Molecules and Cells

Korean Society for Molecular and Cellular Biology (한국분자세포생물학회)
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Astrogliosis Is a Possible Player in Preventing Delayed Neuronal Death

  • Jeong, Hey-Kyeong (Department of Pharmacology, Ajou University School of Medicine) ;
  • Ji, Kyung-Min (Department of Pharmacology, Ajou University School of Medicine) ;
  • Min, Kyoung-Jin (Department of Pharmacology, Ajou University School of Medicine) ;
  • Choi, Insup (Department of Pharmacology, Ajou University School of Medicine) ;
  • Choi, Dong-Joo (Department of Pharmacology, Ajou University School of Medicine) ;
  • Jou, Ilo (Department of Pharmacology, Ajou University School of Medicine) ;
  • Joe, Eun-Hye (Department of Pharmacology, Ajou University School of Medicine)
  • Received : 2014.02.26
  • Accepted : 2014.03.28
  • Published : 2014.04.30
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Abstract

Mitigating secondary delayed neuronal injury has been a therapeutic strategy for minimizing neurological symptoms after several types of brain injury. Interestingly, secondary neuronal loss appeared to be closely related to functional loss and/or death of astrocytes. In the brain damage induced by agonists of two glutamate receptors, N-ethyl-D-aspartic acid (NMDA) and kainic acid (KA), NMDA induced neuronal death within 3 h, but did not increase further thereafter. However, in the KA-injected brain, neuronal death was not obviously detectable even at injection sites at 3 h, but extensively increased to encompass the entire hemisphere at 7 days. Brain inflammation, a possible cause of secondary neuronal damage, showed little differences between the two models. Importantly, however, astrocyte behavior was completely different. In the NMDA-injected cortex, the loss of glial fibrillary acidic protein-expressing ($GFAP^+$) astrocytes was confined to the injection site until 7 days after the injection, and astrocytes around the damage sites showed extensive gliosis and appeared to isolate the damage sites. In contrast, in the KA-injected brain, $GFAP^+$ astrocytes, like neurons, slowly, but progressively, disappeared across the entire hemisphere. Other markers of astrocytes, including $S100{\beta}$, glutamate transporter EAAT2, the potassium channel Kir4.1 and glutamine synthase, showed patterns similar to that of GFAP in both NMDA- and KA-injected cortexes. More importantly, astrocyte disappearance and/or functional loss preceded neuronal death in the KA-injected brain. Taken together, these results suggest that loss of astrocyte support to neurons may be a critical cause of delayed neuronal death in the injured brain.

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References

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