several classes of carbonic anhydrase inhibitor (CAI) as possible new pharmacological agents for the management of brain ischemia. In the present review we summarized pharmacological, preclinical and clinical findings regarding the role of CAIs in strokes and we discuss their potential protective mechanisms.
缺血性脑卒中是全球范围内主要的致死和致残病因。迄今为止，可用于治疗脑缺血的唯一药物是组织型纤溶酶原激活物（t-PA），因此寻找有效的治疗策略仍然是一个主要挑战。脑血流的减少会导致氧和葡萄糖供应减少，随后转向糖酵解途径，导致组织酸化。碳酸酐酶（CA，EC 4.2.1.1）是将二氧化碳转化为质子和碳酸氢根的酶，有助于调节 pH 值和代谢，大脑中存在多种 CA 同工酶。最近，许多研究揭示了几类碳酸酐酶抑制剂（CAI）作为治疗脑缺血的可能新的药理学药物。在本综述中，我们总结了 CAI 在中风中的药理学、临床前和临床研究结果，并讨论了它们的潜在保护机制。
