Preparation of sustained-release microspheres of the brain-derived neurotrophic factor and its repairing effects on hypoxic-ischemic brain damage in rat via TrkB/CREB
10.3760/cma.j.cn121382-20240407-00504
- VernacularTitle:脑源性神经营养因子缓释微球的制备及其通过TrkB/CREB对大鼠缺血缺氧性脑损伤的修复作用
- Author:
Ying YANG
1
;
Qiong ZHOU
;
Lu TIAN
;
Fei HAN
;
Qianru YANG
Author Information
1. 西安国际医学中心医院脑科医院神经内科，西安 710000
- Keywords:
Brain-derived neurotrophic factor;
Hypoxic-ischemic brain damage;
Sustained-release microsphere;
Tyrosine receptor kinase B;
cAMP-response element binding
- From:
International Journal of Biomedical Engineering
2024;47(5):436-441
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate the preparation of sustained-release microspheres of brain-derived neurotrophic factor (BDNF) and its repairing effects on hypoxic-ischemic brain damage as well as the regulation of the tyrosine receptor kinase B (TrkB)/cAMP-response element binding protein (CREB) pathway in rats.Methods:BDNF sustained-release microspheres were prepared by emulsification-solvent evaporation method and polymer alloying method. The morphology of the microspheres was observed by a transmission electron microscope. The particle size and Zeta potential of the microspheres were measured by a Malvern ZS90 particle size analyzer, and the encapsulation rate and plasmid loading of the BDNF sustained-release microspheres were determined. The sustained release of the microspheres in vitro was also detected. A total of 45 SD rats were randomly divided into the sham-operation group, the model group, and the treatment group, with 15 rats in each group. Except for the sham-operation group, ischemic-hypoxic brain injury models were established in the other two groups by ligating the right common carotid artery and in a hypoxia environment. The rats in the treatment group were injected with 100 mg/kg of BNDF sustained-release microsphere solution via the tail vein once a day for 4 weeks, while the rats in the sham-operation group and the model group were injected with an equal amount of blank microsphere solution via the tail vein. At the end of the intervention, the neurological function scores, brain tissue water content, cerebral infarction area, malondialdehyde (MDA), and superoxide dismutase (SOD) levels were measured. The levels of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) were detected by enzyme-linked immunosorbent assay (ELISA). The protein expressions of BDNF, TrkB, and phosphorylated CREB (p-CREB) were detected by Western Blot. Results:The appearance of BDNF sustained-release microspheres was round or oval, with a smooth surface and uniform size distribution. No interfused microspheres were observed. The size of microspheres was (221.49 ± 5.75) nm, the Zeta potential was (?27.03 ± 4.22) mV, and the encapsulation rate was (80 ± 2) %. The microspheres (1 mg) could carry (1.55 ± 0.04) μg of BDNF plasmid, and the sustained release of the drug stabilized at day 28. Compared with the model group, the neurological function score, brain tissue water content, cerebral infarction area, MDA, TNF-α, and IL-6 levels were decreased, and the SOD level and the protein expression of BDNF, TrkB, and p-CREB were increased in the treatment group (all P < 0.05). Conclusions:BDNF sustained-release microspheres can promote the repair of neurological damage caused by cerebral ischemia and hypoxia, reduce inflammation response and oxidative stress, and alleviate cerebral edema and cerebral infarction, which may play a role by activating the BDNF/TrkB/CREB pathway.
