The inflammation of the hypothalamus is at the origin of a disruption of appetite in various pathologies. However, the administration of anti-inflammatory agents in this area of the brain is complex due to the impassability of the blood-brain barrier. Researchers from the State University of Oregon discovered a means of crossing this barrier. Potential for a whole series of conditions, including Alzheimer's disease, multiple sclerosis, Parkinson's disease and cancer cachexia.
The hypothalamus is a part of the brain below the thalamus, just above the brainstem. One of its main functions is to connect the nervous system and the endocrine system through the pituitary gland. He is therefore responsible for several metabolic processes and other activities of the autonomic nervous system. His role? Maintain the internal balance of the body. Thus, it regulates body temperature, manages sleep cycles and hormone production, then controls hunger.
Given the functions he assumes, an attack on the hypothalamus may have heavy consequences. We know for example that the inflammation of this part of the brain plays an essential role in cancer cachexia. It is a metabolism disorder caused by cancer, which causes patients to loss significantly. This syndrome is a frequent complication of cancer diseases: it affects up to 80% of patients with advanced cancer. It can also be fatal: 30% of patients die.
A protective barrier difficult to cross
Cachexia is a complication of cancer, but also other chronic diseases such as renal failure, cystic fibrosis, Crohn's disease, rheumatoid arthritis and HIV. “” As cachexy is progressing, it has a significant impact on quality of life, tolerance for treatment and chances of survival “Explains Professor Oleh Taratula, co-author of the study presenting the new mode of delivery of drugs.
Administering anti-inflammatory agents to the hypothalamus could potentially help to alleviate this disruption of appetite and metabolism. For this, they would have to manage to cross the blood-brain barrier (BHE), which isolates the brain of the rest of the organism. It consists of very tight cells, which line the blood vessels of the brain and control substances that can pass from blood to the brain.
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It lets essential nutrients (oxygen, glucose) pass, but blocks harmful substances (toxins and pathogens). The brain is thus protected from infections. Unfortunately, this protective shield can also prevent the passage of therapeutic agents.
And the problem does not stop there! “” Even if we manage to cross the BHE to the hypothalamus, another obstacle consists in reaching the target within the hypothalamus, namely the activated microglial cells which act as key mediators of inflammation “Explains Taratula.
Target microglia to alleviate inflammation
Microglia cells are resident macrophages of the central nervous system. They thus constitute its first line of defense against pathogens. As part of their immune response, they secrete cytokines and other small proteins, as well as reactive oxygen species, which contribute to orient the immune response.
However, a prolonged glial response can have harmful consequences. This chronic inflammation is indeed accompanied by a high production of pro-inflammatory cytokines. These cross the BHE and induce neuroinflammation within the hypothalamus. Microglia is believed to play a role in several neurodegenerative diseases (Alzheimer's and Parkinson diseases, multiple sclerosis) and other pathologies (heart disease, glaucoma, etc.). It is therefore she that treatments should target directly.
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To reach it, and thus treat hypothalamic inflammation, Oleh Taratula and its colleagues have designed polymer nanoparticles with double peptide, capable of both penetrating the BHE and targeting microglia. Once in microglia, the release of the drug is triggered by high levels of intracellular glutathione.
The team tested these nanoparticles on murine models of acute neuroinflammation (induced by lipopolysaccharides) and chronic (cancer cachexia of the pancreas). Their results have just appeared in the review Advanced Healthcare Materials.
Loading the Irak4 inhibitor in polymer nanotransporters composed of Peptide-PEG (5K) -PCL (10K) and Methoxy-PEG (5K) -SS-PCL (10K). Credits: Goo et al., Advanced Healthcare Materials (2025)
Nanotransporters were loaded with Iraq4 inhibitors – a key protein associated with inflammation. After intravenous administration, they have reached their destination well and effectively attenuated hypothalamic inflammation in the two animal models. This was reflected by substantial reductions in the expression of pro-inflammatory cytokines.
A method applicable to other diseases linked to brain inflammation
The treated animals have presented a significant increase (+94%) of their food consumption. They also maintained their body weight, unlike the group treated by saline solution. In the cancer cachexy model, treatment has largely preserved muscle mass. It has reduced muscle loss by 50% in terms of legs compared to witness mice.
B) Daily food consumption and c) body weight of witness mice and mice having received an injection of lipopolysaccharides (LPS) and treated with physiological serum, non-specific nanotransporters (NT-NT) or nanotransporters with two peptides (CGN-MG-NC). D) Relative quantification of pro-inflammatory cytokines (TNF, IL1B, LCN2) in the hypothalamus of each experimental group. Credits: Goo et al., Advanced Healthcare Materials (2025)
“” Our work represents a significant advance “Said Oleh Taratula. Indeed, these results underline the potential of these nanotransporters as a promising therapeutic strategy for pathologies characterized by a dysfunction of the hypothalamus, in particular cancer cachexia, where neuroinflammation plays a crucial role in the progression of the disease.
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Because the implications go far beyond the cancer cachexia! The brain of patients with Alzheimer's disease contains many activated microglial cells overexpressing interleukin-1 cytokines (IL-1). This overexpression of IL-1 leads to excessive phosphorylation of the Tau protein, linked to the development of the disease.
Similarly, in patients with multiple sclerosis, the destruction of myelin in the central nervous system is associated with the activation of microglial cells. Research has also shown that neurotoxic mediators released by brain microglia play a role in various viral and bacterial infections (HIV, herpes virus, pneumococcus, etc.).
This method of delivering drugs by nanotransporters could therefore be applied to several neurological or infectious diseases characterized by inflammation of the brain.
With an unwavering passion for local news, Christopher leads our editorial team with integrity and dedication. With over 20 years’ experience, he is the backbone of Wouldsayso, ensuring that we stay true to our mission to inform.
