Amelioration by glycine of brain damage in neonatal rat brain following hypoxia–ischemia

Background Glycine protected adult brains against injury in an experimental model of stroke. However, because the ischemic response of neonatal brains differs from that of adult brains, we examined the neuroprotective efficacy of glycine and associated mechanisms in an experimental model of neonatal hypoxic−ischemic (HI) encephalopathy. Methods Neonatal (P7) Wister rats were randomly divided into an untreated group (non-HI) and two HI groups that were treated with left common carotid artery ligation and saline control or glycine. After recovery, pups that received surgery were injected intraperitoneally with saline or glycine (800 mg/kg, the optimal dose determined in pilot experiments) and were placed in a controlled 8% O2 chamber for 120 min. Brains were harvested at various times after return to normoxia (several hours to days post-HI) for analyses of infarct areas, glial activation, cell apoptosis, and tumor necrosis factor alpha (TNFα) expression using histology and RT-PCR. Results Glycine injections induced large (~15-fold) but brief (~2-h) increases in cerebrospinal fluid concentrations. In particular, the glycine group exhibited a > 70% decrease in infarct areas compared to controls at 7 days post-HI. Glycine also significantly reduced astrocyte reactive transformation, microglia activation, and TUNEL-positive (apoptotic) cell numbers in perilesional areas at 3 days post-HI, and TNFα mRNA expression in the injured hemisphere at 12 and 24 h post-HI. Conclusion Glycine protected neonatal rat brains against HI, in part by inhibiting TNFα-induced inflammation and gliosis. Hence, systemic glycine infusions may have clinical utility for the treatment of HI injury in human newborns. This article is protected by copyright. All rights reserved.