Abstract

A Feasibility Research on Restoration of Demyelination in Trigeminal Nerve with Transnasal Administration of BDNF/ NGF Loading on PEG-PLA Nanoparticles

Author(s): Lei Xia, Jun Zhong, Ming-Xing Liu, Ning-Ning Dou, Bin L

Abstract

Background

Trigeminal neuralgia (TN) is caused by the vascular compression of the Vth cranial nerve root, where the pathology of demyelination has been observed. Although microvascular decompression surgery has become the most reasonable technique for the treatment, this sort of operation is with risk and invasive. Accordingly, we attempt to find a noninvasive approach to treat TN.

Methods

Sprague Dawley (SD) rats were used for the experimental series. The brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) were used to restore the demyelization of trigeminal nerve, which were loading on poly (ethylene glycol)-poly (lactic acid) (PEG-PLA) nanoparticles. After nasal administration, then the nanoparticles were tracked with a vivo imaging system. The TN model was established by chronic constriction injury of the infraorbital nerve. Some rats that only underwent exposure of infraorbital nerve without ligation served as group sham. Those successful TN rats were randomly allocated to group TN+BDNF, group TN+NGF and group TN. After administration of BDNF-NPs and NGF-NPs as well as normal saline in different groups, then the mechanical allodynia was tested. Finally, all the animals were killed and the trigeminal nerve specimen was ready for electron microscopy, Western-Blotting, RT-PCR, CCK8 assay and immunostainingof S-100.

Results

The synthesized BDNF-NPs/NGF-NPs has a mean diameter and encapsulation efficiency of 129.8 nm/128.6 mm and 83.9%/79.5% with a release rate of 87.6%/85.3% (7 days later), respectively. The fluorescence signals of the nanoparticles appeared in the trigeminal nerve as early as 5 min, and became stronger at 30 min. Three weeks after the nasal administration, the mechanical allodynia didn’t change apparently in group Sham and group TN, while it significantly increased in group TN+BDNF and group TN+NGF. The microscopy exhibited that intact myelins with homogeneous density of axon in group TN+BDNF and group TN+NGF as well as in group sham, while the axons and myelin sheaths were absent in group TN. The results of Western-Blotting and RT-PCR indicated that the level of Nav1.8 and Bax were significantly increased in group TN compared with other groups (p<0.05). But the level of Bcl-2 and NF-κB were significantly increased in group TN+BDNF and TN+NGF compared with group TN (p<0.05). The CCK-8 and Immunostaining of S-100 experiments indicated that the BDNF-NPs or NGFNPs could promote the expression of Schwann cells (p<0.05).

Conclusions

The study demonstrated that BDNF/NGF loading on nanoparticles may transmit along with the trigeminal nerve via nasal administration and facilitate the restoration of myelin sheath. It could be a sort of noninvasive remedy for trigeminal neuralgia.


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