title: Lycium barbarum extracts protect the brain from blood-brain barrier disruption and cerebral edema in experimental stroke.
abstract: OBJECTIVE
  Ischemic stroke is a destructive cerebrovascular disease and a leading cause of death. Yet, no ideal neuroprotective agents are available, leaving prevention an attractive alternative. The extracts from the fruits of Lycium barbarum (LBP), a Chinese anti-aging medicine and food supplement, showed neuroprotective function in the retina when given prophylactically. We aim to evaluate the protective effects of LBP pre-treatment in an experimental stroke model.
  
  
  METHODS
  C57BL/6N male mice were first fed with either vehicle (PBS) or LBP (1 or 10 mg/kg) daily for 7 days. Mice were then subjected to 2-hour transient middle cerebral artery occlusion (MCAO) by the intraluminal method followed by 22-hour reperfusion upon filament removal. Mice were evaluated for neurological deficits just before sacrifice. Brains were harvested for infarct size estimation, water content measurement, immunohistochemical analysis, and Western blot experiments. Evans blue (EB) extravasation was determined to assess blood-brain barrier (BBB) disruption after MCAO.
  
  
  RESULTS
  LBP pre-treatment significantly improved neurological deficits as well as decreased infarct size, hemispheric swelling, and water content. Fewer apoptotic cells were identified in LBP-treated brains by TUNEL assay. Reduced EB extravasation, fewer IgG-leaky vessels, and up-regulation of occludin expression were also observed in LBP-treated brains. Moreover, immunoreactivity for aquaporin-4 and glial fibrillary acidic protein were significantly decreased in LBP-treated brains.
  
  
  CONCLUSIONS
  Seven-day oral LBP pre-treatment effectively improved neurological deficits, decreased infarct size and cerebral edema as well as protected the brain from BBB disruption, aquaporin-4 up-regulation, and glial activation. The present study suggests that LBP may be used as a prophylactic neuroprotectant in patients at high risk for ischemic stroke.
authors.affiliation: Eye Institute, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong.
authors.forename: Di
authors.initials: D
authors.lastname: Yang
authors.forename: Suk-Yee
authors.initials: SY
authors.lastname: Li
authors.forename: Chung-Man
authors.initials: CM
authors.lastname: Yeung
authors.forename: Raymond Chuen-Chung
authors.initials: RC
authors.lastname: Chang
authors.forename: Kwok-Fai
authors.initials: KF
authors.lastname: So
authors.forename: David
authors.initials: D
authors.lastname: Wong
authors.forename: Amy C Y
authors.initials: AC
authors.lastname: Lo
mesh_terms: D000818:Animals; D051401:Aquaporin 4 / Q000378:metabolism; D001812:Blood-Brain Barrier / Q000187:drug effects*; D001929:Brain Edema / Q000209:etiology / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D004195:Disease Models, Animal; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D005904:Glial Fibrillary Acidic Protein; D020244:Infarction, Middle Cerebral Artery / Q000150:complications; D032305:Lycium; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009419:Nerve Tissue Proteins / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology; D020521:Stroke / Q000150:complications / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology
chemical_list: C496031:Aqp4 protein, mouse; D051401:Aquaporin 4; D004365:Drugs, Chinese Herbal; D005904:Glial Fibrillary Acidic Protein; D009419:Nerve Tissue Proteins; D018696:Neuroprotective Agents; D010936:Plant Extracts; C528900:glial fibrillary astrocytic protein, mouse; D020780:Matrix Metalloproteinase 9; C501830:Mmp9 protein, mouse