eISSN: 1509-572x
ISSN: 1641-4640
Folia Neuropathologica
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vol. 55
Original paper

Maternal hypoxia increases hippocampal cell susceptibility to ischemia after middle cerebral artery occlusion in rat offspring

Lingxing Wang, Honghong Huang, Hongchao Cai, Yafang Chen

Folia Neuropathol 2017; 55 (4): 317-324
Online publish date: 2017/12/29
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Introduction: Maternal hypoxia induces an adverse uterine environment and may induce long-term effects in offspring. This study investigated whether maternal hypoxia increases hippocampal cell vulnerability and exacerbates neurological impairments in adult rat offspring following ischemia.

Material and methods: Pregnant Sprague-Dawley rats were randomly assigned to no maternal hypoxia or maternal hypoxia treatment groups. Adult male rat offspring were subjected to middle cerebral artery occlusion (MCAO). There were four groups: maternal + sham (MH + Sham), sham (Sham), maternal hypoxia + MCAO (MH + MCAO), and MCAO only (MCAO). Neurological deficits were evaluated. Hippocampal cell damage was observed by hematoxylin and eosin (HE) staining. Cell apoptosis in the hippocampus was detected by TdT-mediated dUTP-biotin nick-end labeling (TUNEL) staining. Caspase-3, cytochrome c, Bax, and bcl-2 expression in the hippocampus was detected by Western blot.

Results: More severe hippocampal cell damage was found in the MH + MCAO group than in the MCAO group. Additionally, neurological deficits, percentage of TUNEL positive cells, and expression of caspase-3, cytochrome c, and Bax in the hippocampus were significantly higher (p < 0.05), whereas bcl-2 expression was significantly lower (p < 0.05) in the MH + MCAO group compared to the MCAO group.

Conclusions: These findings suggest that maternal hypoxia may exacerbate hippocampal cell apoptosis in rat offspring after MCAO via alterations in the expression of cytochrome c, caspase-3, Bax, and bcl-2, which ultimately affects ischemic stroke prognosis. To our knowledge, this is the first study demonstrating that maternal hypoxia increases hippocampal cell susceptibility to ischemia in adult rat offspring.


maternal hypoxia, offspring, cerebral ischemia, hippocampus, disease susceptibility

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