Cinnamophilin offers prolonged neuroprotection against gray and white matter damage and improves functional and electrophysiological outcomes after transient focal cerebral ischemia

Tsung Ying Chen, Shih Huang Tai, E. Jian Lee, Chien Chih Huang, Ai Chiang Lee, Sheng Yang Huang, Tian Shung Wu

研究成果: Article同行評審

20 引文 斯高帕斯(Scopus)

摘要

OBJECTIVE: We have previously shown that cinnamophilin ([8R, 8′S]-4, 4′-dihydroxy-3, 3′-dimethoxy-7-oxo-8, 8′-neolignan) exhibited potent antioxidant, radical-scavenging, and anti-inflammatory actions and reduced acute ischemic brain damage, even when it was given up to 6 hrs postinsult. Here, we characterized the long-lasting neuroprotection of cinnamophilin against gray and white matter damage and its beneficial effects on electrophysiological and functional outcomes in a model of stroke. DESIGN: Prospective laboratory animal study. SETTING: Research laboratory in a university teaching hospital. SUBJECTS: Adult male Sprague-Dawley rats (240-290 g). INTERVENTIONS: Under controlled conditions of normoxia, normocarbia, and normothermia, spontaneously breathing, halothane-anesthetized (1.0-1.5%) rats were subjected to transient middle cerebral artery occlusion for 90 mins. Cinnamophilin (80 mg/kg) or vehicle was given intravenously at reperfusion onset. MEASUREMENTS AND MAIN RESULTS: Physiological parameters, including arterial blood gases and cortical blood perfusion, somatosensory-evoked potentials, and neurobehavioral outcomes, were serially examined. Animals were euthanized at 7 days or 21 days postinsult. Gray matter and white matter (axonal and myelin) damage were then evaluated by quantitative histopathology and immunohistochemistry against phosphorylated component-H neurofilaments and myelin basic protein, respectively. After the follow-up period of 7 and 21 days, our results showed that cinnamophilin significantly decreased gray matter damage by 31.6% and 34.9% (p <.05, respectively) without notable adverse effects. Additionally, cinnamophilin effectively reduced axonal and myelin damage by 46.3-68.6% (p <.05) and 25.2-28.1% (p <.05), respectively. Furthermore, cinnamophilin not only improved the ipsilateral field potentials (p <.05, respectively), but also reduced the severity of contralateral electrophysiological diaschisis (p <.05). Consequently, cinnamophilin improved sensorimotor outcomes up to 21 days postinsult (p <.05, respectively). CONCLUSIONS: Administration with cinnamophilin provides long-lasting neuroprotection against gray and white matter damage and improves functional and electrophysiological outcomes after ischemic stroke. The results suggest a need for further studies to characterize the potential of cinnamophilin in the field of ischemic stroke.

原文English
頁(從 - 到)1130-1137
頁數8
期刊Critical care medicine
39
發行號5
DOIs
出版狀態Published - 2011 五月

All Science Journal Classification (ASJC) codes

  • 重症監護和重症監護醫學

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