title: Neuroprotection with intraventricular brain-derived neurotrophic factor in rat venous occlusion model.
abstract: BACKGROUND
  The increasing number of neurosurgical procedures for elderly patients and the development of skull base neurosurgery have increased interest in cerebral venous injury that might occur in a neurosurgical setting. Brain-derived neurotrophic factor (BDNF) may have neuroprotective effects against cerebral venous ischemia.
  
  
  OBJECTIVE
  To investigate the intraventricular effects of BDNF infusion on infarct size, suppression of apoptosis, and regional cerebral blood flow (rCBF) in cerebral venous ischemic lesions in a rat 2-vein occlusion model.
  
  
  METHODS
  Thirty-three male Wistar rats were randomly divided into BDNF-treated and vehicle control groups; each group was further randomly divided into 2-day and 7-day postocclusion groups. BDNF (2.1 μg/day) or vehicle was delivered continuously via intraventricular infusion pumps. Two adjacent contralateral cortical veins were then photochemically occluded. Two and 7 days after occlusion, we histologically measured ratios of infarct volume to contralateral hemisphere volume and counted (2-day group) terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling (TUNEL)-positive apoptotic cells in the penumbra. rCBF was measured via full-field laser perfusion imaging.
  
  
  RESULTS
  The mean infarct volume after venous occlusion was significantly smaller in BDNF-treated rats than in controls at 2 days (1.49 ± 1.44% vs 3.66 ± 1.51%; P < .05) and 7 days (0.93 ± 0.47% vs 1.69 ± 0.58%; P < .05). Two days after occlusion, there were significantly fewer TUNEL-positive apoptotic cells in the BDNF-treated rats (17.0 ± 15.1) than in the controls (39.0 ± 19.6; P < .05). There were no differences in rCBF.
  
  
  CONCLUSIONS
  After 2-vein occlusion, continuous intraventricular administration of BDNF protected the cerebral cortex against apoptosis and reduced infarct size without affecting rCBF.
authors.affiliation: Department of Neurosurgery, Nara Medical University School of Medicine, Nara, Japan. yasu-77@qj8.so-net.ne.jp
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Takeshima
authors.forename: Mitsutoshi
authors.initials: M
authors.lastname: Nakamura
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Miyake
authors.forename: Ryo
authors.initials: R
authors.lastname: Tamaki
authors.forename: Toshitaka
authors.initials: T
authors.lastname: Inui
authors.forename: Kaoru
authors.initials: K
authors.lastname: Horiuchi
authors.forename: Daisuke
authors.initials: D
authors.lastname: Wajima
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Nakase
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D020520:Brain Infarction / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control; D002545:Brain Ischemia / Q000473:pathology* / Q000503:physiopathology / Q000517:prevention & control*; D019208:Brain-Derived Neurotrophic Factor / Q000008:administration & dosage*; D002560:Cerebrovascular Circulation / Q000502:physiology; D004195:Disease Models, Animal; D007276:Injections, Intraventricular; D008297:Male; D018696:Neuroprotective Agents / Q000008:administration & dosage*; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D018696:Neuroprotective Agents