title: Window of opportunity for neuroprotection with an antioxidant, allene oxide synthase, after hypoxia-ischemia in adult male rats.
abstract: OBJECTIVE
  Oxidative stress is an early event in the cascade leading in neuronal damage after hypoxic-ischemic (HI) brain injury. In the present study, we examined the dose response and window of opportunity for neuroprotection after HI injury with Allene Oxide Synthase (AOS), an anti-oxidative enzyme of the member of cytochrome P450 family.
  
  
  METHODS
  Adult male rats received intra-cerebro-ventricular infusions of either saline (vehicle) or AOS (1 μg or 10 μg or 100 μg per rat, intracerebroventricular n = 16 all groups) either 45 min or 3 h after unilateral HI brain injury. Brains were collected 5 days later. The extent of brain damage, neuronal survival, apoptosis, and glial reactions were assessed in the striatum, hippocampus, and cortex.
  
  
  RESULTS
  Allene Oxide Synthase was associated with reduced neuronal damage scores when given 45 min, but not 3 h, after HI injury (P < 0.0001) in all brain regions. AOS treatment (10 μg) improved neuronal survival in the striatum, cortex, and hippocampus (P < 0.05, P < 0.001) and reduced the microglia reaction (P < 0.05) and numbers of caspase-3-positive cells in the hippocampus (P < 0.01).
  
  
  CONCLUSIONS
  Early blockade of oxidative stress after HI injury reduces inflammatory response, neuronal necrosis, and apoptosis. The neuroprotective effects of AOS were time of administration-dependent suggesting a relatively restricted window of opportunity for acute brain injury.
authors.affiliation: The Liggins Institute, The University of Auckland, Auckland, New Zealand.
authors.forename: Sam
authors.initials: S
authors.lastname: Mathai
authors.forename: Alistair J
authors.initials: AJ
authors.lastname: Gunn
authors.forename: Ralph Andrew
authors.initials: RA
authors.lastname: Backhaus
authors.forename: Jian
authors.initials: J
authors.lastname: Guan
mesh_terms: D000367:Age Factors; D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage*; D020925:Hypoxia-Ischemia, Brain / Q000201:enzymology* / Q000473:pathology / Q000517:prevention & control*; D057967:Infusions, Intraventricular; D019746:Intramolecular Oxidoreductases / Q000008:administration & dosage*; D008297:Male; D018696:Neuroprotective Agents / Q000008:administration & dosage*; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
chemical_list: D000975:Antioxidants; D018696:Neuroprotective Agents; D019746:Intramolecular Oxidoreductases; C021377:hydroperoxide isomerase