Molecular evidence of aquaporin-4 dysregulation and neuroinflammatory stress underlying blood-brain barrier dysfunction in idiopathic intracranial hypertension: A case-control study.

IF 3.9 2区 医学 Q1 CLINICAL NEUROLOGY
Headache Pub Date : 2026-10-08 DOI:10.1111/head.70232
Vaishali Sharma, Jitender Singh, Pramod Avti, Shiv Lal Soni, Aastha Takkar, Swapnajeet Sahoo, Sucharita Ray, Kamalesh Chakravarty
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Abstract

Objective: To evaluate aquaporins (AQP), heat shock proteins (HSP), and CD146 (cluster of differentiation) as molecular markers of blood-brain barrier (BBB) disruption and neuroinflammation in idiopathic intracranial hypertension (IIH).

Background: Emerging evidence implicates BBB dysfunction and neuroinflammation, yet their mechanistic basis in IIH is unclear.

Methods: In this case-control study with cross-sectional exposure ascertainment, conducted in Postgraduate Institute of Medical Education and Research, Chandigarh, India, from March 2023 to September 2024, newly diagnosed patients with IIH and age- and sex-matched healthy individuals undergoing spinal anesthesia for non-neurological disease anesthesia controls (AC) and age- and sex-matched healthy controls (HC) were enrolled. Protein levels of AQPs and gene expression of HSPs and CD146 were quantified in blood and cerebrospinal fluid (CSF) and correlated with clinical features and severity.

Results: Patients with IIH were predominantly female (87%), with mean body mass index (BMI) 28.1 ± 5.2 kg/m2 and mean CSF opening pressure 27.4 ± 4.8 cm CSF. Patients with IIH demonstrated reduced AQP4CSF levels as compared to AC group (2.65 [2.09, 3.70] vs. 3.07 [1.65, 7.15], p = 0.016) and increased gene expression of HSP70Blood as compared to AC and HC (3.86 [1.02, 5.61] vs. 1.08 [0.78, 2.91] vs. 1.77 [0.43, 2.27], p = 0.002); increased gene expression of HSP60CSF as compared to AC (1.28 [0.37, 2.44] vs. 0.52 [0.23, 1.26], p = 0.038); and increased gene expression of CD146Blood as compared to AC and HC (1.27 [0.50, 4.29] vs. 0.53 [0.35, 1.36] vs. 0.91 [0.58, 1.70], p = 0.008). HSP70CSF, HSP60Blood, and CD146Blood corelated positively with Headache Impact Test-6 (HIT-6) and MIDAS scores (ρ = 0.41, p = 0.01; ρ = 0.34, p = 0.032; ρ = 0.35, p = 0.029, ρ = 0.35) indicating an association with disease severity.

Conclusion: The findings provide molecular evidence of BBB disruption and neuroinflammatory pathway involved in the pathophysiology of IIH.

特发性颅内高压患者血脑屏障功能障碍的水通道蛋白-4失调和神经炎症应激的分子证据:一项病例对照研究。
目的:探讨水通道蛋白(AQP)、热休克蛋白(HSP)和CD146 (cluster of differentiation)作为特发性颅内高压(IIH)患者血脑屏障(BBB)破坏和神经炎症的分子标志物。背景:新出现的证据暗示血脑屏障功能障碍和神经炎症,但其在IIH中的机制基础尚不清楚。方法:本研究采用横断面暴露确定法,于2023年3月至2024年9月在印度昌迪加尔医学教育与研究研究生院开展,纳入了新诊断的IIH患者和年龄和性别匹配的健康个体,他们接受了非神经系统疾病麻醉对照组(AC)和年龄和性别匹配的健康对照组(HC)。定量血液和脑脊液中AQPs蛋白水平、HSPs和CD146基因表达,并与临床特征和严重程度相关。结果:IIH患者以女性为主(87%),平均体重指数(BMI) 28.1±5.2 kg/m2,平均脑脊液开口压27.4±4.8 cm CSF。IIH患者AQP4CSF水平低于AC组(2.65[2.09,3.70]比3.07 [1.65,7.15],p = 0.016), HSP70Blood基因表达高于AC和HC组(3.86[1.02,5.61]比1.08[0.78,2.91]比1.77 [0.43,2.27],p = 0.002);与AC相比,HSP60CSF基因表达增加(1.28[0.37,2.44]比0.52 [0.23,1.26],p = 0.038);CD146Blood基因表达增高(1.27 [0.50,4.29]vs. 0.53 [0.35, 1.36] vs. 0.91 [0.58, 1.70], p = 0.008)。HSP70CSF、HSP60Blood和CD146Blood与头痛冲击测试-6 (HIT-6)和MIDAS评分呈正相关(ρ = 0.41, p = 0.01; ρ = 0.34, p = 0.032; ρ = 0.35, p = 0.029, ρ = 0.35),表明与疾病严重程度相关。结论:本研究结果为血脑屏障破坏和神经炎症通路参与IIH的病理生理提供了分子证据。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Headache
Headache 医学-临床神经学
CiteScore
9.40
自引率
10.00%
发文量
172
审稿时长
3-8 weeks
期刊介绍: Headache publishes original articles on all aspects of head and face pain including communications on clinical and basic research, diagnosis and management, epidemiology, genetics, and pathophysiology of primary and secondary headaches, cranial neuralgias, and pains referred to the head and face. Monthly issues feature case reports, short communications, review articles, letters to the editor, and news items regarding AHS plus medicolegal and socioeconomic aspects of head pain. This is the official journal of the American Headache Society.
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