| Objective: To study the effects of neuregulin-1β(NRG-1β) on the white matter expression of tumor necrosis factor-α(TNF-α), infiltration of inflammatory cell, apoptosis of nerve cell, injury of oligodendrocytes, destruction and regeneration of myelin sheath after focal cerebral ischemia reperfusion and the related protective mechanism in rats.Methods: Intraluminal thread methods were applied to establish the middle cerebral artery occlusion reperfusion (MCAO/R) models in the rat; NRG-1β(2.5ng/kg) was given through lateral ventricle injection for treatment; the histopathologic changes of white matter were observed with hematoxylin-eosin (HE) staining. TNF-αcontent of white matter was detected by enzyme-linked immunosorbent assay (ELISA); expression and localization of myelin basic protein(MBP) were detected by immunohistochemistry staining; amount of apoptotic cells were marked with terminal deoxynucleotidyl transferase-mediated dUTP-biotin in situ nick end-labeling (TUNEL); the structural changes of oligodendrocytes and myelin sheaths were observed through transmission electron microscope.Results: The histopathologic changes of white matter can be observed with HE staining after focal cerebral ischemia reperfusion injury. Compared with sham group, the MCAO/R group showed higher TNF-αcontent, large number of inflammatory cell infiltration, poor nerve fibers, cystic degeneration, less MBP positive fibers, large number of apoptotic cells in the ischemia cerebral white matter after MCAO/R for 3ds, oncotic and apoptotic oligodendrocytes and demyelination were found in the ischemia cerebral white matter by transmission electron microscopy. In the control groups, compared with 3d reperfusion group, 7d reperfusion group had decrease in white matter inflammatory cell infiltration and apoptotic cells; decrease in TNF-αcontent, yet higher than sham group; deeper MBP staining in particular area, with higher density of MBP positive fibers; formation of new myelin sheathes were found by transmission electron microscopy. At time point of 3d and 7d, NRG-1βtreatment groups showed significantly improvement in the aforesaid indexes compared to the corresponding control groups.Conclusion: Distinct damages can be conduced to white matter by MCAO/R. NRG-1βlateral ventricle injection treatment has protective action on white matter of cerebral ischemia reperfusion. The mechanism is related to restraint of inflammatory reaction, apoptosis of oligodendrocytes and myelin sheath destruction, promotion of MBP synthesis and new myelin sheath formation. |
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