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Hyperglycemia increased brain ischemia injury through extracellular signal-regulated protein Kinase

Jian-Zhong Zhang1, Li Jing, Ai-Ling Ma

  • 1Institute of Immunopathology, School of Life Science & Technology, Xi'an Jiaotong University, Xi'an 710061, China. zhangjz@nxmc.edu.cn

Pathology, Research and Practice
|December 14, 2005
PubMed

Insights

Hyperglycemia worsens brain damage after stroke by increasing extracellular signal-regulated kinase (ERK) phosphorylation. Inhibiting ERK reduces this damage, suggesting ERK

Area of Science:

  • Neuroscience
  • Molecular Biology
  • Pathophysiology

Background:

  • Transient brain ischemia, a common stroke complication, can be exacerbated by hyperglycemia.
  • Mitogen-activated protein kinases (MAPKs), including Extracellular signal-regulated kinase (ERK), are implicated in cellular stress responses.

Purpose of the Study:

  • To investigate the role of ERK phosphorylation in transient brain ischemia under hyperglycemic conditions.
  • To elucidate the molecular mechanisms by which hyperglycemia worsens stroke-related brain damage.

Main Methods:

  • Global brain ischemia was induced in rats under normoglycemic (CIN) and hyperglycemic (CIH) conditions.
  • ERK phosphorylation was assessed using immunohistochemistry and Western blot analysis.
  • The effect of an ERK inhibitor (U0126) on neuronal survival was evaluated in hyperglycemic ischemic rats.

Main Results:

  • Increased phospho-ERK1/2 immunoreactive neurons were observed in the cingulate cortex and hippocampus after ischemia/reperfusion in both CIN and CIH groups.
  • Hyperglycemia (CIH) led to a significant increase in phospho-ERK1/2-positive neurons compared to normoglycemic conditions (CIN).
  • U0126 treatment significantly reduced phospho-ERK1/2 levels and immunoreactive cells in CIH rats, indicating ERK pathway involvement.

Conclusions:

  • ERK1/2 phosphorylation is upregulated during transient brain ischemia and significantly enhanced under hyperglycemic conditions.
  • Hyperglycemia exacerbates ischemic brain injury, at least partly, through increased ERK1/2 activation.
  • Targeting the ERK pathway may offer a therapeutic strategy to mitigate brain damage in stroke patients with hyperglycemia.

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