Neuroinflammation

The goal of this observational study is to study whether major surgery is linked to changes in the brain that are typical of Alzheimer's disease. The study is a prospective observational study that will be carried out in Uppsala University Hospital. Adults aged 55-75 years who are healthy otherwise (ASA1) having a hip or knee replacement under spinal anesthesia, and a comparison group of people of the same age and sex with hip or knee arthrosis who are not having surgery will be included. The main questions it aims to answer are: * Does the amount of the protein tau in the brain increase in the two years after surgery? * Are changes in tau linked to inflammation in the blood and spinal fluid, and to changes in memory and thinking? Participants will: * Have brain scans (PET and MRI) before surgery and 12 and 24 months later * Give small samples of spinal fluid and blood * Complete memory and thinking tests at the same time points Researchers will compare the surgery group with the non-surgery group to see whether surgery is associated with more tau in the brain and with changes in memory and thinking.

Heart failure reduces the amount of blood the heart pumps, which can lead to memory and thinking problems in many patients. One possible reason is that heart failure triggers brain inflammation, a process in which certain brain immune cells (called microglia) become overactive. A heart failure medication called sacubitril-valsartan has been shown to reduce the risk of developing dementia, but it is not known whether this is because it reduces brain inflammation. This study uses a new experimental brain scan drug called \[11C\]PS13 (PS13) to measure brain inflammation directly and non-invasively, using a technique called positron emission tomography (PET). PS13 sticks to a molecule called COX-1, which is found mainly in brain immune cells (microglia). By measuring how much PS13 accumulates in the brain, researchers can estimate how much brain inflammation is present. In this pilot study, 18 patients with heart failure and mild memory or thinking problems who are being started on sacubitril-valsartan by their cardiologist (as standard clinical care) will undergo two brain PET scans: one before starting sacubitril-valsartan, and one approximately 12 weeks after. The study will also assess memory, thinking, daily function, mood, and social well-being using standard questionnaires. The study will test whether sacubitril-valsartan is associated with measurable changes in brain inflammation, and whether this type of imaging is feasible in heart failure patients. The study is funded by the American Heart Association and the National Institute on Aging, and an independent Data and Safety Monitoring Board oversees participant safety. The results will be used to design a larger study.

To evaluate the potential usefulness of 18F-DPA714/FDPA positron emission tomography/computed tomography (PET/CT) for the diagnosis of primary and metastatic lesions in various TSPO-related disease patients.

This clinical trial will determine whether taking ascorbic acid (vitamin C), α-tocopherol (vitamin E), or both together can lower markers of brain inflammation and change the expression of neuropeptides in Mexican adults with obesity. Main Questions The study aims to answer: 1. Does vitamin C, vitamin E, or both reduce neuroinflammation? 2. Do these supplements change the expression of neuropeptides linked to obesity? Comparison Groups Researchers will compare the effects of vitamin C alone, vitamin E alone, and the combination of both to see if they improve brain health in people with obesity. What Participants Will Do Participants will: 1. Take vitamin C, vitamin E, or both daily, depending on their assigned group 2. Attend clinic visits once every 2 weeks for and tests for checkups and tests for record and report supplement intake so that researchers can monitor and evaluate treatment adherence 3. Provide samples and health information to measure inflammation and neuropeptides , at the beginning of the intervention and at 12 weeks, when the intervention ends.

This study is a Phase II, randomized, quadruple-blinded, placebo-controlled clinical trial designed to test whether vitamin D₃ supplementation can improve recovery after mild-to-moderate traumatic brain injury (TBI) in adults. Traumatic brain injury often leads to inflammation and poor neurological outcomes, and many patients are vitamin D-deficient. Vitamin D₃ is a safe, widely available supplement that may reduce inflammation and support brain recovery. A total of 240 adults (18-65 years) with mild-to-moderate TBI will be enrolled at Lagos State University Teaching Hospital, Nigeria. Participants will be assigned to one of four groups: Group A (Deficient + High-Dose D₃): 40,000 IU loading dose, then 4,000 IU daily for 3 weeks Group B (Deficient + Standard-Dose D₃): 2,000 IU daily for 3 weeks Group C (Sufficient + Standard-Dose D₃): 2,000 IU daily for 3 weeks Group D (Sufficient + Placebo): placebo daily for 3 weeks All groups will be followed for 24 weeks. Blood tests at baseline, week 1, week 2, and week 4 will measure inflammation. Neurological recovery will be assessed at weeks 4, 12, and 24 using the Glasgow Outcome Scale-Extended (GOS-E) and Modified Rankin Scale (mRS). The main outcomes are changes in inflammatory markers. Secondary outcomes include mortality, functional recovery, hospital stay, safety, and cost-effectiveness. The results may identify a low-cost, scalable treatment to improve outcomes after TBI, especially in low-resource settings.

