ATP-binding cassette transporter A1 (ABCA1) plays an important role in the regulation of apolipoprotein E (ApoE) and the biogenesis of high-density lipoprotein (HDL) cholesterol in the mammalian brain. and oligodendrocyte maturation. Our data indicate that this ABCA1/ApoE/HDL signaling pathway contributes to myelination and oligodendrogenesis in the ischemic brain after stroke. 0.05, = 6/group). These data indicate that this deletion of brain ABCA1 reduces myelination in the WM of brain. Open in a separate window Physique 1 ATP-binding cassette transporter A1-deficient (ABCA1-B/-B) reduces myelination in the white matter (WM) of sham brain. (A,B) Electron microscopy (EM) images indicating the ultrastructure of WM in the corpus callosum (CC) from ABCA1-floxed ((B) sham brain. (CCE) Quantitative data of percentage of myelinated axons, myelin sheath thickness, and G ratio. Stars (*) Cisplatin represent of myelinated axon characteristically on the outside of the myelin sheath of axons; Pond (#) represents hypomyelinated with reduplicated basal lamina or non-myelinated axon with thin myelin or complete lack of myelin around axons; Yellow bar (-) represents myelin thickness. G ratio = % of axon diameter (a)/diameter of axon with myelin sheath (b). Scale bar = 800 nm. * 0.05, = 6/group. 2.2. ABCA1-B/-B Stroke Mice did not Exhibit Change in the Ischemic Lesion Volume but Show Decreased Functional Outcome Compared with ABCA1fl/f Stroke Mice; Administration of HDL3 or ApoE2 in ABCA1-B/-B Stroke Mice Attenuated ABCA1-B/-B-Induced Functional Deficits 14 and 21 Days after Stroke Assessment of infarct volume during the subacute stage post stroke overestimates true infarct volume because of edema . Our previous study showed that ABCA1-deficient (ABCA1-B/-B) mice exhibited a marginal increase (= 0.052) in lesion volume compared with ABCA1-floxed (ABCA1fl/fl) mice measured 7 days after stroke, with the lesion in ABCA1-B/-B stroke mice likely incorporating more BAM edema than the lesion in ABCA1fl/fl stroke mice. However, in the present study, there was no lesion volume change observed between ABCA1fl/fl and ABCA1-B/-B stroke mice administered cerebrospinal fluid (CSF), and within ABCA1-B/-B stroke mice administered CSF, HDL3, or ApoE2 21 days after stroke (Physique 2A, = 9/group). However, compared with ABCA1fl/fl stroke mice, the ABCA1-B/-B stroke mice exhibit significantly decreased neurological functional outcome from 3 Cisplatin to 21 days after stroke. The administration of HDL3 or ApoE2 into the ischemic brain of ABCA1-B/-B stroke mice starting 24 h and daily for 14 days significantly improve neurological functional outcome at 14 and 21 days after stroke (Physique 2B, 0.05, = 9/group). These data show that this administration of HDL3 or ApoE2 into the ischemic brain of reverses ABCA1-B/-B induced functional deficit after stroke. Open in a separate window Body 2 ABCA1-B/-B heart stroke mice considerably decreases useful outcome in comparison to ABCA1fl/fl heart stroke mice implemented with cerebrospinal liquid (CSF); administration of high-density lipoprotein (HDL)3 Cisplatin or apolipoprotein E (ApoE)2 in ABCA1-B/-B stroke mice advertises ABCA1-B/-B-induced useful deficit after stroke. (A) Quantitative data of lesion quantity. (B) Quantitative data from the adhesive removal check. * 0.05, vs. stroke mice; #, ^ 0.05, vs. stroke mice; = 9/group. 2.3. ABCA1-B/-B Reduced Myelination in the CC of Ischemic Boundary Area (IBZ) after Heart stroke; Administration of HDL3 or ApoE2 Attenuated the Deficits in the Myelination in the CC of IBZ in ABCA1-B/-B Heart stroke Mice To research the mechanism root how human brain ABCA1 deficiency reduces axonal myelination in the WM from the ischemic human brain after heart stroke and the way the administration of HDL3 and ApoE2 attenuate ABCA1-B/-B-induced decrease in myelination after heart stroke, the Cisplatin ultrastructural adjustments of WT in the CC of IBZ in the ipsilateral hemisphere had been measured. The info show the fact that myelination in the CC from the IBZ considerably reduced in ABCA1-B/-B stroke mice weighed against ABCA1fl/fl stroke mice 21 times after stroke. Nevertheless, the intracerebral infusion of ApoE2 or HDL3 not merely boosts myelination in ABCA1fl/fl heart stroke mice, it also considerably attenuates the decrease in the myelination in the CC of IBZ in ABCA1-B/-B heart stroke mice 21 times after heart stroke (Body 3ACC, = 6/group). These data suggest that ABCA1 deficit reduces myelination in the IBZ of WM, while ApoE2 or HDL3 treatment attenuates ABCA1-B/-B-induced deficits in the myelination of WM, which may donate to the neurological useful improvement after heart stroke. Open in another window Body 3 The electron microscopy (EM) pictures in the ischemic boundary.