Effect of minocycline on glutamate uptake in periventricular zone of neonatal rats after hypoxia

AIM: To investigate the role of minocycline on glutamate uptake in the periventricular zone and its putative mechanism after hypoxic exposure in neonatal rats. METHODS: A model of hypoxic-ischemic brain damage (HIBD) was developed by putting postnatal 1 d rat pups in 5% O₂ for 3.5 h. The glutamate level in periventricular zone was measured by liquid chromatography coupled with tandem mass spectrometry assay (LC-MS/MS) after hypoxic exposure for 4 h and 1 d. The dynamic changes of glutamate transporters EAAT1, and EAAT2 during developmental period in periventricular zone were determined by Western blot. Moreover, the expression of EAAT1, EAAT2, Iba-1, IL-1β, TNF-α and TGF-β1 was also detected by Western blot after hypoxic exposure for 4 h and 1 d in that region. The effects of minocycline on all parameters mentioned above were tested after minocycline treatment at the same time points and in the same region. RESULTS: After hypoxic exposure, glutamate level was increased, but it was decreased after minocycline treatment. EAAT1 and EAAT2 kept a low expression level at the first postnatal week, but a predominant elevation was found at the end of the second postnatal week. The expression of EAAT1, EAAT2, Iba-1, IL-1β and TGF-β1 was increased at 1 d after hypoxic exposure. EAAT1 and TNF-α expression was significantly up-regulated, while EAAT2 was down-regulated after minocycline treatment. CONCLUSION: Minocycline inhibits the increase in the glutamate level after hypoxia in periventricular region of the neonatal rats. The mechanism may relate to the selective regulation of glutamate transporters, rather than the inhibition of neuroinflammation in periventricular zone.