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Objective To evaluate whether recombinant human erythropoietin (rh-EPO) could increase the angiogenic responses in preterm rat models with periventricular white matter damage (PWMD).Methods Three-day postnatal rats were divided into 3 groups randomly:the sham group,the hypoxic-ischemic (HI) group and the recombinant human erythropoietin(rh-EPO)treatment group.Rat pups underwent permanent ligation of the right common carotid artery followed by 60 mL/L O2 for 4 h or sham operation and normoxic exposure.Immediately after the HI,rats received a single intraperitoneal injection of rh-EPO (5 U/g)or saline.Angiogenesis-related cells (CD34 + cells),microvessel density (MVD)and arteriovenous related genes (ephrinB2 and EphB4)were examined at 48 h and 96 h after operation.Results At 48 h after operation,the proteins of CD34 in HI rats increased compared with the sham rats (HI group vs Sham group:0.54 ± 0.05 vs 0.42 ± 0.05,P ＜ 0.05).However,the MVD,the mRNA of ephrinB2 and EphB4 did not change (P ＞ 0.05).The proteins of CD34,the mRNA of ephrinB2 and EphB4 increased after rh-EPO treatment compared with HI rats.However,the MVD did not increase.As the proteins of CD34 increased further at 96 h after operation (HI group vs Sham group:0.85 ± 0.06 vs 0.62 ± 0.06,P ＜ 0.05),the MVD (3.14 ± 1.21 vs 1.50 ± 1.04),ephrinB2 (7.51 ± 1.89 vs 1.28 ± 0.24) and EphB4 (4.58 ± 0.82 vs 1.21 ± 0.22) also increased (all P ＜ 0.05).And the proteins of CD34 increased after administration of rh-EPO(EPO group vs HI group:0.98 ± 0.07 vs 0.85 ± 0.06,P ＜0.05) and MVD(EPO group vs HI group:4.71 ± 1.38 vs 3.14 ± 1.21,P ＜0.05) were increased after administration of rh-EPO.However,the ephrinB2 and EphB4 did not increased after administration of rh-EPO at 96h time point.Conclusion Endogenous regenerative response is triggered in the damaged tissues and rh-EPO increases the angiogenesis in model rats with PWMD.
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Objective To investigate the protective effect of melatonin and its possible mechanism for repairing in the immature white matter damage due to brain hypoxia-ischemia (HI).Methods Forty-eight three-day SD rats after birth were randomly divided into 3 groups:sham-operated(SHAM) group,HI group and melatonin treatment(MT) group.Periventricular white matter damage (PWMD) to animal models were estabished according to Rice modeling.MT group was treated with melatonin pre-operatively,immediately postoperation,1 hour postoperation and 24 hours postoperation via intraperitoneal injection,and the other groups were injected with the same volume of dissolvent.The rats were executed by decollation after 2 days and 14 days.The histological changes in periventricular white matter were observed by HE staining and immunohistochemistry.Results For the 3 groups,the structure in ope-ration side of the white matter in the peripheral ventricles of the brain 2 days postoperation were significant different (P ＜0.05).The O4 positive cells decreased one by one/greatest in the SHAM group[(75.548 ± 7.333)/hpf] followed by MT group [(59.971 ± 3.635)/hpf],and HI group [(40.511 ± 2.848)/hpf] (P ＜ 0.05).The expression of Casepase-3 increased in the SHAM group (107.724 ± 10.266),MT group (132.289 ± 8.537),and HI group (202.168 ± 14.367),and the difference was statically significant (P ＜ 0.05).Ventricular index was greater in operation side of the white matter in the peripheral ventricles of the 14-day-brain in the SHAM group(0.928 ±0.063),MT group (1.813 ± 0.110),HI group (2.752 ± 0.201),increasingly,while absorbance value of myelin basic protein decreased one by one in sequence(39.504 ± 1.673,21.729 ± 1.614,11.344 ± 1.118).Conclusions MT plays a role in protecting the periventricular white matter via inhibiting the apoptosis of oligodendrocyte progenitor cell,and thus benefits the PWMD.