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Updated: Jun 30, 2026
Modeling Stroke in Mice: Focal Cortical Lesions by Photothrombosis
Published on: May 6, 2021
Intermittent hypoxia ameliorates behavioral deficits and exerts neurorestoration in a mouse photothrombotic stroke
Tao Wu1,2, Shu Feng1, Mengjie Chen1
1School of Physical Education and Sports Science, South China Normal University, Guangzhou 510006, China.
Background:
Ischemic stroke disproportionately impacts the elderly with a higher risk and poor repair. Current therapeutic options are constrained by narrow time windows, strict contraindications, and suboptimal efficacy in older patients, leaving a critical unmet clinical need. Hypoxia-based interventions exert preclinical neuroprotective effects, yet the effects and underlying mechanisms of intermittent hypoxia (IH) in elderly patients with ischemic stroke remain unclear.
Methods:
This study tested IH in 25-month-old C57BL/6J mice with photothrombotic (PT) stroke, randomizing to Control, PT, or PT+IH groups. IH post-conditioning was administered a total of 7 sessions on days 3-16. One session consists of a 10-min phase with 8% oxygen, followed by a 10-min phase with room air. Behavioral changes were measured through the maximal grip strength test, beam balance test, cylinder test, adhesive removal test, grid-walking test, and open field test. Neuropathological changes and potential molecular mechanisms were analyzed via immunofluorescence staining and western blotting.
Results:
Our findings demonstrated that IH treatment significantly reduced cortical infarct volume and ameliorated PT-induced sensorimotor deficits in aged mice. Furthermore, IH alleviated neuronal damage and apoptosis, preserved cerebrovascular morphology, and attenuated excessive astrocyte-vasculature interactions. Mechanistically, IH upregulated astrocyte-specific hypoxia-inducible factor 1α (HIF-1α), mitigated mitochondrial fragmentation, and shifted the polarization of microglia and astrocytes from pro-inflammatory (M1/A1) to anti-inflammatory (M2/A2) phenotypes. Collectively, these effects contributed to enhanced neurogenesis and angiogenesis in the peri-infarct region.
Conclusion:
In conclusion, these findings confirm IH's neurorestoration in aged stroke mice, potentially via HIF-1α-related regulation of mitochondrial function, glial polarization, and vascular integrity, supporting its translational potential.
