ABSTRACT
Type 1 diabetes is a chronic autoimmune disease that affects tens of millions of people. Diabetes mellitus is one of the strongest factors in the development of cerebrovascular diseases. In this study we used NOD.CB17 Prkdcscid mice and the pharmacological model of type 1 diabetes mellitus of different duration to study changes in the cerebral vasculature. We used two combined approaches using magnetic resonance angiography both steady and transient CFD blood flow modeling. We identified the influence of type 1 diabetes on the architectonics and hemodynamics of the large blood vessels of the brain as the disease progresses. For the first time, we detected a statistically significant change in angioarchitectonics (the angles between the vessels of the circle of Willis, cross-sections areas of vessels) and hemodynamic (maximum blood flow rate, hydraulic resistance) in animals with diabetes duration of 2 months, that is manifested by the development of asymmetry of cerebral blood flow. The result shows the negative effect of diabetes on cerebral circulation as well as the practicability of CFD modeling. This may be of extensive interest, in pharmacological and preclinical studies.
Subject(s)
Cerebral Arteries/physiology , Cerebrovascular Circulation/physiology , Diabetes Mellitus, Type 1/physiopathology , Animals , Brain/physiology , Cerebral Arteries/anatomy & histology , Diabetes Mellitus, Type 1/metabolism , Disease Models, Animal , Hemodynamics/physiology , Magnetic Resonance Angiography/methods , Male , Mice , Mice, Inbred NODABSTRACT
The glymphatic system and meningeal lymphatics have recently been characterized. Glymphatic system is a glia-dependent system of perivascular channels, and it plays an important role in the removal of interstitial metabolic waste products. The meningeal lymphatics may be a key drainage route for cerebrospinal fluid into the peripheral blood, may contribute to inflammatory reaction and central nervous system (CNS) immune surveillance. Breakdowns and dysfunction of the glymphatic system and meningeal lymphatics play a crucial role in age-related brain changes, the pathogenesis of neurovascular and neurodegenerative diseases, as well as in brain injuries and tumors. This review discusses the relationship recently characterized meningeal lymphatic vessels with the glymphatic system, which provides perfusion of the CNS with cerebrospinal and interstitial fluids. The review also presents the results of human studies concerning both the presence of meningeal lymphatics and the glymphatic system. A new understanding of how aging, medications, sleep and wake cycles, genetic predisposition, and even body posture affect the brain drainage system has not only changed the idea of brain fluid circulation but has also contributed to an understanding of the pathology and mechanisms of neurodegenerative diseases.
