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Effect of Dexmedetomidine on Cerebral Vasospasm and Associated Biomarkers in a Rat Subarachnoid Hemorrhage Model

Song, Young, MD, PhD*,†; Lim, Beom Jin, MD, PhD; Kim, Do-Hyeong, MD*,†; Ju, Jin Woo, MD*; Han, Dong Woo, MD, PhD*,†

Journal of Neurosurgical Anesthesiology: July 2019 - Volume 31 - Issue 3 - p 342–349
doi: 10.1097/ANA.0000000000000504
Laboratory Investigation
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Background: The α2 adrenergic agonist dexmedetomidine (DEX) has huge potential for protecting against cerebral vasospasm, a leading cause of death and disability after subarachnoid hemorrhage (SAH). Biomarker assays for SAH have recently emerged as tools for predicting vasospasm and outcomes. We investigated the effects of DEX on vasospasm and assessed relevant biomarkers in a rat SAH model.

Methods: Male Wistar rats were randomly assigned to sham (n=10), vehicle (n=10), SAH (n=10), or SAH+ DEX (n=10) groups. The SAH and SAH+DEX groups received 0.3 mL injections of autologous blood into the cisterna magna, followed by intraperitoneal injections of normal saline or 10 μg/kg DEX. Forty-eight hours later, neurological deficits as well as the basilar artery (BA) wall thickness and cross-sectional area were measured. Cerebrospinal fluid (CSF) and blood samples were obtained to assess concentrations of interleukin (IL)-6, C-reactive protein (CRP), endothelin-1, and S100-β using enzyme-linked immunosorbent assays.

Results: The SAH and SAH+DEX groups exhibited deteriorated neurological function as well as structural and morphological BA vasospasm. The SAH+DEX group showed an improved neurological function score (ie, a 52% decrease), a 10% reduction in wall thickness, and a BA cross-sectional area enlarged by 157%. Compared with the sham group, CSF levels of IL-6 and CRP in the SAH and SAH+DEX groups, as well as serum IL-6 and CRP levels in the SAH group, were significantly elevated. The SAH+DEX group showed significantly lower CSF IL-6 levels than the SAH group. Serum and CSF levels of endothelin-1 and S100-β were similar across all groups.

Conclusions: DEX administration reduced the severity of cerebral vasospasm and improved neurological function in SAH rats; this may be closely linked to reduced CSF IL-6 levels.

Departments of *Anesthesiology and Pain Medicine

Pathology

Anesthesia and Pain Research Institute, Yonsei University College of Medicine, Seoul, Republic of Korea

This study was supported by special research grant funded by the Korean Society of Neuroscience in Anesthesiology and Critical Care (KSNACC-2016) for Young Song. The remaining authors have no conflicts of interest to disclose.

Address correspondence to: Dong Woo Han, MD, PhD. E-mail: hanesth@yuhs.ac.

Received November 22, 2017

Accepted March 27, 2018

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