g(m1)-ganglioside and Hypoxia-Ischemia--Brain

To explore the effect and safety of mild hypothermia therapy combined with monosialotetrahexosylganglioside (GM1) on neural function recovery of neonatal asphyxia complicated by hypoxic ischemic encephalopathy (HIE).. The clinical data of 90 neonates with HIE were retrospectively analyzed. According to the treatment methods, the neonates were divided into a routine group, a mild hypothermia group, and a combination group, with 30 cases in each group. The differences in neural function recovery, biochemical indexes, clinical signs recovery, efficacy, and complications were observed in the three groups after treatment.. After treatment, the score of neonatal behavioral neurological assessment (NBNA) and level of superoxide dismutase (SOD) in the combination group were higher than those of the other two groups (. Mild hypothermia therapy combined with GM1 for the treatment of neonatal asphyxia complicated by HIE can promote the recovery of neural function and reduce the incidence of complications in neonates.

Topics: Asphyxia Neonatorum; Biomarkers; Combined Modality Therapy; Computational Biology; Female; G(M1) Ganglioside; Humans; Hypothermia, Induced; Hypoxia-Ischemia, Brain; Infant, Newborn; Male; Neuropeptide Y; Phosphopyruvate Hydratase; Recovery of Function; Retrospective Studies; S100 Calcium Binding Protein beta Subunit; Safety; Superoxide Dismutase

Hypoxia/ischemia (HI) brain injury is a common central nervous system insult in newborns. Studies have demonstrated bioactivity of ginsenoside Rg1 in increasing neural viability and promoting angiogenesis. However, there are few reports on roles of Rg1 in brain repair of neonatal HI, and the mechanisms involved are unclear.. a neonatal HI model was established by a modified Rice-Vannucci model (RVM) and pups received ginsenoside Rg1 or monosialotetrahexosyl ganglioside (GM1) treatment. Neurological function and pathologic damage of rats were evaluated. Cellular apoptosis was detected with Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay. Immunohistochemistry for von willebrand factor (vwf) was used to label micro vessels. Expression levels of hypoxia-inducible factor-1α (HIF-1α), vascular endothelial growth factor (VEGF), and cleaved caspase 3 (CC3) were detected by western blot.. Both Rg1 and GM1 reduced neurological impairment and pathologic damage after HI by enhancing neural survival. Rg1, but not GM1, could also facilitate angiogenesis after HI. These pharmacological effects of Rg1 may be attributed to regulation of expression level of VEGF and CC3 and HIF-1α signaling pathway was involved.. Rg1 plays a neuroprotective role in brain repair following neonatal HI, and HIF-1α is a potential target for therapeutic intervention in neonates with HI brain injury.

Topics: Animals; Animals, Newborn; Apoptosis; Brain Injuries; Caspase 3; Disease Models, Animal; Female; G(M1) Ganglioside; Ginsenosides; Hypoxia-Inducible Factor 1, alpha Subunit; Hypoxia-Ischemia, Brain; Male; Neovascularization, Physiologic; Neurons; Neuroprotective Agents; Rats; Rats, Sprague-Dawley; Signal Transduction; Vascular Endothelial Growth Factor A

White matter injury characterized by damage to myelin is an important process in hypoxic-ischemic brain damage (HIBD). Because the oligodendrocyte-specific isoform of neurofascin, neurofascin 155 (NF155), and its association with lipid rafts are essential for the establishment and stabilization of the paranodal junction, which is required for tight interaction between myelin and axons, we analyzed the effect of monosialotetrahexosyl ganglioside (GM1) on NF155 expression and its association with lipid rafts after HIBD in Sprague-Dawley rats, weighing 12-15 g, on day 7 post-partum (P7; N = 20 per group). HIBD was induced on P7 and the rats were divided into two groups: one group received an intraperitoneal injection of 50 mg/kg GM1 three times and the other group an injection of saline. There was also a group of 20 sham-operated rats. After sacrifice, the brains of the rats were removed on P30 and studied by immunochemistry, SDS-PAGE, Western blot analysis, and electron microscopy. Staining showed that the saline group had definite rarefaction and fragmentation of brain myelin sheaths, whereas the GM1 group had no obvious structural changes. The GM1 group had 1.9-2.9-fold more GM1 in lipid rafts than the saline group (fraction 3-6; all P < 0.05) and 0.5-2.4-fold higher expression of NF155 in lipid rafts (fraction 3-5; all P < 0.05). Injection of GM1 increased the content of GM1 in lipid rafts as well as NF155 expression and its lipid raft association in HIBD rat brains. GM1 may repair the structure of lipid rafts, promote the association of NF155 (or other important proteins) with lipid rafts, stabilize the structure of paranodes, and eventually prevent myelin sheath damage, suggesting a novel mechanism for its neuroprotective properties.

Topics: Animals; Animals, Newborn; Blotting, Western; Brain; Cell Adhesion Molecules; Female; G(M1) Ganglioside; Hypoxia-Ischemia, Brain; Injections, Intraperitoneal; Male; Membrane Lipids; Microscopy, Electron; Myelin Sheath; Nerve Growth Factors; Random Allocation; Rats; Rats, Sprague-Dawley

Study the effect of ephedrine on neural plasticity of hypoxic ischemic brain damaged (HIBD) in neonatal rats, and explore the underlying molecular mechanism.. 60 Sprats suffered from HIBD (7 days old) were randomly divided into ephedrine group, D-amphetamine (D-AMPH) group, cytidine triphosphate (CTP) group, ganglioside (GM1) group, and spontaneous recovery group. Using immunohistochemical method to test the expression of growth-associated protein-43(GAP-43) and synaptophysin (SYP) on one side of hippocampal CA3 area, then, 4 weeks later, Morris Water Maze test was performed for five days.. (1) The expression levels of GAP-43 and SYP on hippocampal CA3 area in ephedrine group were higher than that in spontaneous recovery group (P<0.05). However, there was no statistical difference in ephedrine groups, CTP group, and D-AMPH group. (2) The average time of escape latency was significantly shorter in treating groups than that in spontaneous recovery group (P<0.05), and the frequency of original platform passing was higher than that in spontaneous recovery group (P<0.01). The average time of escape latency was longer in ephedrine group than that in GM1 group. The frequency of original platform passing was significantly less in ephedrine group than that in GM1 group, No statistical difference found in ephedrine groups, CTP group, and D-AMPH group.. Ephedrine may enhance memory, the abilities of spatial orientation and learning in HIBD rats. This protective effect may be associated with increasing synaptic connectivity, as assessed by increased expression of GAP-43 and SYP after HIBD. Ephedrine triggered similar protection against HIBD as treatment of D-AMPH and CTP. However, the amelioration of ability of spatial orientation, learning and memory by ephedrine on HIBD rats in later stage is slightly weaker than that by GM1, which may be related with ephedrine dosage.

Topics: Amphetamine; Animals; Animals, Newborn; Behavior, Animal; Central Nervous System Stimulants; Ephedrine; Female; G(M1) Ganglioside; GAP-43 Protein; Gene Expression Regulation; Hypoxia-Ischemia, Brain; Male; Maze Learning; Neuronal Plasticity; Pyrophosphatases; Random Allocation; Rats; Rats, Sprague-Dawley; Synaptophysin; Time Factors