AI Article Synopsis
- * Carbonic anhydrase (CA) plays an important role in regulating pH levels, and new inhibitors like AN11-740 and AN6-277, along with acetazolamide (ACTZ), were tested for their protective effects in two brain ischaemia models in rats.
- * The study found that these CA inhibitors delayed harmful effects in brain tissue and improved outcomes by reducing neurological deficits, infarct volume, and neuronal loss, while also lowering microglia activation and astrocyte degeneration.
Article Abstract
Ischaemic stroke is a leading cause of death and disability. One of the major pathogenic mechanisms after ischaemia includes the switch to the glycolytic pathway, leading to tissue acidification. Carbonic anhydrase (CA) contributes to pH regulation. A new generation of CA inhibitors, AN11-740 and AN6-277 and the reference compound acetazolamide (ACTZ) were investigated in two models of brain ischaemia: in rat hippocampal acute slices exposed to severe oxygen, glucose deprivation (OGD) and in an model of focal cerebral ischaemia induced by permanent occlusion of the middle cerebral artery (pMCAo) in the rat. , the application of selective CAIs significantly delayed the appearance of anoxic depolarisation induced by OGD. , sub-chronic systemic treatment with AN11-740 and ACTZ significantly reduced the neurological deficit and decreased the infarct volume after pMCAo. CAIs counteracted neuronal loss, reduced microglia activation and partially counteracted astrocytes degeneration inducing protection from functional and tissue damage.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8168743 | PMC |
| http://dx.doi.org/10.1080/14756366.2021.1907575 | DOI Listing |
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