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Establishment of the Model of Sensibilization by LPS Followed by Neonatal Asphyxia in Rats

Grant number: 22/04074-8
Support Opportunities:Scholarships in Brazil - Scientific Initiation
Effective date (Start): June 01, 2022
Effective date (End): December 31, 2022
Field of knowledge:Biological Sciences - Morphology - Cytology and Cell Biology
Principal Investigator:Silvia Honda Takada
Grantee:Ana Luiza Sionti Pacheco
Host Institution: Centro de Matemática, Computação e Cognição (CMCC). Universidade Federal do ABC (UFABC). Ministério da Educação (Brasil). Santo André , SP, Brazil


Prematurity is characterized by the births before the 37 week, and extreme cases of prematurity, before the 24 week, are the more fatal to neonates. Due to the immunological and pulmonary immaturity of extremely preterm neonates, inflammation and neonatal asphyxia are among the most common complications. When combined with asphyxia, neonatal inflammation potentiates brain injuries and exacerbates the damage caused by neonatal asphyxia alone, it reflects severe cases of neurodevelopmental diseases, such as autism spectrum disorder (ASD), schizophrenia, and cerebral palsy. The animal models that associate neonatal complications are called inflammatory double-hit models. In neonatal infections and asphyxia, microglial activation can occur through the binding of molecular patterns related to pathogens and lesions to the Toll-like receptor type 4 (TLR4), which in turn triggers the phosphorylation of the transcription factor NFkB, which promotes the release of cytokines and chemokines such as TNF± and IL-1² that disrupt the cellular microenvironment and can interfere with vital neurodevelopmental events. However, the pathophysiological mechanisms of the inflammatory double-hit in the developing brain are still poorly understood. In this project, we propose to establish an animal model that associates the two main neonatal complications in extremely preterm infants, inflammation and neonatal asphyxia. We will do this by injecting lipopolysaccharide (LPS) at a low dose (0.05 mg/kg) in Wistar rats neonates (P1). After 3 hours, the animals will be submitted to neonatal asphyxia through the neonatal anoxia model, hitherto not associated with neonatal inflammation. It will be analyzed the survival rate of neonates to the model, the bodyweight of neonates in the interval of stimuli, cell death associated to white and gray matter, and the modulation of inflammatory proteins in the cortex 24 hours after the stimulus. The establishment of a model faithful to clinical cases and the employment of the neonatal asphyxia model already used by the research group and not yet associated with neonatal inflammation will allow a more assertive study of the pathophysiological mechanisms not yet well established in extremely preterm infants and future therapeutic propositions. It should be noted that all equipment and resources for the execution of this project are available in the UFABC laboratories, through the support of funding agencies, including FAPESP 2020/16268-6.

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