Abstract
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.
Highlights
Accepted: 7 May 2021Ischemic stroke is the second most common cause of death and a major cause of long-term disability worldwide and it is considered a global burden
Since multiple carbonic anhydrases (CAs) isoforms are expressed in cerebral arteries, carbonic anhydrase inhibitor (CAI), by decreasing intracellular acidosis, may protect the ischemia-induced blood-brain barrier (BBB) breakdown in the cerebrovascular wall during middle cerebral artery occlusion (MCAo)
Protection in vivo by CAIs against brain hypoxic/ischemic damage may be due to reduction of tissue acidosis and early glutamate excitotoxicity, protection by CAIs may be related to different effects
Summary
Ischemic stroke is the second most common cause of death and a major cause of long-term disability worldwide and it is considered a global burden. It is characterized by early glutamate-mediated excitotoxicity, followed by a chronic secondary damage caused by the activation of resident immune cells, i.e., microglia, and the production of inflammatory mediators [1]. The occlusion leads to a reduction of cerebral blood flow rate, a condition of hypoxia and Published: 10 May 2021. The occlusion leads to a reduction of cerebral blood flow rate, a condition of hypoxia and glucose deprivation (oxygen, glucose deprivation: OGD).
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