title: Ascorbic acid protects the newborn rat brain from hypoxic-ischemia.
abstract: Ascorbic acid (AA) is a potent antioxidant, and its neuroprotective effect has not been established yet. Using the Rice-Vannucci model, we examined the effect of AA on hypoxic-ischemic (HI) injury in the immature rat brain. Under isoflurane anesthesia, 7-day-old rat pups received 750 mg/kg of AA by intraperitoneal injection just before hypoxic exposure; 8% oxygen for 90 min. Vehicle controls received an equal volume of saline. AA decreased a macroscopic brain injury score at 48 and 168 h post-HI compared with vehicle controls (48 h post-HI, AA 1.38+/-0.45 vs. controls 2.94+/-0.24, p<0.05; 168 h post-HI, 1.13+/-0.44 vs. 2.50+/-0.25, p<0.05). AA injection significantly decreased the number of both necrotic and apoptotic cells in cortex, caudate putamen, thalamus and hippocampus, and also seemed to reduce the number of TUNEL-positive cells. Western blot analysis showed that AA significantly suppressed 150/145 kDa subunits of alpha-fodrin breakdown products (FBDP) in cortex, striatum, thalamus and hippocampus at 24 and 48 h post-HI, and also 120 kDa subunit of FBDP in all examined regions except for thalamus, which indicated that AA injection inhibited both calpain and caspase-3 activation. Western blot analysis of nitrotyrosine failed to show inhibition of free radical production by AA, however, our results show that AA inhibits both necrotic and apoptotic cell death and that AA is neuroprotective after HI in immature rat brain.
authors.affiliation: Department of Pediatrics, Akita University School of Medicine, 1-1-1 Hondo, Akita, Japan. miurash@doc.med.akita-u.ac.jp
authors.forename: Shinobu
authors.initials: S
authors.lastname: Miura
authors.forename: Wako
authors.initials: W
authors.lastname: Ishida-Nakajima
authors.forename: Akira
authors.initials: A
authors.lastname: Ishida
authors.forename: Masanari
authors.initials: M
authors.lastname: Kawamura
authors.forename: Akiko
authors.initials: A
authors.lastname: Ohmura
authors.forename: Rena
authors.initials: R
authors.lastname: Oguma
authors.forename: Yoko
authors.initials: Y
authors.lastname: Sato
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Takahashi
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D000975:Antioxidants / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D001205:Ascorbic Acid / Q000627:therapeutic use*; D015153:Blotting, Western; D001921:Brain / Q000187:drug effects* / Q000648:ultrastructure; D002545:Brain Ischemia / Q000188:drug therapy* / Q000473:pathology; D002154:Calpain / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D020287:In Situ Nick-End Labeling; D008840:Microfilament Proteins / Q000378:metabolism; D008854:Microscopy, Electron; D009336:Necrosis; D009474:Neurons / Q000187:drug effects / Q000648:ultrastructure; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D051381:Rats; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism; D013049:Spectrin
chemical_list: D000975:Antioxidants; D001205:Ascorbic Acid; D002154:Calpain; D002352:Carrier Proteins; D053148:Caspase 3; D008840:Microfilament Proteins; D018696:Neuroprotective Agents; D014443:Tyrosine; D013049:Spectrin; C002744:3-nitrotyrosine