Objective To investigate the comparative neuroprotective effects of human umbilical cord mesenchymal stem cells (hUC-MSCs-Exos) administered via different routes on hypoxic ischemic brain damage (HIBD) in neonatal mice. Methods Healthy one-week-old SPF-grade BALB/c mice were randomly divided into 4 groups: sham operation group (n=6), model group (n=6), exosome group 1 (n=8), exosome group 2 (n=8). HIBD was induced using the Rice-Vannucci method. Exosome group 1 and Exosome group 2 were intraperitoneal injection/intranasal drip of phosphate buffer (PBS) 100 μl containing 10 μl exosomes within 24 h after successful modeling, respectively. Sham operation and model groups were intraperitoneal injection of PBS 100 μl. On the 7th day after the intervention, neuromotor function was assessed using the horizontal grid test and pole climbing test. On the 2nd day after the evaluation, all mice were killed and their brains were removed by decapitation. HE staining was used to observe the pathological injury of brain tissue, toluidine blue staining was used to observe the survival of neurons in cerebral cortex, and TUNEL staining was used to observe the apoptosis of cerebral cortex cells. Results Compared with sham operation group, model group, exosome group 1 and exosome group 2 exhibited increased hind limb drops in horizontal grid test and climbing scores (P<0.05). No significant difference was found in model group, exosome group 1 and exosome group 2 in these measures (P<0.05). Significant pathology was observed in model group, exosome group 1 and exosome group 2 compared to sham operation group (P<0.05), with significantly reduced damage in exosome group 1 and exosome group 2 compared to model group (P<0.05). Compared with sham operation group, Nissl body count was lower in model group and exosome group 1 and exosome group 2, with a higher count in exosome group 2 compared to exosome group 1 (P<0.05). Compared with sham operation group, apoptotic cells were higher in model group and exosome group 1 and exosome group 2, with a significant reduction in exosome group 1 and exosome group 2 compared to model group, and the lowest in exosome group 2 (P<0.05). Conclusions hUC-MSCs-Exos can improve the neuronal motor function, promote neuron repair and inhibit apoptosis in HIBD mice. Intranasal administration of hUC-MSCs-Exos is more effective than intraperitoneal administration for reducing neuronal apoptosis in HIBP neonatal mice, offering a convenient and rapid method suitable for clinical application.
| 科 Family | 属数 Number of genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) | 属 Genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) |
|---|---|---|---|---|---|---|
| 鹅膏菌科Amanitaceae | 2 | 11 | 5.26 | 鹅膏菌属 Amanita | 10 | 4.78 |
| 小菇科 Mycenaceae | 2 | 12 | 5.74 | 丝盖伞属 Inocybe | 5 | 2.39 |
| 多孔菌科 Polyporaceae | 8 | 14 | 6.70 | 蜡蘑属 Laccaria | 5 | 2.39 |
| 红菇科 Russulaceae | 3 | 23 | 11.00 | 小皮伞属 Marasmius | 6 | 2.87 |
| 小菇属 Mycena | 11 | 5.26 | ||||
| 光柄菇属 Pluteus | 5 | 2.39 | ||||
| 红菇属 Russula | 17 | 8.13 | ||||
| 栓菌属 Trametes | 5 | 2.39 |