Perinatal hypoxic/ischemic brain damage in C57bl6/c induces sensorimotor deficits, anxiety-like behaviors and cognitive impairment during adulthood in a gender-selective manner

MUNTSANT, A; TORRES-VISTA, V; CHERTOFF, MARIELA; SHRIVASTAVA KALPANA; RECASENS MIREIA; LLOVERA GEMMA; ACARIN LAIA; GIMENEZ LLORT LYDIA

BARCELONA

Congreso; FENS Forum 2012; 2012

FENS

Perinatal brain injury leads to various neurological disabilities throughout life including attention and motor deficits, cognitive limitations, learning difficulties and even severe disabilities such as cerebral palsy. For various reasons, the neonatal brain damage has not been widely studied causing limited therapeutic outcomes. The aim of the current study is to characterize the behavioral profile of the C57BL6/C mice following Hypoxia/Ischemia (HI) that will be also useful to assess the behavioral outcome of  therapeutical strategies. HI brain damage was induced in mice at postnatal day 7 by permanent left carotid occlusion and exposure to hypoxia. After surgery, pups were returned to their dam for at least 1.5 hours to recover and thereafter placed for 55 minutes in a hypoxic chamber (8% O2). A group of shams were used for comparison. Animals of both genders were behaviorally assessed, in a longitudinal study at weaning and adulthood, for: 1) Sensorimotor function (reflexes, wire hang test, cylinder test); 2) Locomotor and daily life activites (open-field test, self-grooming); 3) Emotional and anxiety-like behaviors (corner and open-field tests, dark-light box test); 4) Learning and memory (T-maze test, Morris water maze). The results indicate that HI affected equilibrium and coordination during the ontogeny while during the adulthood sensorimotor deficiences were only observed at the level of reflexes. HI induced changes in self-grooming, neophobia and anxiety-like behavior that lead to reduced exploratory activity in all the tests, with males being selectively affected. Cognitive deficits were observed in both genders with reduced total learning capacities (acquisition of the task) and worse long-term learning, while short-term learning and memory was less affected. In conclusion, HI brain damage affected motor development and sensoriomotor functions, induced anxiety-like behaviors and cognitive deficits during the adulthood and in a gender-selective manner.