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在慢性三叉神经痛大鼠模型中，重复炎症性硬脑膜刺激后，血脑屏障出现区域性破坏。

Region-specific disruption of the blood-brain barrier following repeated inflammatory dural stimulation in a rat model of chronic trigeminal allodynia.

机构信息

1 Thomas Jefferson University, Department of Neurology, Philadelphia, PA, USA.

2 Thomas Jefferson University, Department of Neurosurgery, Philadelphia, PA, USA.

出版信息

Cephalalgia. 2018 Apr;38(4):674-689. doi: 10.1177/0333102417703764. Epub 2017 Apr 29.

DOI:10.1177/0333102417703764
PMID:28457145
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5762427/
Abstract

Background The blood-brain barrier (BBB) has been hypothesized to play a role in migraine since the late 1970s. Despite this, limited investigation of the BBB in migraine has been conducted. We used the inflammatory soup rat model of trigeminal allodynia, which closely mimics chronic migraine, to determine the impact of repeated dural inflammatory stimulation on BBB permeability. Methods The sodium fluorescein BBB permeability assay was used in multiple brain regions (trigeminal nucleus caudalis (TNC), periaqueductal grey, frontal cortex, sub-cortex, and cortex directly below the area of dural activation) during the episodic and chronic stages of repeated inflammatory dural stimulation. Glial activation was assessed in the TNC via GFAP and OX42 immunoreactivity. Minocycline was tested for its ability to prevent BBB disruption and trigeminal sensitivity. Results No astrocyte or microglial activation was found during the episodic stage, but BBB permeability and trigeminal sensitivity were increased. Astrocyte and microglial activation, BBB permeability, and trigeminal sensitivity were increased during the chronic stage. These changes were only found in the TNC. Minocycline treatment prevented BBB permeability modulation and trigeminal sensitivity during the episodic and chronic stages. Discussion Modulation of BBB permeability occurs centrally within the TNC following repeated dural inflammatory stimulation and may play a role in migraine.

摘要

背景

自 20 世纪 70 年代末以来，人们一直假设血脑屏障（BBB）在偏头痛中起作用。尽管如此，对偏头痛中 BBB 的研究仍很有限。我们使用三叉神经痛觉过敏的炎症汤大鼠模型，该模型非常类似于慢性偏头痛，以确定反复硬膜内炎症刺激对 BBB 通透性的影响。

方法

在发作期和慢性期，多次硬膜内炎症刺激期间，使用钠荧光素 BBB 通透性测定法在多个脑区（三叉神经尾核（TNC）、导水管周围灰质、额皮质、皮质下区和直接在硬膜激活区域下方的皮质）中测定 BBB 通透性。通过 GFAP 和 OX42 免疫反应性评估 TNC 中的神经胶质激活。测试米诺环素预防 BBB 破坏和三叉神经敏感性的能力。

结果

在发作期未发现星形胶质细胞或小胶质细胞激活，但 BBB 通透性和三叉神经敏感性增加。在慢性期，星形胶质细胞和小胶质细胞激活、BBB 通透性和三叉神经敏感性增加。这些变化仅在 TNC 中发现。米诺环素治疗可预防发作期和慢性期 BBB 通透性调节和三叉神经敏感性。

讨论

在反复硬膜内炎症刺激后，TNC 内的 BBB 通透性调节可能在偏头痛中起作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1d02/5762427/f9af4ceb85db/nihms929615f8.jpg
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