title: Pretreatment with monosialoganglioside GM1 protects the brain of fetal sheep against hypoxic-ischemic injury without causing systemic compromise.
abstract: The purpose of this study was to determine whether prophylaxis with monosialoganglioside GM1 can protect the fetus from hypoxic-ischemic encephalopathy in utero. Because some protective strategies can compromise the fetus, the effect of GM1 treatment on metabolic status and blood pressure was also evaluated. Chronically instrumented near-term fetal sheep (119-133 d) were subjected to 30 min of severe cerebral ischemia. Six were given 30 mg/kg GM1 through the umbilical vein 2 h before insult followed by continuous infusion of 30 mg/kg/d over the next 60 h, and these were compared with seven vehicle-treated control sheep. The time course of electrocorticographic activity and cytotoxic edema within the parasagittal cortex were determined with real-time spectral analysis and continuous impedance measurements, respectively. Histologic outcome was assessed 72 h later. Pretreatment with GM1 improved recovery of primary edema, reduced the duration of epileptiform activity (15 +/- 2 versus 31 +/- 5 h; p < 0.05) and the magnitude of secondary edema (p < 0.05). At 72 h, histologic damage was reduced, particularly in the cortex (p < 0.05) and hippocampus (p < 0.01), and residual electrocorticographic activity was increased in the GM1-treated group (-5 +/- 1 versus -9 +/- 3 dB, p < 0.01). GM1 infusion did not alter arterial blood pressure or metabolic status. These results indicate that GM1 can protect the fetal brain against hypoxic-ischemic injury without causing hypotension or metabolic compromise.
authors.affiliation: Research Centre for Developmental Medicine and Biology, School of Medicine, University of Auckland, New Zealand.
authors.forename: W K
authors.initials: WK
authors.lastname: Tan
authors.forename: C E
authors.initials: CE
authors.lastname: Williams
authors.forename: A J
authors.initials: AJ
authors.lastname: Gunn
authors.forename: E C
authors.initials: EC
authors.lastname: Mallard
authors.forename: P D
authors.initials: PD
authors.lastname: Gluckman
mesh_terms: D000818:Animals; D001930:Brain Injuries / Q000503:physiopathology / Q000517:prevention & control*; D002545:Brain Ischemia / Q000188:drug therapy / Q000503:physiopathology; D004569:Electroencephalography; D005260:Female; D005311:Fetal Hypoxia / Q000188:drug therapy / Q000503:physiopathology; D005677:G(M1) Ganglioside / Q000494:pharmacology*; D005732:Gangliosides / Q000494:pharmacology*; D002534:Hypoxia, Brain / Q000188:drug therapy / Q000503:physiopathology; D011247:Pregnancy; D015427:Reperfusion Injury / Q000503:physiopathology / Q000517:prevention & control; D012756:Sheep
chemical_list: D005732:Gangliosides; C025447:sialogangliosides; D005677:G(M1) Ganglioside