RESUMO
Permanent, 3-stage, 4-vessel occlusion (4-VO) was evaluated as a practicable model of progressive, cerebral hypoperfusion in rats, resulting in quantifiable, reproducible, neuronal damage within a time interval shorter than that described in the 2-VO model. The effect of permanent and graded 4-VO on cognition was also evaluated using the newly developed, aversive radial maze. The vertebral arteries (VA) plus the common carotid arteries (CCA) or internal carotid arteries (ICA) were progressively and permanently occluded, following different experimental sequences (CCA--> VA; VA-->CCA-->CCA or VA-->ICA-->ICA) with inter-stage intervals ranging from 1 to 4 weeks. Only two of four groups subjected to 2-stage 4-VO (CCA-->VA) showed modest reduction in the number of normal-appearing CA1 pyramidal cells, despite the significant treatment effect (p < 0.001-0.01 versus sham). A high rate of mortality (63.8%) was associated with 2-stage 4-VO. More pronounced and consistent neuronal damage occurred 8 weeks after 3-stage 4-VO, following the sequence VA --> CCA --> CCA (p < 0.001). One month after this schedule, profound, persistent cognitive impairment was demonstrated in the aversive radial maze (p < 0.01-0.0001). This behavioral effect was not manifested when the ICA, rather than the CCA, were occluded, despite the presence of significant, although less severe, hippocampal lesioning. The mortality rate was significantly reduced when 3-stage 4-VO was used (p < 0.0001). These consistent, histological and behavioral effects, combined with a low mortality rate, suggest that permanent, 3-stage 4-VO may represent a reliable animal model of chronic, progressive, cerebral hypoperfusion.
Assuntos
Comportamento Animal/fisiologia , Isquemia Encefálica/patologia , Isquemia Encefálica/fisiopatologia , Circulação Cerebrovascular/fisiologia , Animais , Dano Encefálico Crônico/mortalidade , Dano Encefálico Crônico/patologia , Dano Encefálico Crônico/fisiopatologia , Isquemia Encefálica/mortalidade , Contagem de Células/métodos , Modelos Animais de Doenças , Progressão da Doença , Masculino , Aprendizagem em Labirinto/fisiologia , Mortalidade , Análise Multivariada , Neurônios/patologia , Ratos , Tempo de Reação , Fatores de TempoRESUMO
UNLABELLED: The mortality and neurodevelopmental outcome of premature infants born between 25 and 33 weeks of gestational age in Fort-de-France (Martinique, French West Indies) is reported. POPULATION: The preterm cohort included 214 infants born during the years 1992 to 1995. RESULTS: The mortality rate during the hospitalization was 20%, but was only 14% when the birth weight was more than 1,000 g. The main neonatal problems were: hyaline membrane disease (34%), bronchopulmonary dysplasia (6.5%), necrotizing enterocolitis (6%), intraventricular hemorrhage (9%) and periventricular leucomalacia (2%). Twenty infants (13.5%) showed abnormal neurodevelopmental outcome, with only three having major handicap. CONCLUSION: This study shows a notable improvement in the prognosis of premature infants in Fort-de-France. Nevertheless, a strong effort must be made in very low gestational ages and very low birth weight infants.