High fructose diet-induced obesity worsens post-ischemic brain injury in the hippocampus of female rats

ABSTRACT

Objectives: Cerebral ischemia is caused by a reduction of the blood flow in a specific area in the brain, triggering cellular cascades in the tissue that result in neuronal death. This phenomenon leads to neurological decline in patients with stroke. The extent of the injury after stroke could be related to the condition of obesity. Thus, we aim to analyze the effect of obesity induced by a high fructose diet (HFD) on the brain after cerebral ischemia in rats.

Methods: We induced the obesity model in female Wistar rats with 20% fructose in water for 11 weeks. We then performed cerebral ischemia surgery (2-vessel occlusion), carried out the neurological test 6, 24 and 48 h post-ischemia and analyzed the histological markers.

Results: The HFD induced an obese phenotype without insulin resistance. The obese rats exhibited worse neurological performance at 6 h post-ischemia and showed neuronal loss and astroglial and microglial immunoreactivity changes in the caudate putamen, motor cortex, amygdala and hippocampus at 48 h post-ischemia. However, the most commonly affected area was the hippocampus, where we found an increase in interleukin 1β in the blood vessels of the dentate gyrus, a remarkable disruption of MAP-2+ dendrites, a loss of brain-derived neurotrophic factor and the presence of PHF-tau. In conclusion, a HFD induces an obese phenotype and worsens the neuronal loss, inflammation and plasticity impairment in the hippocampus after cerebral ischemia.

KEYWORDS:

• Brain ischemia
• high fructose diet
• neuronal loss: inflammation
• loss of plasticity

Acknowledgements

We thank Tania Márquez Durango for the Vivarium technical support and Claudia Guzman for the laboratory technical support. Also, we specially thank Dr Claudia Velasquez from the Nutrition group at the University of Antioquia for her valuable scientific advice. Author contributions: All authors had full access to all data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Study concept and design: C.-G.G., G.-V.J., B.N. and P.-C.P. Acquisition of data: P.-C.P. and C.-R.L. Analysis and interpretation of data: C.-G.G., G.-V.J., B.N. and P.-C.P. Drafting of the manuscript: P.-C.P., G.-V.J. and C.-G.G. Critical revision of the manuscript for important intellectual content: P.-C.P., C.-G.G. and G-V.J. and statistical analysis: P.-C.P. obtained funding: G.-V.J. and C.-G.G. Administrative, technical and material support: C.-G.G. and G.-V.J. Study supervision: C.-G.G. and G.-V.J.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This project was funded by the ‘Corporación Universitaria Remington 2017’ (Project 4000000115-17) and Cellular and Molecular Neurobiology Area of Group of Neuroscience, University of Antioquia.

Notes on contributors

P. A. Pérez-Corredor

P. A. Pérez-Corredor is a Master student pursuing Biomedical Basic Science (CCBB) In the University of Antioquia.

J. A. Gutiérrez-Vargas

J. A. Gutiérrez-Vargas is an Assistant professor in the School of Health. Corporación Universitaria Remington.

L. Ciro-Ramírez

L. Ciro-Ramírez is an Undergraduate student and Nursing Facultyin Corporación Universitaria Remington.

Norman Balcazar

Norman Balcazar is an Associate professor, Department of Physiology and Biochemistry, and a Faculty of Medicine in the University of Antioquia.

G. P. Cardona-Gómez

G. P. Cardona-Gómez is a Full professor, Senior Researcher, Faculty of Medicine in the University of Antioquia.