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.

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.

• Authors: Tsung-Ying Chen, Shih-Huang Tai, E-Jian Lee, Chien-Chih Huang, Ai-Chiang Lee, Sheng-Yang Huang, Tian-Shung Wu
• Journal: Critical care medicine (Crit Care Med) Vol. 39 Issue 5 Pg. 1130-7 (May 2011) ISSN: 1530-0293 [Electronic] United States
• PMID: 21283002 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antioxidants
• Lignans
• Neuroprotective Agents
• cinnamophilin
• Guaiacol

Topics

• Animals
• Antioxidants (pharmacology)
• Behavior, Animal (drug effects)
• Body Weight
• Brain (drug effects, pathology)
• Cerebral Cortex (drug effects, pathology)
• Confidence Intervals
• Disease Models, Animal
• Electrophysiology
• Evoked Potentials, Somatosensory
• Guaiacol (analogs & derivatives, pharmacology)
• Ischemic Attack, Transient (drug therapy, pathology, prevention & control)
• Lignans (pharmacology)
• Male
• Nerve Fibers, Myelinated (drug effects, pathology)
• Nerve Fibers, Unmyelinated (drug effects, pathology)
• Neuroprotective Agents (pharmacology)
• Oxidative Stress (drug effects)
• Random Allocation
• Rats
• Rats, Sprague-Dawley
• Severity of Illness Index
• Statistics, Nonparametric
• Survival Rate