Long-term effects of environmental stimulation following hypoxia–ischemia on the oxidative state and BDNF levels in rat hippocampus and frontal cortex

• Published in: Brain research Vol. 1247; pp. 188 - 195
• Main Authors: Pereira, Lenir Orlandi, Nabinger, Patrícia Machado, Strapasson, Atahualpa Cauê Paim, Nardin, Patrícia, Gonçalves, Carlos Alberto Saraiva, Siqueira, Ionara Rodrigues, Netto, Carlos Alexandre
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 09-01-2009; Elsevier
• Subjects: Animals; BDNF; Biological and medical sciences; Brain - metabolism; Brain - physiopathology; Brain-Derived Neurotrophic Factor - metabolism; Cytoprotection - physiology; Disease Models, Animal; Energy Metabolism - physiology; Environment; Environmental enrichment; Free Radicals - metabolism; Frontal cortex; Frontal Lobe - metabolism; Frontal Lobe - physiopathology; Hippocampus; Hippocampus - metabolism; Hippocampus - physiopathology; Hypoxia-Ischemia, Brain - metabolism; Hypoxia-Ischemia, Brain - physiopathology; Hypoxia-Ischemia, Brain - therapy; Male; Medical sciences; Neonatal hypoxia–ischemia; Nerve Degeneration - etiology; Nerve Degeneration - physiopathology; Nerve Degeneration - therapy; Neurology; Oxidative stress; Oxidative Stress - physiology; Rats; Rats, Wistar; Sulfhydryl Compounds - metabolism; Superoxide Dismutase - metabolism; Superoxide Dismutase-1; Thiobarbituric Acid Reactive Substances - metabolism; Time; Vascular diseases and vascular malformations of the nervous system; HIEE; HI; Oxidative stress; MDA; Frontal cortex; CTEE; control maintained in standard environment group; CA1; TBA; control submitted to environmental enrichment group; Neonatal hypoxia–ischemia; sodium dodecyl sulfate; brain-derived neurotrophic factor; malondialdehyde; CTSE; DCF-DA - 2,7; EE; SDS; dichlorofluorescein diacetate; group submitted to hypoxia–ischemia and maintained in standard environment; BDNF; DCF; oxidized fluorescent derivative; thiobarbituric acid; thiobarbituric acid reactive substances; hypoxia–ischemia; SOD; TBARS; environmental enrichment; HISE; subfield 1 of Cornus Amonis of hippocampus; TCA; superoxide dismutase; group submitted to hypoxia–ischemia followed by environmental enrichment; Hippocampus; trichloroacetic acid; Environmental enrichment; Neonatal hypoxia-ischemia; Rat; Central nervous system; Environmental factor; Cardiovascular disease; Stimulation; Stimulating environment; Encephalon; Vascular disease; Ischemia; Brain derived neurotrophic factor; Cerebrovascular disease; Human; Oxygen; Nervous system diseases; Rodentia; Long term; Cerebral disorder; Vertebrata; Mammalia; Newborn; Animal; Central nervous system disease; Brain ischemia; Hypoxia
• ISSN: 0006-8993; 1872-6240
• DOI: 10.1016/j.brainres.2008.10.017

Abstract Environmental enrichment recovers memory deficits without affecting atrophy of the hippocampus adult rats submitted to neonatal hypoxia–ischemia (HI). The present study was designed to investigate whether the modulation of brain oxidative status and/or BDNF content, as assessed in adulthood, are involved with the functional neuroprotection caused by environmental enrichment in animals receiving neonatal HI. Male Wistar rats, in the 7th postnatal day, were submitted to the Levine–Rice model of neonatal hypoxia–ischemia, comprising permanent occlusion of the right common carotid artery and a 90 min period of hypoxia (8% O2 –92% N2 ). Starting 2 weeks after the HI event, animals were stimulated by the enriched environment (1 h/day for 9 weeks). Rats were sacrificed approximately 24 h after the end of enrichment period and some oxidative stress parameters, specifically the free radical levels, macromolecules damage and superoxide dismutase activity, in hippocampus and frontal cortex samples were determined. BDNF levels were also measured in the same encephalic structures. Indexes of macromolecules damage, TBARS levels and total cellular thiols, as well as free radical levels were unchanged in both studied structures. An increased SOD activity in the right hippocampus of HI group maintained in standard environment was found, this effect was reversed in HI enriched group. Moreover, BDNF levels were increased only in the hippocampus of non-stimulated HI group. These results suggest that the environmental enrichment protocol bearing cognitive protection is not associated to increases in BDNF expression nor SOD activity in hippocampus of the rats, as assessed in adulthood, submitted to neonatal hypoxia–ischemia.