Diabetes mitigates the recovery following intracranial hemorrhage in rats

Behav Brain Res. 2017 Mar 1:320:412-419. doi: 10.1016/j.bbr.2016.10.047. Epub 2016 Nov 3.

Abstract

Intracranial hemorrhage (ICH) is a common subtype of stroke with high morbidity and mortality. However, few studies have examined the effects of diabetes on the recovery from ICH-induced brain injury. Therefore, we examined the effects of diabetes on protein levels of aquaporins, neuronal loss, angiogenesis, blood brain barrier (BBB) integrity, and neurological deficits following intra-DH collagenase-induced ICH in the hippocampus. We found that diabetic rats exhibited enhanced AQP9 expression in the hippocampus relative to non-diabetic rats, which was associated with increased behavioral deficits. Additionally, ICH induced neovascularization, proliferation of brain microvascular endothelial cells, and hippocampal neuronal loss. However, ICH-induced neovascularization and proliferation of brain microvascular endothelial cells was severely impaired in diabetic rats. Furthermore, ICH-induced hippocampal neuronal loss was exaggerated in diabetic rats. Finally, ICH impaired BBB integrity in the ipsilateral hemisphere, which was increased in diabetic rats. Taken together, the attenuated brain angiogenesis, increased hippocampal neuronal loss, and impaired BBB integrity in diabetic rats after ICH were associated with enhanced AQP9 expression. This may suggest that AQP9 is one of the underlying mechanisms that can mitigate the recovery from ICH in diabetic populations.

Keywords: Angiogenesis; Aquaporin 9; Hippocampus; Intracranial hemorrhage; Neuronal loss.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Aquaporins / metabolism
  • Blood-Brain Barrier / pathology
  • Collagenases / toxicity
  • Diabetes Mellitus, Experimental / pathology
  • Diabetes Mellitus, Experimental / physiopathology*
  • Disease Models, Animal
  • Gene Expression Regulation / drug effects
  • Gene Expression Regulation / physiology*
  • Hippocampus / metabolism*
  • In Situ Nick-End Labeling
  • Intracranial Hemorrhages / chemically induced
  • Intracranial Hemorrhages / pathology
  • Intracranial Hemorrhages / physiopathology*
  • Male
  • Occludin / genetics
  • Occludin / metabolism
  • Proliferating Cell Nuclear Antigen / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Recovery of Function / drug effects
  • Recovery of Function / physiology*
  • Zonula Occludens-1 Protein / genetics
  • Zonula Occludens-1 Protein / metabolism
  • von Willebrand Factor / metabolism

Substances

  • Aqp9 protein, rat
  • Aquaporins
  • Occludin
  • Proliferating Cell Nuclear Antigen
  • Tjp1 protein, rat
  • Zonula Occludens-1 Protein
  • von Willebrand Factor
  • Collagenases