Neuroprotective effect of inhaled nitric oxide on excitotoxic-induced brain damage in neonatal rat.
BACKGROUND
Inhaled nitric oxide (iNO) is one of the most promising therapies used in neonates. However, little information is known about its impact on the developing brain submitted to excitotoxic challenge.


RESULTS
We investigated here the effect of iNO in a neonatal model of excitotoxic brain lesions. Rat pups and their dams were placed in a chamber containing 20 ppm NO during the first week of life. At postnatal day (P)5, rat pups were submitted to intracranial injection of glutamate agonists. At P10, rat pups exposed to iNO exhibited a significant decrease of lesion size in both the white matter and cortical plate compared to controls. Microglia activation and astrogliosis were found significantly decreased in NO-exposed animals. This neuroprotective effect was associated with a significant decrease of several glutamate receptor subunits expression at P5. iNO was associated with an early (P1) downregulation of pCREB/pAkt expression and induced an increase in pAkt protein concentration in response to excitotoxic challenge (P7).


CONCLUSIONS
This study is the first describe and investigate the neuroprotective effect of iNO in neonatal excitotoxic-induced brain damage. This effect may be mediated through CREB pathway and subsequent modulation of glutamate receptor subunits expression.
INSERM, Hôpital Robert Debré, Paris, France.
Julien
J
Pansiot
Gauthier
G
Loron
Paul
P
Olivier
Romain
R
Fontaine
Christiane
C
Charriaut-Marlangue
Jean-Christophe
JC
Mercier
Pierre
P
Gressens
Olivier
O
Baud
D000280:Administration, Inhalation; D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000187:drug effects*; D009682:Magnetic Resonance Spectroscopy; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000494:pharmacology*; D009569:Nitric Oxide / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats
D018696:Neuroprotective Agents; D009569:Nitric Oxide