ABSTRACT
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.
Subject(s)
Animals , Female , Male , Rats , Cell Adhesion Molecules/metabolism , G(M1) Ganglioside/metabolism , G(M1) Ganglioside/pharmacology , Hypoxia-Ischemia, Brain/metabolism , Membrane Lipids/metabolism , Myelin Sheath/drug effects , Nerve Growth Factors/metabolism , Animals, Newborn , Blotting, Western , Brain/ultrastructure , Hypoxia-Ischemia, Brain/pathology , Injections, Intraperitoneal , Microscopy, Electron , Myelin Sheath/metabolism , Myelin Sheath/pathology , Random Allocation , Rats, Sprague-DawleyABSTRACT
After filariasis was basically controlled (the microfilarial rate was lower than 1%) in Henan Province in 1987, longitudinal observation of the disease has been carried out in all the province in order to study the regular pattern of growth and decline or the transmission potential of the disease. According to the distribution of filaria species and original microfilarial rate, 7 administrative villages in 7 counties were selected as surveillance sites. From 1988 to 1995, etiological and mosquito vector surveys were made continuously in all sites where no control measure was conducted. 10 surviving microfilaremic individuals became negative gradually over the first 6 years and no new microfilaremia was found. Since then, the microfilarial rate was zero. During the 8 years, 19 vector mosquitos were positive, with a total of 33 filarial larva. Culex pipiens pallens was the predominant mosquito species inside human dwelling in all sites. The man-biting rate of mosquitos for outdoor sleepers fluctuated greatly, the highest was 360.60 mosquitos per man per night and the lowest 7.20. The man-biting rate of mosquitos for sleepers inside mosquito-nets was approximately 1. The proportion of multiparous mosquitos also fluctuated greatly, the highest was 88.10% and the lowest 27.27%. According to the data described above, the man-biting rate of mosquitos which contained filaria L3 was less than 1 mosquito per man per transmission season. It is suggested that after the microfilarial rate was lower than 1%, the surviving microfilaremias became negative gradually in 3-5 years, and the transmission of the disease was blocked. Therefore, in the districts where filariasis was basically controlled, elimination of the disease was attainable.