AUTHOR=Huang Taida , Huang Xiaomin , Li Hui , Qi Junhua , Wang Nan , Xu Yi , Zeng Yunxin , Xiao Xuewen , Liu Ruide , Chan Yik Lung , Oliver Brian G. , Yi Chenju , Li Dan , Chen Hui 

TITLE=Maternal Cigarette Smoke Exposure Exaggerates the Behavioral Defects and Neuronal Loss Caused by Hypoxic-Ischemic Brain Injury in Female Offspring

JOURNAL=Frontiers in Cellular Neuroscience

VOLUME=Volume 16 - 2022

YEAR=2022

URL=https://www.frontiersin.org/journals/cellular-neuroscience/articles/10.3389/fncel.2022.818536

DOI=10.3389/fncel.2022.818536

ISSN=1662-5102

ABSTRACT=Objective: Hypoxic-ischemic encephalopathy affects ~6 in 1,000 neonates, leading to significant neurological sequela (e.g. cognitive deficits and cerebral palsy). Maternal smoke exposure (SE) is one of the common causes of neurological disorders; however, female offspring seems to be less affected than males in our previous study. We also showed that maternal SE exaggerated neurological disorders caused by neonatal hypoxic-ischemic brain injury in adolescent male offspring. Here, we aimed to examine whether female littermates of these males are protected from such insult.
Methods: BALB/c dams were exposed to cigarette smoke generated from 2 cigarettes twice daily for 6 weeks before mating, during gestation and lactation. To induce hypoxic-ischemic brain injury, half of the pups from each litter underwent left carotid artery occlusion, followed by exposure to 8% oxygen (92% nitrogen) at postnatal day (P) 10. Behavioral tests were performed at P40-45, and brain tissues were collected at P45.
Results: Maternal SE worsened the deficits in short-term memory and motor function in females with hypoxic-ischemic injury; however, reduced anxiety due to injury was observed in the control offspring, but not the SE offspring. Both hypoxic-ischemic injury and maternal SE caused significant loss of neuronal cells and synaptic proteins, along with increased oxidative stress and inflammatory responses. 
Conclusions: Oxidative stress and inflammatory response due to maternal SE may be the mechanism of worsened neurological outcomes by hypoxic-ischemic brain injury in females, which was similar to their male littermates shown in our previous study.