Acetazolamide alleviates sequelae of hyperglycaemic intracerebral haemorrhage by suppressing astrocytic reactive oxygen species

Abstract

Hyperglycaemia is associated with the poor outcome after intracerebral haemorrhage (ICH). Acetazolamide (AZA), a kind of carbonic anhydrogenase (CA) inhibitor, its effectiveness in ICH had been reported. However, the connections between AZA and ICH, especially in hyperglycaemia condition had never been defined. In this study, adult Sprague-Dawley rats were administered with vehicle or streptozotocin (STZ) to render them into normoglycaemic (NG) or hyperglycaemic (HG), respectively. Collagenase was then injected into the striatum. The NG or HG ICH rats treated with vehicle control or 5 mg/kg AZA (oral gavage) underwent haemorrhagic area assessments on the 1st, 4th, and 7th day after ICH. The coverage of pericytes was examined by immunohistochemistry. Reactive oxygen species (ROS) levels were assessed in mouse astrocyte cell line treated with vehicle or 20 μmol/L of AZA in culture media according to two different glucose concentrations. AZA reduced the haematoma size, improved neurobehavioral functions, suppressed astrocytic ROS production in vitro, and preserved cerebral pericytes coverage, which are even more remarkable in HG conditions. The present study indicates that AZA may alleviate some sequelae after ICH, especially in poorer prognostic HG rats through the suppression of astrocytic ROS production.

A Multi-Model Pipeline for Translational Intracerebral Haemorrhage Research

“…The main models discussed in this section represent major risk factors for ICH in patients: hypertension, cerebral amyloid angiopathy (CAA) and cerebral small vessel disease (CSVD). The HEADS committee also highlighted the need to develop models of modifiable and non-modifiable risk factors, such as alcoholism and ageing to further understand how ICH can be prevented in these populations, as there are relatively few papers which utilise these risk factors [20,[56][57][58][59][60][61][62][63].…”

An Update On Medical Treatment for Intracerebral Hemorrhage

“…These free radicals' accumulation in brain tissues could damage neurons and endothelial cells, and induce microglia activation. Therefore, the scavengers of free radicals, such as melatonin, edaravone, isoliquiritigenin, acetazolamide, and so on, show improvement effects on ICHinduced SBI by inhibiting oxidative stress in the preclinical researches [29][30][31][32][33]. However, the clinical trial is not satisfactory.…”