RESUMO
The continuous generation of new neurons occurs in at least two well-defined niches in the adult rodent brain. One of these areas is the subgranular zone of the dentate gyrus (DG) in the hippocampus. While the DG is associated with contextual and spatial learning and memory, hippocampal neurogenesis is necessary for pattern separation. Hippocampal neurogenesis begins with the activation of neural stem cells and culminates with the maturation and functional integration of a portion of the newly generated glutamatergic neurons into the hippocampal circuits. The neurogenic process is continuously modulated by intrinsic factors, one of which is neuroinflammation. The administration of lipopolysaccharide (LPS) has been widely used as a model of neuroinflammation and has yielded a body of evidence for unveiling the detrimental impact of inflammation upon the neurogenic process. This work aims to provide a comprehensive overview of the current knowledge on the effects of the systemic and central administration of LPS upon the different stages of neurogenesis and discuss their effects at the molecular, cellular, and behavioral levels.
Assuntos
Lipopolissacarídeos , Células-Tronco Neurais , Giro Denteado , Hipocampo , NeurogêneseRESUMO
OBJECTIVE: To determine the relationship between brain abnormalities on newborn magnetic resonance imaging (MRI) and neurodevelopmental impairment at 7 years of age in very preterm children. STUDY DESIGN: A total of 223 very preterm infants (<30 weeks of gestation or <1250 g) born at Melbourne's Royal Women's Hospital had a brain MRI scan at term equivalent age. Scans were scored using a standardized system that assessed structural abnormality of cerebral white matter, cortical gray matter, deep gray matter, and cerebellum. Children were assessed at 7 years on measures of general intelligence, motor functioning, academic achievement, and behavior. RESULTS: One hundred eighty-six very preterm children (83%) had both an MRI at term equivalent age and a 7-year follow-up assessment. Higher global brain, cerebral white matter, and deep gray matter abnormality scores were related to poorer intelligence quotient (IQ) (Ps < .01), spelling (Ps < .05), math computation (Ps < .01), and motor function (Ps < .001). Higher cerebellum abnormality scores were related to poorer IQ (P = .001), math computation (P = .018), and motor outcomes (P = .001). Perinatal, neonatal, and social confounders had little effect on the relationships between the MRI abnormality scores and outcomes. Moderate-severe global abnormality on newborn MRI was associated with a reduction in IQ (-6.9 points), math computation (-7.1 points), and motor (-1.9 points) scores independent of the other potential confounders. CONCLUSIONS: Structured evaluation of brain MRI at term equivalent is predictive of outcome at 7 years of age, independent of clinical and social factors.