Abstract

Excitotoxicity is a key molecular mechanism of perinatal brain damage and is associated with cerebral palsy and long term cognitive deficits. VIP induces a potent neuroprotection against perinatal excitotoxic white matter damage. VIP does not prevent the initial appearance of white matter lesion but promotes a secondary repair with axonal regrowth. This plasticity mechanism involves an atypical VPAC2 receptor and BDNF production. Stable VIP agonists mimic VIP effects when given systemically and exhibit a large therapeutic window. Unraveling cellular and molecular targets of VIP effects against perinatal white matter lesions could provide a more general rationale to understand the neuroprotection of the developing white matter against excitotoxic insults.

Keywords: Neuroprotection, cerebral palsy, plasticity, preterm infant, VPAC receptor, NAP, excitotoxicity, perinatal, multifactorial, ionotropic, phosphoinositide, cytoarchitectonic, astrocytic, murine, dysgeneses, isoleucine, forskolin, calmodulin, heterodimers, endopeptidases, methionine