Tinnitus can have different causes. From a peripheral point of view, the sensation of hearing a not present sound can be indicative of damage in the cells of the cochlea. Damage at this level can arise from traumatic, vascular, toxic origins or be caused by systemic pathologies. However, all the previous causes have a common denominator, the presence of reactive oxygen species (ROS), in the cochlea which determines the damage and the consequent death of the hair cells into the ear. The sound (tinnitus) that the patient perceives is generated by the spontaneous movement of the cilia of the hair cells; this phenomenon arises when these cells begin to be damaged. Tinnitus can be also caused by a retrocochlear disorder such as damage of the auditory nerve (inflammatory and tumor cause). In case of an inflammatory origin, the factors released during inflammation can locally damage the nerves and spread into the cochlea destroying the hair cells. Tinnitus can also originate from damage in the central auditory pathway. In this case, the problem persistent. It is important to keep in mind that although initially the tinnitus may originate from a damage inside the cochlea, after 6 months of persistence chronicizes causing an activation (without stimulus) of the upper auditory areas. This zone of "hypersensitivity" is therefore responsible for chronic tinnitus. In addition to the overmentioned medical causes, tinnitus can also be sign of psychiatric/psychological disorders, in those cases in whom there is an involvement of the hypothalamus, as showed by neuropsychological studies. Tinnitus can be temporary and disappear spontaneously or, in the most of cases, be persistent and extremely annoying/stressful for the patient. At night in particular, in the absence of noise, the patient suffers more the presence of this ghost sound, which in some occasions prevents sleep. Insomnia negatively impacts on tinnitus increasing its duration and intensity, thus establishing a perpetual cycle of stress into the brain. The latter phenomenon worses and chronicizes the symptom . Stress causes inflammation with ROS increase, which can affect both the peripheral and central auditory pathways. Recently, it has been shown that tinnitus can be a symptom of neuro-inflammatory pathologies such as, for example, Multiple Sclerosis. The effects of inflammation on the hair cells are identifiable only through electrophysiological studies or from the temporal bone. Keeping on mind inflammation and neuro-inflammation and considering the exchange between cerebrospinal fluid and perilymph , we speculate that the use of a molecule capable of reducing inflammation and modulating the action of mast cells and microglia, could be an effective tool to resolve tinnitus; moreover, thanks to its powerful action at the level of neuro-inflammation, it could reduce the hyper-activity in the upper auditory tracts, thus reducing/abolishing noise. umPeaLut combines palmitoylethanolamide, which modulates the activity of mast cells, macrophages and microglia and luteolin, a bioflanoid extracted from fruits with anti-oxidant properties, able to improve microcirculation. Because the alterations of the ear microcirculation can be an additional cause of tinnitus, we believe that luteolin content can be an ulterior benefit. Although various attempts have been made to use a mono-molecule, recent studies have shown that combination of several elements could reduce tinnitus ; PeaLut, in its ultra-micronized form with high bioavailability, could be the perfect solution. This study aims at evaluating the efficacy of umPEALUT as a therapeutic treatment of tinnitus in a sample of adults.

This prospective, observational study investigates the impact of repeated general anesthesia exposure on neuroinflammatory biomarkers and neurotrophic factors. The study will enroll 160 adult patients (aged 18-65 years) scheduled for elective cholecystectomy surgery, divided into two groups: patients with no previous general anesthesia exposure (n=80) and patients with at least one or more previous general anesthesia exposures (n=80). Serum levels of Brain-Derived Neurotrophic Factor (BDNF), Interleukin-1 beta (IL-1β), and High Mobility Group Box 1 (HMGB1) will be measured using ELISA method at two time points: preoperatively (baseline) and 24 hours postoperatively. Cognitive function will also be assessed at both time points. The primary objective is to evaluate whether multiple exposures to general anesthesia lead to significant differences in serum BDNF, IL-1β, and HMGB1 levels, reflecting changes in neurotrophic balance and neuroinflammatory response. This study aims to provide insights into the potential biochemical mechanisms underlying anesthesia-related cognitive changes and contribute original clinical data to the current literature on general anesthesia safety and neurobiological effects.

This study is a part of a larger project aiming to evaluate the neurobiological mechanisms underlying the relationship between sleep and pain in people with non-specific chronic low back pain. Specifically, this study aims to evaluate the neurobiological mechanisms underlying the relationship between chronic sleep disturbances and pain sensitivity in people with non-specific chronic low back pain and chronic insomnia.