High-Fat Diet-Induced Blood–Brain Barrier Dysfunction: Impact on Allodynia and Motor in Rats

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The associations among increased pain sensitivity, obesity, and systemic inflammation have not been described as a direct link between BBB dysfunctions. To analyze the metabolic, behavioral, and inflammatory effects of a HFD and ultrastructural modifications in brain regions, we used an experimental model. Adult male Wistar rats were randomly assigned to one of two conditions, an ad libitum control group, or a high-fat-diet (60%) group (HFD-fed), for eight weeks. At the end of the protocol, glucose, and insulin tolerance tests were performed. Additionally, we analyzed the response to a normally innocuous mechanical stimulus and changes in motor coordination. At the end of the protocol, HFD-fed individuals presented increased HOMA-IR and metabolic syndrome (MetS) prevalence. HFD-fed rats also developed an increased nociceptive response to mechanical stimuli and neurological injury, resulting in impaired motor function. Hypothalamus and cerebellum neurons from HFD-fed presented with nuclear swelling, an absence of nucleoli, and karyolysis. These results reveal that HFD consumption affecting vital brain structures such as the cerebellum, hippocampus, and hypothalamus. This, in turn, causes neuronal damage, impairs cellular communication, and alters motricity and pain sensitivity. Understanding the link between BBB impairment and sensory and motor changes could lead to targeted therapeutic strategies.

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