title: ERV enhances spatial learning and prevents the development of infarcts, accompanied by upregulated BDNF in the cortex.
abstract: OBJECTIVE
  An anti-allergic and analgesic drug, "an extract derived from the inflamed cutaneous tissue of rabbits inoculated with vaccinia virus (ERV)", has been used in medical practice in Japan and some other countries. We examined the effect of ERV, prior to induction of ischemia, on the development of cerebral infarction, on learning and memory, or on brain-derived neurotrophic factor (BDNF) levels in C57BL/6J mice.
  
  
  METHODS
  Following oral administration of ERV (the same in humans: ×1) or vehicle, daily for three consecutive weeks, temporary focal ischemia was induced by the three vessel occlusion technique. In the other group of animals, after daily ERV (Low: ×1; Med: ×3, or High dose: ×9) or vehicle administration for three weeks, we performed a quantitative assessment of spatial learning or intracerebral BDNF levels.
  
  
  RESULTS
  The volumes of infarcted lesions, brain edema and the extent of the neurological deficits were significantly reduced in the ERV-treated group. ERV treatment also enhanced spatial learning, accompanied by upregulated BDNF in the cortex.
  
  
  CONCLUSIONS
  Daily oral intake of ERV, at a clinically relevant dose, protects the brain from ischemic stroke, and also enhances the learning function in normal mice. As millions of people are currently taking the drug safely, and have been for many years in some cases, there is a need to test the inhibitory actions of the drug on progressive dementia encountered in humans with recurrent ischemic attacks or Alzheimer's disease.
authors.affiliation: Laboratory of Neurology and Neurosurgery, Research Institute, National Cerebral and Cardiovascular Center, Suita 565-8565, Osaka, Japan; Research Laboratory, Rakuwa-kai Otowa Hospital, Kyoto, Japan.
authors.forename: Yukako
authors.initials: Y
authors.lastname: Nakajo
authors.affiliation: Laboratory of Neurology and Neurosurgery, Research Institute, National Cerebral and Cardiovascular Center, Suita 565-8565, Osaka, Japan; Department of Neurosurgery, Hospital, National Cerebral and Cardiovascular Center, Suita 565-8565, Osaka, Japan; Department of Neurosurgery, China-Japan Friendship Hospital, Beijing, PR China.
authors.forename: Dong
authors.initials: D
authors.lastname: Yang
authors.affiliation: Department of Neurosurgery, Hospital, National Cerebral and Cardiovascular Center, Suita 565-8565, Osaka, Japan.
authors.forename: Jun C
authors.initials: JC
authors.lastname: Takahashi
authors.affiliation: Laboratory of Neurology and Neurosurgery, Research Institute, National Cerebral and Cardiovascular Center, Suita 565-8565, Osaka, Japan; Department of Neurosurgery, Hospital, National Cerebral and Cardiovascular Center, Suita 565-8565, Osaka, Japan; Department of Neurosurgery, Baoding No.1 Hospital, Hebei, PR China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Zhao
authors.affiliation: Department of Neurosurgery, Hospital, National Cerebral and Cardiovascular Center, Suita 565-8565, Osaka, Japan.
authors.forename: Hiroharu
authors.initials: H
authors.lastname: Kataoka
authors.affiliation: Laboratory of Neurology and Neurosurgery, Research Institute, National Cerebral and Cardiovascular Center, Suita 565-8565, Osaka, Japan; Department of Cardiovascular Science, Division of Surgical Medicine, Osaka University Graduate School of Medicine, Suita, Osaka, Japan. Electronic address: hyanamot@res.ncvc.go.jp.
authors.forename: Hiroji
authors.initials: H
authors.lastname: Yanamoto
mesh_terms: D000208:Acute Disease; D000284:Administration, Oral; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D001929:Brain Edema / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D002544:Cerebral Infarction / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D002908:Chronic Disease; D015331:Cohort Studies; D004195:Disease Models, Animal; D005106:Exploratory Behavior / Q000187:drug effects; D008297:Male; D008568:Memory; D008810:Mice, Inbred C57BL; D009043:Motor Activity / Q000187:drug effects; D018696:Neuroprotective Agents / Q000494:pharmacology*; D018697:Nootropic Agents / Q000494:pharmacology; D011134:Polysaccharides / Q000494:pharmacology*; D011897:Random Allocation; D065853:Spatial Learning / Q000187:drug effects*; D020521:Stroke / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D018696:Neuroprotective Agents; D018697:Nootropic Agents; D011134:Polysaccharides; C010491:neurotropin
keywords: BDNF; Learning and memory; Neuroprotection; Neurotrophic factor; Preclinical study