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脑源性神经营养因子在腹外侧导水管周围灰质中的过度表达调节癫痫偏头痛共患病大鼠的行为。

Overexpression of BDNF in the ventrolateral periaqueductal gray regulates the behavior of epilepsy-migraine comorbid rats.

机构信息

Department of Neurology, The Second People's Hospital of Hefei, Hefei, China.

Department of Neurology, The First Affiliated Hospital of Anhui Medical University, Hefei, China.

出版信息

Brain Behav. 2022 Jun;12(6):e2594. doi: 10.1002/brb3.2594. Epub 2022 May 12.

DOI:10.1002/brb3.2594
PMID:35557046
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9226826/
Abstract

OBJECTIVE

To investigate the effects of brain-derived neurotrophic factor (BDNF) overexpression in the ventrolateral periaqueductal gray (vlPAG) on behavioral changes in epilepsy-migraine comorbid rats.

METHOD

We used an adeno-associated virus (AAV)-mediated vector to supplement BDNF in the vlPAG area prior to the establishment of a pilocarpine-nitroglycerin (Pilo-NTG) combination-induced comorbid model of epilepsy and migraine. Seizure- and migraine-related behaviors were analyzed. Cell loss and apoptosis in vlPAG were detected through hematoxylin-eosin (HE) and TUNEL staining. Immunofluorescence staining analyses were employed to detect expressions of BDNF and its receptor, tyrosine kinase B (TrkB), in vlPAG. Immunohistochemical staining was conducted to detect expressions of c-Fos and calcitonin gene-related peptide (CGRP) in the trigeminal nucleus caudalis (TNC) and trigeminal ganglion (TG).

RESULTS

Comparing to control group, AAV-BDNF injected comorbid group showed lower pain sensitivity, scratching head, and spontaneous seizures accompanied by the downregulation of c-Fos labeling neurons and CGRP immunoreactivity in the TNC and TG. However, these changes were still significantly higher in the comorbid group than those in both epilepsy and migraine groups under the same intervention.

CONCLUSION

These data demonstrated that supplying BDNF to vlPAG may protect structural and functional abnormalities in vlPAG and provide an antiepileptic and analgesic therapy.

摘要

目的

研究脑源性神经营养因子（BDNF）在腹外侧导水管周围灰质（vlPAG）中的过表达对癫痫-偏头痛共患病大鼠行为变化的影响。

方法

我们使用腺相关病毒（AAV）介导的载体在匹罗卡品-硝酸甘油（Pilo-NTG）联合诱导的癫痫和偏头痛共患病模型建立之前，补充 vlPAG 区域的 BDNF。分析癫痫发作和偏头痛相关行为。通过苏木精-伊红（HE）和 TUNEL 染色检测 vlPAG 中的细胞丢失和细胞凋亡。免疫荧光染色分析用于检测 vlPAG 中 BDNF 及其受体酪氨酸激酶 B（TrkB）的表达。免疫组织化学染色检测三叉神经尾核（TNC）和三叉神经节（TG）中 c-Fos 和降钙素基因相关肽（CGRP）的表达。

结果

与对照组相比，AAV-BDNF 注射共患病组的疼痛敏感性降低，出现搔抓头部和自发性癫痫，同时 TNC 和 TG 中的 c-Fos 标记神经元和 CGRP 免疫反应性下调。然而，与同一干预措施下的癫痫和偏头痛组相比，共患病组的这些变化仍然明显更高。

结论

这些数据表明，向 vlPAG 提供 BDNF 可能会保护 vlPAG 中的结构和功能异常，并提供抗癫痫和镇痛治疗。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5bd6/9226826/6499a2a85231/BRB3-12-e2594-g001.jpg
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