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Abstract

Background: Hypoxic-ischemic encephalopathy (HIE) is the second-leading cause of neonatal morbidity and mortality worldwide. There are sex differences in the pathophysiology of HIE, particularly in microglia, which are critical in the immune response. Prior work highlights microglial aggregation in the hippocampus of human infants as a marker for HIE, but it is unknown whether this differs by sex.

Aim: We compare the microglial response in post-mortem hippocampal tissue from male and female neonates diagnosed with HIE vs. Controls who expired from other causes.

Methods: Using a retrospective cohort design, we reviewed medical records of neonates with hippocampal tissue in the Children’s Hospital of Philadelphia (CHOP) Biobank. We prioritized cases with age controls, hippocampal tissue will undergo H&E staining and immunohistochemistry for Iba1 and CD68. Qualitative analysis will be performed by an experienced neuropathologist (AV) and quantitative analysis will be performed using ImageJ.

Results: Following review of medical records of 354 children, 269 cases were excluded (age >30 days at death). Of the remaining 85 cases, 43 had history of HIE/hypoxia, with 14 (5 male, 9 female) having classic perinatal HIE. Of the 42 Controls, we will find a match to prioritized cases based on gestational age, post-conceptional age at death, and sex. We expect microglial aggregation in HIE-diagnosed neonates compared to Controls, with greater variance in males versus females.

Conclusions: These findings could translate sex differences in microglial response observed in animals to human neonates, offering insight into the relevance of targeted microglial therapeutic strategies in preclinical development.

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Microglia in Post-Mortem Hippocampal Brain Tissue of Male and Female Neonates after HIE

Background: Hypoxic-ischemic encephalopathy (HIE) is the second-leading cause of neonatal morbidity and mortality worldwide. There are sex differences in the pathophysiology of HIE, particularly in microglia, which are critical in the immune response. Prior work highlights microglial aggregation in the hippocampus of human infants as a marker for HIE, but it is unknown whether this differs by sex.

Aim: We compare the microglial response in post-mortem hippocampal tissue from male and female neonates diagnosed with HIE vs. Controls who expired from other causes.

Methods: Using a retrospective cohort design, we reviewed medical records of neonates with hippocampal tissue in the Children’s Hospital of Philadelphia (CHOP) Biobank. We prioritized cases with age controls, hippocampal tissue will undergo H&E staining and immunohistochemistry for Iba1 and CD68. Qualitative analysis will be performed by an experienced neuropathologist (AV) and quantitative analysis will be performed using ImageJ.

Results: Following review of medical records of 354 children, 269 cases were excluded (age >30 days at death). Of the remaining 85 cases, 43 had history of HIE/hypoxia, with 14 (5 male, 9 female) having classic perinatal HIE. Of the 42 Controls, we will find a match to prioritized cases based on gestational age, post-conceptional age at death, and sex. We expect microglial aggregation in HIE-diagnosed neonates compared to Controls, with greater variance in males versus females.

Conclusions: These findings could translate sex differences in microglial response observed in animals to human neonates, offering insight into the relevance of targeted microglial therapeutic strategies in preclinical development.

 

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