Preprint Review Version 1 Preserved in Portico This version is not peer-reviewed

Protoplasmic Perivascular Astrocytes Play a Crucial Role in the Development of Enlarged Perivascular Spaces in Obesity, Metabolic Syndrome, and Type 2 Diabetes Mellitus

Version 1 : Received: 29 September 2023 / Approved: 29 September 2023 / Online: 29 September 2023 (11:14:38 CEST)

A peer-reviewed article of this Preprint also exists.

Hayden, M.R. Protoplasmic Perivascular Astrocytes Play a Crucial Role in the Development of Enlarged Perivascular Spaces in Obesity, Metabolic Syndrome, and Type 2 Diabetes Mellitus. Neuroglia 2023, 4, 307-328. Hayden, M.R. Protoplasmic Perivascular Astrocytes Play a Crucial Role in the Development of Enlarged Perivascular Spaces in Obesity, Metabolic Syndrome, and Type 2 Diabetes Mellitus. Neuroglia 2023, 4, 307-328.

Abstract

Abstract: Astrocytes (ACs) are the most abundant human cell in the brain and importantly, are the master connecting and communicating cells that provide structural and functional support of brain cells at all levels of organization. Further, they are recognized to be the guardians and housekeepers of the brain. Protoplasmic perivascular astrocyte endfeet and their basal lamina form the delimiting outermost barrier (glia limitans) of the perivascular spaces in postcapillary venules and are important for the clearance of metabolic waste and comprise the glymphatic system, which is critically dependent on the proper waste removal by the pvACef polarized aquaporin 4 water channels. Also, the protoplasmic perisynaptic astrocyte endfeet (psACef) are important in cradling the neuronal synapses that serve to maintain homeostasis and serve a functional and supportive role for synaptic transmission. Enlarged perivascular spaces (EPVS) are emerging as important aberrant findings on magnetic resonance imaging (MRI) and associate with white matter hyperintensities, lacunes, aging, accepted to be biomarkers for cerebral small vessel disease, increased in obesity, metabolic syndrome, and type 2 diabetes. Knowledge is exponentially expanding regarding EPVS along with the glymphatic system, since EPVS are closely associated with impaired glymphatic function and waste removal from the brain to the cerebrospinal fluid and systemic circulation. This review intends to focus on how the pvACef play a crucial role in the development of EPVS.

Keywords

BBB; endothelial glycocalyx; enlarged perivascular spaces; metabolic syndrome; neuroinflammation; neurovascular unit; obesity; perivascular spaces; perivascular unit; type 2 diabetes mellitus

Subject

Biology and Life Sciences, Neuroscience and Neurology

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