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Updated: Aug 24, 2025
A Thrombotic Stroke Model Based On Transient Cerebral Hypoxia-ischemia
Published on: August 18, 2015
Effects of Hypoxia-Inducible Factor 1 (HIF-1) Signaling Pathway on Acute Ischemic Stroke
Guoliang Li1, Liang Tao2, Hui Wu3
1Department of Neurosurgery, People's Hospital of Dongxihu District, Wuhan, Hubei 430040, China.
Insights
Hypoxia-inducible factor 1 (HIF-1) is a key regulator of angiogenesis in ischemic stroke. This study shows HIF-1 activation promotes new blood vessel formation after stroke, offering therapeutic potential for brain recovery.
Area of Science:
- Neuroscience
- Molecular Biology
- Pathology
Background:
- Cerebrovascular diseases, particularly ischemic stroke, are a major health concern in China, leading to significant neurological deficits.
- Ischemia causes irreversible brain neuron damage and severe functional impairments.
Purpose of the Study:
- To investigate the role of the hypoxia-inducible factor 1 (HIF-1) pathway in regulating proangiogenesis.
- To explore new therapeutic strategies for ischemic stroke treatment by understanding HIF-1 signaling.
Main Methods:
- Establishment of a middle cerebral artery occlusion (MCAO) rat model for cerebral ischemia-reperfusion.
- Analysis of brain tissue at 6 hours, 1 day, and 3 days post-ischemia to assess molecular changes.
Main Results:
- Significant increases in VEGFR2 and HIF-1α positive cells were observed by day 3 post-ischemia.
- Increased expression of Hes1 and Factor VIII positive cells in the ischemic cortex on days 1 and 3.
- Hes1 protein expression, initially low at 6 hours, significantly increased at 1 and 3 days post-ischemia.
Conclusions:
- Ischemia and hypoxia activate the HIF-1 pathway.
- HIF-1 is identified as the primary regulatory pathway for angiogenesis following ischemic events.
- Findings suggest HIF-1 pathway modulation as a potential therapeutic target for ischemic stroke.
Background:
Epidemiological surveys show that a large number of cerebrovascular diseases occur in China every year, and among these cerebrovascular diseases, ischemic diseases are predominant. Ischemia leads to irreversible degenerative necrosis of a large number of brain neurons and severe neurological deficits.
Aims:
This study is aimed at exploring the mechanism of the major regulatory effect of hypoxia-inducible factor 1 (HIF-1) pathway on proangiogenesis and providing new ideas for the treatment of ischemic stroke.
Materials And Methods:
The rats were randomly divided into normal and ischemic control groups, and the ischemic control group was subjected to the middle cerebral artery occlusion (MCAO) cerebral ischemia model by the wire embolization method, and the rats were executed in batches at 6 h, 1 d, and 3 d after ischemia-reperfusion, and the brain tissue specimens were taken for examination to investigate the effect of hypoxia-inducible factor 1 (HIF-l) signaling pathway on acute ischemic stroke.
Results:
At 3 d, the number of VEGFR2 positive cells increased significantly, and there was a significant difference compared with the control group (P < 0.05). At 3 d, the number of HIF-1α-positive cells increased significantly, and there was a significant difference compared with the control group (P < 0.05). The number of Hes1+factor VIII positive cells in the ischemic cortex increased significantly on the 1st and 3rd day, and there was a significant difference compared with the control group (P < 0.05). The expression of Hes1 protein was significantly lower than the normal level after 6 h of ischemia, and the protein expression was significantly increased at 1 d and 3 d after ischemia (P < 0.05).
Conclusion:
By detecting the expression changes of Hesl+factor VII in the ischemic area, the results show that ischemia and hypoxia activate the HIF-1, making the HIF-l the main regulatory pathway in the process of angiogenesis after ischemia.
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