Hypoxia-induced cerebral angiogenesis in mouse cortex with two-photon microscopy

Area of Science:

• Neuroscience
• Physiology
• Vascular Biology

Background:

• Hypoxia, a condition of low oxygen, can trigger adaptive responses in the brain, including the formation of new blood vessels (angiogenesis).
• Understanding the dynamics of cerebral angiogenesis is crucial for developing therapies for conditions involving impaired blood flow.

Purpose of the Study:

• To characterize the spatiotemporal dynamics of cortical microvascular restructuring induced by continuous hypoxia in vivo.
• To investigate the impact of hypoxia on blood-brain barrier integrity.

Main Methods:

• Utilized in vivo two-photon microscopy to image cortical microvasculature in mice over 2-4 weeks of hypoxic exposure (8-9% oxygen).
• Performed longitudinal imaging at identical locations before and weekly during hypoxia.
• Assessed blood-brain barrier integrity using sulforhodamine 101 leakage.

Main Results:

• Observed sprouting of new capillaries from existing ones 1-2 weeks after hypoxia onset.
• Quantified an average emergence rate of 15 new vessels per mm³.
• Found the highest rate of new vessel emergence at cortical depths of 100-200 μm, indicating layer-specific responses.
• Detected no significant leakage of fluorescent dye, confirming blood-brain barrier maintenance.

Conclusions:

• Continuous hypoxia induces cortical angiogenesis in a layer-dependent manner.
• The blood-brain barrier integrity is maintained during hypoxia-induced angiogenesis.
• Further research is needed to clarify the roles of perivascular cells in this process.