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

Free Radic Res. 2018 Sep;52(9):1010-1019. doi: 10.1080/10715762.2018.1508838. Epub 2018 Sep 21.

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.

Keywords: Acetazolamide; astrocytes; hyperglycaemia; intracerebral haemorrhage; reactive oxygen species.

MeSH terms

  • Acetazolamide / administration & dosage*
  • Animals
  • Astrocytes / drug effects
  • Astrocytes / pathology
  • Cerebral Hemorrhage / complications
  • Cerebral Hemorrhage / drug therapy*
  • Cerebral Hemorrhage / physiopathology
  • Collagenases / administration & dosage
  • Corpus Striatum / drug effects
  • Corpus Striatum / pathology
  • Diabetes Mellitus, Experimental / chemically induced
  • Diabetes Mellitus, Experimental / drug therapy*
  • Diabetes Mellitus, Experimental / pathology
  • Glucose / metabolism
  • Humans
  • Hyperglycemia / complications
  • Hyperglycemia / drug therapy*
  • Hyperglycemia / physiopathology
  • Mice
  • Rats
  • Reactive Oxygen Species / metabolism

Substances

  • Reactive Oxygen Species
  • Collagenases
  • Glucose
  • Acetazolamide