| Description: |
There is no established treatment for the longterm eVects produced by perinatal asphyxia. Thus, we investigated the neuroprotection provided by nicotinamide against the eVects elicited by perinatal asphyxia on hippocampus and behaviour observed at 30–90 days of age. Asphyxia was induced by immersing foetuses-containing uterine horns, removed from ready-to-deliver rats into a water bath at 37°C for 20 min. Caesarean-delivered siblings were used as controls. Saline or nicotinamide (0.8 mmol/kg, i.p.) was administered to control and asphyxia-exposed animals 24, 48, and 72 h after birth. The animals were examined for morphological changes in hippocampus, focusing on delayed cell death and mossy Wbre sprouting, and behaviour, focusing on cognitive behaviour and anxiety. At the age of 30–45 days, asphyxia-exposed rats displayed (1) increased apoptosis, assessed in whole hippocampus by nuclear Hoechst staining, and (2) increased mossy Wbre sprouting, restricted to the stratum oriens of dorsal hippocampus, assessed by Timm’s staining. Rats from the same cohorts displayed (3) deWcits in non-spatial working memory, assessed by a novel object recognition task, and (4) increased anxiety, assessed by an elevated plus-maze test when examined at the age of 90 days. Nicotinamide prevented the eVects elicited by perinatal asphyxia on apoptosis, working memory, and anxiety. ; Contract Grant sponsors: FONDECYT (contract Grant numbers 1080447; 11070192) (MH-M, PM, DB); Regione Autonoma della Sardegna for ScientiWc Cooperation between Italy and Chile (Italy) (contract Grant number LR 19/96; 2003) (MM, MH-M); Atlantic Innovation Fund (Canada) (contract Grant number: 181780) (RAT); International Programme for ScientiWc cooperation CONICYT/ DAAD (number 186-06-2006) (MH-M, PJG-H); NGFN + (BMBF)-TP9-Germany (PJG-H). |