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Updated: May 2, 2026
A Murine Model of Subarachnoid Hemorrhage
Published on: November 21, 2013
Dexmedetomidine Improves BBB and Neuronal Damage in Subarachnoid Hemorrhage by Repressing S100A4-Mediated Astrocytic
Jiaxiang Yin1, Qiaomin Xu1, Kuan Lu1
1Department of Anesthesiology, Lishui Hospital of Wenzhou Medical University, The First Affiliated Hospital of Lishui University, Lishui People's Hospital, Lishui, Zhejiang, China.
Objectives:
Following subarachnoid hemorrhage (SAH), long-lasting inflammation triggered by activated glial cells has adverse effects on neurological recovery. As an α2 adrenoceptor agonist commonly utilized for sedative purposes, dexmedetomidine (DEX) has demonstrated the ability to confer neuroprotective effects across diverse physiological or pathological conditions. This study was designed to determine whether DEX protects against SAH by altering astrocytic reactivity.
Methods:
Eight-week-old male C57BL/6 mice were subjected to experimental SAH. They were treated with DEX in the presence or absence of the α2 adrenoceptor antagonist atipamezole (ATI) via intraperitoneal injection. Neurological function was evaluated on the basis of a modified Garcia score and beam balance test. TUNEL staining was conducted to assess neuronal apoptosis. Western blotting was carried out to determine the expression of Bcl-2, Bax, and cleaved caspase-3 in the hippocampus and ZO-1 and occludin in the cortex, and ELISA was conducted to measure TNF-α, IL-6, IL-1β, and HMGB1 expression. The wet‒dry method was employed to measure the water content in the brain tissue. The permeability of the blood‒brain barrier (BBB) was assessed via Evans blue staining. Primary astrocytes were treated with S100A4 and/or DEX. The expression levels of GFAP, C3, GBP2, Serping 1, PTX3, S100A10, S100A4, and the NF-κB pathway were also determined.
Results:
DEX improved early neurological deficits in SAH mice, mitigated the permeability of the BBB, and reduced the brain water content. DEX attenuated neuronal apoptosis and proinflammatory cytokine (TNF-α, IL-6, IL-1β and HMGB1) expression in the cortex. However, DEX-mediated protective effects were attenuated by ATI administration. Additionally, DEX attenuated GFAP, C3, Serping1, S100A4, and NF-κB pathway activation in the brain and in S100A4-treated primary astrocytes, whereas ATI reversed the effects of DEX.
Conclusion:
DEX has neuroprotective and anti-inflammatory effects in SAH through the inhibition of S100A4-mediated astrocytic "A1" polarization via the activation of the α2A adrenoceptor.
