Increased p38 mitogen-activated protein kinase signaling is involved in the oxidative stress associated with oxygen and glucose deprivation in neonatal hippocampal slice cultures

Qing Lu, Thomas F. Rau, Valerie Harris, Maribeth H Johnson, David J. Poulsen, Stephen Matthew Black

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

The pathological basis of neonatal hypoxia-ischemia (HI) brain damage is characterized by neuronal cell loss. Oxidative stress is thought to be one of the main causes of HI-induced neuronal cell death. The p38 mitogen-activated protein kinase (MAPK) is activated under conditions of cell stress. However, its pathogenic role in regulating the oxidative stress associated with HI injury in the brain is not well understood. Thus, this study was conducted to examine the role of p38 MAPK signaling in neonatal HI brain injury using neonatal rat hippocampal slice cultures exposed to oxygen/glucose deprivation (OGD). Our results indicate that OGD led to a transient increase in p38 MAPK activation that preceded increases in superoxide generation and neuronal death. This increase in neuronal cell death correlated with an increase in the activation of caspase-3 and the appearance of apoptotic neuronal cells. Pre-treatment of slice cultures with the p38 MAPK inhibitor, SB203580, or the expression of an antisense p38 MAPK construct only in neuronal cells, through a SynapsinI-1-driven adeno-associated virus vector, inhibited p38 MAPK activity and exerted a neuroprotective effect as demonstrated by decreases in OGD-mediated oxidative stress, caspase activation and neuronal cell death. Thus, we conclude that the activation of p38 MAPK in neuronal cells plays a key role in the oxidative stress and neuronal cell death associated with OGD.

Original languageEnglish (US)
Pages (from-to)1093-1101
Number of pages9
JournalEuropean Journal of Neuroscience
Volume34
Issue number7
DOIs
StatePublished - Oct 1 2011

Fingerprint

p38 Mitogen-Activated Protein Kinases
Oxidative Stress
Oxygen
Glucose
Cell Death
Ischemia
Brain Injuries
Brain Hypoxia-Ischemia
Dependovirus
Neuroprotective Agents
Protein Kinase Inhibitors
Caspases
Superoxides
Caspase 3
Hypoxia

Keywords

  • Apoptosis
  • Hypoxia-ischemia
  • Neonate brain
  • Neuronal cell death
  • Rat
  • Superoxide

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Increased p38 mitogen-activated protein kinase signaling is involved in the oxidative stress associated with oxygen and glucose deprivation in neonatal hippocampal slice cultures. / Lu, Qing; Rau, Thomas F.; Harris, Valerie; Johnson, Maribeth H; Poulsen, David J.; Black, Stephen Matthew.

In: European Journal of Neuroscience, Vol. 34, No. 7, 01.10.2011, p. 1093-1101.

Research output: Contribution to journalArticle

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