Related Experiment Video
Updated: Jul 4, 2025
Sub-acute Cerebral Microhemorrhages Induced by Lipopolysaccharide Injection in Rats
Published on: October 17, 2018
Effect of high-fat diet on cerebral pathological changes of cerebral small vessel disease in SHR/SP rats
Yuchi Zhang1,2, Abdullah Md Sheikh3, Shatera Tabassum3
1Department of Neurology, Faculty of Medicine, Shimane University, 89-1 Enya-Cho, Izumo, 693-8501, Japan.
Insights
A high-fat diet worsens cerebral small vessel disease (CSVD) in hypertensive rats by increasing oxidative stress and neuroinflammation, leading to white matter damage.
Area of Science:
- Neurology
- Vascular Biology
- Dietary Science
Background:
- Cerebral small vessel diseases (CSVD) involve white matter changes and microbleeds, with hypertension as a key risk factor.
- High-fat diets (HFD) can impact peripheral vascular health, but their specific effects on cerebral small vessels, especially in the context of hypertension, require further investigation.
Purpose of the Study:
- To investigate the impact of a high-fat diet (HFD) on cerebral small vessel pathology in normotensive and hypertensive rat models.
- To elucidate the underlying mechanisms, including oxidative stress, inflammation, and blood-brain barrier integrity, by which HFD affects cerebral small vessels.
Main Methods:
- Utilized MRI to assess white matter hyperintensity and performed pathological analysis of brain tissue.
- Quantified blood-brain barrier (BBB) protein levels (claudin 5, collagen IV), and measured markers of oxidative stress (Gp91-phox), hypoxia (HIF-1α), and neuroinflammation (astrocytes, microglia).
Main Results:
- HFD exacerbated white matter hyperintensity and pathological changes in hypertensive rats (SHR/SP).
- HFD increased collagen IV deposition and vessel leakage, particularly in the corpus callosum of SHR/SP rats.
- Elevated levels of oxidative stress, hypoxia-inducible factor-1α (HIF-1α), and neuroinflammatory markers were observed in HFD-fed hypertensive rats.
Conclusions:
- High-fat diet intensifies cerebral pathological alterations in hypertensive rats with CSVD.
- The exacerbation is mediated by increased oxidative stress and HIF-1α, leading to neuroinflammation, vascular remodeling, and white matter damage.
Abstract:
Cerebral small vessel diseases (CSVD) are neurological disorders associated with microvessels, manifested pathologically as white matter (WM) changes and cortical microbleeds, with hypertension as a risk factor. Additionally, a high-fat diet (HFD) can affect peripheral vessel health. Our study explored how HFD affects cerebral small vessels in normotensive WKY, hypertensive SHR, and SHR/SP rats. The MRI results revealed that HFD specifically increased WM hyperintensity in SHR/SP rats. Pathologically, it increased WM pallor and vacuolation in SHR and SHR/SP rats. Levels of blood-brain barrier (BBB) protein claudin 5 were decreased in SHR and SHR/SP compared to WKY, with HFD having minimal impact on these levels. Conversely, collagen IV levels remained consistent among the rat strains, which were increased by HFD. Consequently, HFD caused vessel leakage in all rat strains, particularly within the corpus callosum of SHR/SP rats. To understand the underlying mechanisms, we assessed the levels of hypoxia-inducible factor-1α (HIF-1α), Gp91-phox, and neuroinflammatory markers astrocytes, and microglia were increased in SHR and SHR/SP compared to WKY and were further elevated by HFD in all rat strains. Gp91-phox was also increased in SHR and SHR/SP compared to WKY, with HFD causing an increase in WKY but little effect in SHR and SHR/SP. In conclusion, our study demonstrates that HFD, in combined with hypertension, intensifies cerebral pathological alterations in CSVD rats. This exacerbation involves increased oxidative stress and HIF-1α in cerebral vessels, triggering neuroinflammation, vascular basement membrane remodeling, IgG leakage, and ultimately WM damage.
