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

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

doi:10.3389/fncel.2022.818536

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

Front Cell Neurosci. 2022 Feb 18:16:818536. doi: 10.3389/fncel.2022.818536. eCollection 2022.

Authors

Taida Huang^{1

2}, Xiaomin Huang², Hui Li², Junhua Qi², Nan Wang², Yi Xu², Yunxin Zeng², Xuewen Xiao¹, Ruide Liu¹, Yik Lung Chan³, Brian G Oliver^{3

4}, Chenju Yi², Dan Li¹, Hui Chen³

Affiliations

¹ Department of Pathology, The First Affiliated Hospital of Gannan Medical University, Ganzhou, China.
² Research Center, The Seventh Affiliated Hospital of Sun Yat-sen University, Shenzhen, China.
³ School of Life Sciences, Faculty of Science, University of Technology Sydney, Sydney, NSW, Australia.
⁴ Respiratory Cellular and Molecular Biology, Woolcock Institute of Medical Research, The University of Sydney, Sydney, NSW, Australia.

Abstract

Objective: Hypoxic-ischemic encephalopathy affects ∼6 in 1,000 preterm 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 P40-44, and brain tissues were collected at P45.

Results: Maternal SE worsened the defects 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.

Conclusion: 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.

Keywords: inflammation; maternal SE; motor function; oxidative stress; short-term memory.