Vasoactive intestinal peptide prevents excitotoxic cell death in the murine developing brain

Pierre Gressens*, Stéphane Marret, Joanna M. Hill, Douglas E. Brenneman, Illana Gozes, Mati Fridkin, Philippe Evrard

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


Excitotoxic damage may ge a critical factor in the formation of brain lesions associated with cerebral palsy. When injected at birth, the glutamatergic analog ibotenate induces mouse brain lesions that strikingly mimic human microgyria. When ibotenate is injected at postnatal day 5, it produces transcortical necrosis and white matter cysts that mimic human perinatal hypoxic-like lesions. Vasoactive intestinal peptide (VIP) has potent growth-related actions and neuroprotective properties that influences mitosis and neuronal survival in culture. The goal of this study was to assess the protective role of VIP against excitotoxic lesions induced by ibotenate in developing mouse brain. VIP cotreatment reduced ibotenate- induced microgyric-like cortical lesions and white matter cysts by up to 77 and 85%, respectively. VIP protective effects were reproduced by a peptide derived from activity-dependent neurotrophic factor (ADNF), a trophic factor released by VIP-stimulated astrocytes, and by stearyl norleucine VIP, a specific VIP agonist that does not activate adenylate cyclase. Neither forskolin, an adenylate cyclase activator, nor pituitary adenylate cyclase- activating peptide, provided VIP-like protection. VIP and neurotrophic analogs, acting through a cAMP-independent mechanism and inducing ADNF release, could represent new avenues in the understanding and prevention of human cerebral palsy.

Original languageEnglish
Pages (from-to)390-397
Number of pages8
JournalJournal of Clinical Investigation
Issue number2
StatePublished - 15 Jul 1997


  • Activity-dependent neurotrophic factor
  • Cerebral palsy
  • Ibotenic acid
  • N- methyl-D-aspartate
  • Vasoactive intestinal peptide


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