Journal
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
Volume 22, Issue 9, Pages -Publisher
MDPI
DOI: 10.3390/ijms22095029
Keywords
carbonic anhydrase; inhibitors; sulfonamide; cerebral ischemia; middle cerebral artery occlusion; ischemic acidosis
Funding
- Italian Ministry for University and Research (MIUR) [PRIN 2017XYBP2R]
- University of Florence
- National Institute of Health
- Ente Cassa di Risparmio di Firenze [CRF18, CRF2020.1395]
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The review summarizes the role of carbonic anhydrase inhibitors in strokes and discusses their potential protective mechanisms, highlighting them as possible new pharmacological agents for the management of brain ischemia.
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.
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