Enhanced Connexin 43 Immunoreactivity in Penumbral Areas in the Human Brain Following Ischemia

Glia. 2006 Oct;54(5):369-75. doi: 10.1002/glia.20399.

Abstract

Astrocytes support neurons not only physically but also chemically by secreting neurotrophic factors and energy substrates. Moreover, astrocytes establish a glial network and communicate through gap junctions in the brain. Connexin 43 (Cx43) is one of major component proteins in astrocytic gap junctions. Heterozygote Cx43 KO mice and astrocyte specific Cx43 KO mice exhibited amplified brain damage after ischemic insults, suggesting a neuroprotective role for astrocytic gap junctions. However, some reports mentioned unfavorable effects of gap junctions in neuronal support. Therefore, the role of astrocytic gap junctions under ischemic condition remains controversial. Since these studies have been performed using animal models, we investigated the Cx43 expression in human brain after stroke. Brain slice sections were prepared from pathological samples in our hospital. Embolic stroke brains sectioned because of the stroke were considered as acute ischemic models. Multiple infarction brains sectioned because of pneumonia or cancer were considered as chronic models. We observed the levels of Cx43 in both lesioned and intact areas, and compared them with acute and chronic models. As the results, astrocytes were strongly activated in penumbral lesions both of acute and chronic ischemic models. The Cx43 immunoreactivity was significantly amplified in the penumbra of chronic model compared to that of the acute model. Neurons were well preserved in chronic model compared to acute model. These findings suggested that the brain may generate neuronal protection by increasing the levels of Cx43 and amplifying the astrocytic gap junctional intercellular communication under hypoxic condition.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Disease
  • Aged
  • Aged, 80 and over
  • Astrocytes / metabolism*
  • Brain / metabolism*
  • Brain / pathology*
  • Brain / physiopathology
  • Brain Infarction / metabolism
  • Brain Infarction / physiopathology
  • Brain Ischemia / metabolism*
  • Brain Ischemia / physiopathology
  • Cell Communication / physiology
  • Chronic Disease
  • Connexin 43 / metabolism*
  • Female
  • Gap Junctions / metabolism*
  • Humans
  • Immunohistochemistry
  • Male
  • Models, Neurological
  • Neoplasms / complications
  • Neoplasms / metabolism
  • Neoplasms / physiopathology
  • Pneumonia / complications
  • Pneumonia / metabolism
  • Pneumonia / physiopathology
  • Up-Regulation / physiology

Substances

  • Connexin 43