Role of Carbonic Anhydrase in Cerebral Ischemia and Carbonic Anhydrase Inhibitors as Putative Protective Agents

Int J Mol Sci. 2021 May 10;22(9):5029. doi: 10.3390/ijms22095029.

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.

Keywords: carbonic anhydrase; cerebral ischemia; inhibitors; ischemic acidosis; middle cerebral artery occlusion; sulfonamide.

Publication types

  • Review

MeSH terms

  • Bicarbonates / metabolism
  • Brain / metabolism
  • Brain / pathology
  • Brain Ischemia / drug therapy*
  • Brain Ischemia / genetics
  • Brain Ischemia / pathology
  • Carbon Dioxide / metabolism
  • Carbonic Anhydrase Inhibitors / therapeutic use*
  • Carbonic Anhydrases / genetics*
  • Humans
  • Infarction, Middle Cerebral Artery / drug therapy
  • Infarction, Middle Cerebral Artery / genetics
  • Infarction, Middle Cerebral Artery / pathology
  • Ischemic Stroke / drug therapy*
  • Ischemic Stroke / genetics
  • Sulfonamides / therapeutic use

Substances

  • Bicarbonates
  • Carbonic Anhydrase Inhibitors
  • Sulfonamides
  • Carbon Dioxide
  • Carbonic Anhydrases