Excitotoxicity may be critical in the formation of brain lesions associated with cerebral palsy. When injected into the murine neopallium at postnatal day (P) 5, ibotenate (activating NMDA and metabotropic glutamate receptors) produces neuronal death and white matter cysts. Such white matter cysts resemble those seen in periventricular leukomalacia, a lesion evident in numerous human premature newborns. The goal of this study was to assess BDNF neuroprotection against neonatal excitotoxic lesions. Cortical and white matter lesions induced by ibotenate at P5 were reduced by BDNF by up to 36 and 60%, respectively. BDNF neuroprotection involved TrkB receptors, MAPK pathway and reduced apoptosis. Although BDNF did not prevent the initial appearance of white matter lesions, it promoted secondary decrease of the lesion size. BDNF neuroprotection at P5 was maximal against lesions induced by NMDA or ibotenate but was moderate against lesions produced by an AMPA-kainate agonist. Finally, BDNF exacerbated neuronal death produced by ibotenate at P0 through increased apoptosis and p75(NTR) receptors, while BDNF had no detectable effect on lesions induced at P10. Altogether, these data showed that BDNF neuroprotection against neonatal excitotoxicity is dependent upon the type of activated glutamate receptors, the lesion localization and the developmental stage.

Neuromodulation, thanks to intrinsic and extrinsic brain feedback loops, seems to be the best way to exploit brain plasticity for therapeutic purposes. In the past years, there has been tremendous advances in the field of non-pharmacological modulation of brain activity. This review of different neurostimulation techniques will focus on sites and mechanisms of both transcutaneous vagus and trigeminal nerve stimulation. These methods are scientifically validated non-invasive bottom-up brain modulation techniques, easily implemented from the outer ear. In the light of this, auricles could transpire to be the most affordable target for non-invasive manipulation of central nervous system functions.

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