Journal of Molecular Neuroscience

, Volume 21, Issue 2, pp 111–120 | Cite as

Hypertonicity promotes survival of corticospinal motoneurons via mitogen-activated protein kinase p38 signaling

  • Heidi Junger
  • David B. Edelman
  • Wolfgang G. Junger
Original Article


Extracellular hypertonicity can induce the phosphorylation of mitogen-activated protein kinases (MAPKs). Of these, both extracellular signal-regulated kinases (ERKs) and the stress-activated kinase p38 have been implicated in neuronal cell survival. Resuscitation with hypertonic saline decreases secondary brain injury after trauma, as well as neuronal damage, after ischemia. Since hypertonicity has been shown to support somatic cell survival, we investigated if hypertonicity can also prevent neuronal cell death via MAPK signaling. Death of postnatal rat corticospinal motoneurons (CSMNs) was induced by serum deprivation, and survival in both isotonic and hypertonic media was assessed after 20 h. Addition of NaCl (4–250 mM) to isotonic medium significantly and dose dependently protected CSMN in enriched cultures, increasing cell survival by up to 70% over that in isotonic medium. This response was not restricted to NaCl; addition of KCl, choline chloride, and sucrose had similar effects on cell survival. In addition, hypertonicity supported the survival of pure CSMN populations, albeit with lower potency. In cortical cell suspensions, hypertonic NaCl (20–100 mM) increased basal phosphorylation of p38 and ERK. The activation of both MAPKs, which was induced by 40 mM NaCl, was transient. Cultivation of CSMNs in media containing the specific p38 inhibitor SB203580 abolished the protective effect of hypertonic NaCl, indicating a central role for p38. We therefore conclude that hypertonicity can prevent neuronal cell death via MAPK signaling.

Index Entries

Neonatal rat motor neuron apoptosis primary neuronal culture mitogen-activated protein kinases stress-activated protein kinases 


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Copyright information

© Humana Press Inc 2003

Authors and Affiliations

  • Heidi Junger
    • 1
  • David B. Edelman
    • 2
  • Wolfgang G. Junger
    • 3
  1. 1.Department of AnesthesiologyUniversity of California San DiegoLa Jolla
  2. 2.The Neurosciences InstituteSan Diego
  3. 3.Department of Surgery, Division of TraumaUniversity of California San DiegoSan Diego

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