ABSTRACT
Objective To observe the changes of intracerebral amino acid transmitters in the periventricular leukomalacia (PVL) of newborn rats with microdialysis and so as to explore the role of excitotoxicity in PVL.Methods Replicated the model for PVL at the age of postnatal day 5 (P5) by intracerebral injection of 3-nitropropionic acid (3-NPA).Before injection of 3-NPA,and 15 min,30 min,45 min,60 min,75 min,90 min after injection of 3-NPA,collected the sample of extracellular fluid (ECF) at the corpus callosum above the left ventricle through microdialysis,respectively.After microdialysis,the experimental rats were allowed to survive to P6-P14,and then they were killed and the brains were prepared for HE stain.The amino accids of dialysate were quantified through high performance liquid chromatography(HPLC),and then the excitotoxic index (EI) was calculated.Results Fifteen min to 45 min after injection of 3-NPA,the concentrations of glumate (Glu) and aspartic acid (Asp) of ECF elevated significantly,and then returned to the normal levels.Fifteen min to 75 min and 15 min to 30 min after injection of 3-NPA,the concentrations of glycine (Gly) and GABA significantly elevated,respectively,and returned to normal levels at 90 min and 45 min after injection of 3-NPA,respectively.But the EI,which indicated the balance of excitatory amino acids(EAAs) and inhibitory amno aciols(IAAs),significantly elevated 15 min to 75 min after injection of 3-NPA,then retured to normal level after 90 min.Sub-cortical and periventricular white matter rarefaction and significant lateral ventricle enlargement were observed in HE staining.Conclusions Changes of intracerebral amino acid transmitters in the PVL of newborn rats show regularity:EAAs,IAAs of ECF and EI elavate in the early stage,and then return to the normal level quickly.It indicates that excitotoxicity play a great role in PVL,especially at the early stage.Therefore,the preventions of PVL must be executed at the early stage.