| Grant number: | 22/06496-7 |
| Support Opportunities: | Generation Project Research Grant |
| Start date: | March 01, 2023 |
| End date: | February 29, 2028 |
| Field of knowledge: | Health Sciences - Medicine - Medical Radiology |
| Principal Investigator: | André Monteiro Paschoal |
| Grantee: | André Monteiro Paschoal |
| Host Institution: | Instituto de Física Gleb Wataghin (IFGW). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil |
| Associated researchers: | Angelina Maria Martins Lino ; Brunno Machado de Campos ; Carolina de Medeiros Rimkus ; Claudia da Costa Leite ; Dagoberto Callegaro ; Ellison Fernando Cardoso ; Fernando Campos Gomes Pinto ; Khallil Taverna Chaim ; Lydiane Hirschler ; Maria Concepción García Otaduy ; Maria da Graça Morais Martin ; Matthias van Osch |
| Associated scholarship(s): | 23/16548-7 - Evaluation of cerebrospinal fluid flow and the glymphatic system in patients with epilepsy, BP.DR |
Abstract
The blood-brain and blood-cerebrospinal fluid barriers are two important membranes in the boundary of the vascular tissue, the perivascular space, and the interstitial fluids to keep the neurovascular coupling in its normal condition. These brain barriers play a key role in selecting what is allowed to flow from the vascular side to enter in the central nervous system (CNS). In a normal condition, the brain barriers allow the passage of oxygen and nutrients, avoiding toxins to enter in the CNS. However, when the selective capability of such membranes is damaged, it can allow the leakage of toxins and other kind of cells to perfuse the CNS, which is intrinsically related to the development of many pathologies of the CNS, such as Alzheimer's disease, multiple sclerosis, intracranial hydrocephalus, small vessels diseases, among others. Therefore, assessing the integrity of the brain barriers is highly relevant to the understanding of the pathophysiology of those diseases as well as its diagnostic, monitoring of treatment efficacy and the disease's progress. Besides the selective role of the brain barriers to control what kind of molecules can enter to the CNS, they are also connected to the brain clearance mechanisms. Until the beginning of the 2010 decade, there was almost a consensus about the lack of a lymphatic system-like in the brain. However, it was recently proposed the existence of a similar system in the brain, which was called the glymphatic system. But despite there is a good agreement regarding its existence nowadays, it is far from a consensus about how it works. In that sense, two main theories were proposed in the literature, the glymphatic granulation in the veins to drain the cerebrospinal fluid (CSF) and the intramural periarterial drainage within the small arteries. However, most of the measurement of the integrity of the brain barriers as well as the CSF flow within the glymphatic system are so far invasive to the patients, by requiring for example the injection of a contrast agent, the use of a radioisotope and ionizing radiation or the need for a lumbar puncture. Therefore, the aim of the present project is to propose the development and optimization of non-invasive and quantitative MRI methods to assess the integrity of the brain barriers and to measure the CSF flow within the glymphatic system and then applying these methods to evaluate patients with altered cerebral hydrodynamic or patients with demyelinating diseases to analyze how the brain barriers and the glymphatic system are associated with its pathophysiology. (AU)
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