proteomic analysis of neonatal mouse brain evidence for hypoxia and ischemiainduced dephosphorylation of collapsin response mediator proteins perinatal hypoxia and ischemia hi are a significant cause of mortality and morbidity to understand the molecular mechanisms for hiinduced brain damage here we used a proteomic approach to analyze the alteration and modification of proteins in neonatal mouse brain 24 h after hi treatment significant changes of collapsin response mediator proteins crmps were observed in hi brain crmps are a family of cytosolic proteins involved in axonal guidance and neuronal outgrowth we found that crmp2 crmp4 and crmp5 proteins were altered posttranslationally after hi treatment mass spectrometric and western blot analyses detected hypophosphorylated crmp proteins after hi further analysis of crmp kinases indicated inactivation of cyclin dependent kinase 5 cdk5 a priming kinase of crmps and a neuronal specific kinase that plays pivotal roles in neuronal development and survival the reduction of cdk5 activity was associated with underexpression of its activator p35 taken together our findings reveal hiinduced dephosphorylation of crmps in neonatal brain and suggest a novel mechanism for this modification hypophosphorylated crmps might be implicated in the pathogenesis of hirelated neurological disorders