Ascorbate deficiency confers resistance to hippocampal neurodegeneration after asphyxial cardiac arrest in juvenile rats.

Michael S Wolf, Mioara D Manole, Lee Ann New, Yaming Chen, Elif Soysal, Patrick M Kochanek, Hülya Bayır, Robert S B Clark

Pediatric research 2022 Mar

filter terms:

Asphyxial cardiac arrest (CA) is a significant cause of death and disability in children. Using juvenile Osteogenic disorder Shionogi (ODS) rats that, like humans, do not synthesize ascorbate, we tested the effect of ascorbate deficiency on functional and histological outcome after CA. Postnatal day 16-18 milk-fed ODS and wild-type Wistar rats underwent 9-min asphyxial CA (n = 8/group) or sham surgery (n = 4/group). ODS mothers received ascorbate in drinking water to prevent scurvy. Levels of ascorbate and glutathione (GSH) were measured in plasma and hippocampus at baseline and after CA. Neurologic deficit score (NDS) was measured at 3, 24, and 48 h and hippocampal neuronal counts, neurodegeneration, and microglial activation were assessed at day 7. ODS rats showed depletion of plasma and hippocampal ascorbate, attenuated hippocampal neurodegeneration and microglial activation, and increased CA1 hippocampal neuron survival vs. Wistar rats while NDS were similar. Hippocampal GSH levels were higher in ODS vs. Wistar rats at baseline and 10 min, whereas hypoxia-inducible factor-1α levels were higher in Wistar vs. ODS rats at 24 , after CA. Ascorbate-deficient juvenile ODS rats appear resistant to neurodegeneration produced by asphyxia CA, possibly related to upregulation of the endogenous antioxidant GSH in brain. Like humans and unlike other rodents, osteogenic disorder Shionogi (ODS) rats do not synthesize ascorbate, and thus may serve as a useful model for studying the role of ascorbate in human disease. Conflicting evidence exists regarding ascorbate's protective versus detrimental effects in animal models and clinical studies. Ascorbate-deficient ODS rats are resistant to neurodegeneration after experimental cardiac arrest. © 2021. The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc.

Citation

Michael S Wolf, Mioara D Manole, Lee Ann New, Yaming Chen, Elif Soysal, Patrick M Kochanek, Hülya Bayır, Robert S B Clark. Ascorbate deficiency confers resistance to hippocampal neurodegeneration after asphyxial cardiac arrest in juvenile rats. Pediatric research. 2022 Mar;91(4):820-827