title: Cinnamophilin offers prolonged neuroprotection against gray and white matter damage and improves functional and electrophysiological outcomes after transient focal cerebral ischemia.
abstract: 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.
  
  
  METHODS
  Prospective laboratory animal study.
  
  
  METHODS
  Research laboratory in a university teaching hospital.
  
  
  METHODS
  Adult male Sprague-Dawley rats (240-290 g).
  
  
  METHODS
  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.
  
  
  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.
authors.affiliation: Neurophysiology Laboratory, Neurosurgical Service, Department of Surgery, National Cheng Kung University Medical Center and Medical School, Tainan, Taiwan.
authors.forename: Tsung-Ying
authors.initials: TY
authors.lastname: Chen
authors.forename: Shih-Huang
authors.initials: SH
authors.lastname: Tai
authors.forename: E-Jian
authors.initials: EJ
authors.lastname: Lee
authors.forename: Chien-Chih
authors.initials: CC
authors.lastname: Huang
authors.forename: Ai-Chiang
authors.initials: AC
authors.lastname: Lee
authors.forename: Sheng-Yang
authors.initials: SY
authors.lastname: Huang
authors.forename: Tian-Shung
authors.initials: TS
authors.lastname: Wu
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects; D001835:Body Weight; D001921:Brain / Q000187:drug effects / Q000473:pathology; D002540:Cerebral Cortex / Q000187:drug effects* / Q000473:pathology; D016001:Confidence Intervals; D004195:Disease Models, Animal; D004594:Electrophysiology; D005073:Evoked Potentials, Somatosensory; D006139:Guaiacol / Q000031:analogs & derivatives* / Q000494:pharmacology; D002546:Ischemic Attack, Transient / Q000188:drug therapy* / Q000473:pathology / Q000517:prevention & control; D017705:Lignans / Q000494:pharmacology*; D008297:Male; D009413:Nerve Fibers, Myelinated / Q000187:drug effects* / Q000473:pathology; D036421:Nerve Fibers, Unmyelinated / Q000187:drug effects* / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012720:Severity of Illness Index; D018709:Statistics, Nonparametric; D015996:Survival Rate
chemical_list: D000975:Antioxidants; D017705:Lignans; D018696:Neuroprotective Agents; C088121:cinnamophilin; D006139:Guaiacol