Previously
study has proved the non-erythropoietic mutant erythropoietin (MEPO)
exerted neuroprotective effects against ischemic cerebral injury, with
an efficacy similar to that of wild-type EPO. This study investigates
its effects on neurogenesis, angiogenesis, and gliogenesis in cerebral
ischemic mice. Male C57BL/6 mice were subjected to middle cerebral
artery occlusion (MCAO) and reperfusion. EPO (5000 U/kg), MEPO (5000
U/kg) or equal volume of normal saline was injected intraperitoneally.
Neurological function was evaluated by Rota-rod test, Neurological
severity scores (NSS) and Adhesive removal test. After ischemia and
reperfusion (I/R), the survival rate, brain tissue loss, neurogenesis,
angiogenesis and gliogenesis were detected by Nissl staining,
Immunofluorescence and Western blot, respectively. The results shown
that MEPO significantly increased survival rate, reduced brain tissue
loss, and improved neurological function after MCAO (P<0.05).
Furthermore, MEPO obviously enhanced the proliferation of neuronal
precursors (DCX) and promoted its differentiation into mature neurons
(NeuN) (P<0.05). In addition, compared to normal saline
treatment mice, MEPO increased the number of BrdU-positive cells in the
cerebral vasculature (P<0.05). Whereas, MEPO treatment also reduced the numbers of newly generated astrocytes (GFAP) and microglia (Iba1) (P<0.05).
Among all the tests in this study, there was no significant difference
between EPO group and MEPO group. Taken together, MEPO promoted the
regeneration of neurons and blood vessels in peripheral area of
infarction, and suppressed the gliogenesis, thus promoting neurogenesis,
improving neurological function and survival rate. Our findings suggest
that the MEPO may be a therapeutic drug for ischemic stroke
intervention.
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