How astrocyte networks may contribute to cerebral metabolite clearance
نویسندگان
چکیده
The brain possesses an intricate network of interconnected fluid pathways that are vital to the maintenance of its homeostasis. With diffusion being the main mode of solute transport in cerebral tissue, it is not clear how bulk flow through these pathways is involved in the removal of metabolites. In this computational study, we show that networks of astrocytes may contribute to the passage of solutes between tissue and paravascular spaces (PVS) by serving as low resistance pathways to bulk water flow. The astrocyte networks are connected through aquaporin-4 (AQP4) water channels with a parallel, extracellular route carrying metabolites. Inhibition of the intracellular route by deletion of AQP4 causes a reduction of bulk flow between tissue and PVS, leading to reduced metabolite clearance into the venous PVS or, as observed in animal studies, a reduction of tracer influx from arterial PVS into the brain tissue.
منابع مشابه
Norepinephrine Controls Astroglial Responsiveness to Local Circuit Activity
Astrocytes perform crucial supportive functions, including neurotransmitter clearance, ion buffering, and metabolite delivery. They can also influence blood flow and neuronal activity by releasing gliotransmitters in response to intracellular Ca(2+) transients. However, little is known about how astrocytes are engaged during different behaviors in vivo. Here we demonstrate that norepinephrine p...
متن کاملProbing astrocyte metabolism in vivo: proton magnetic resonance spectroscopy in the injured and aging brain
Following a brain injury, the mobilization of reactive astrocytes is part of a complex neuroinflammatory response that may have both harmful and beneficial effects. There is also evidence that astrocytes progressively accumulate in the normal aging brain, increasing in both number and size. These astrocyte changes in normal brain aging may, in the event of an injury, contribute to the exacerbat...
متن کاملCellular and Molecular Mechanisms Involved in Neuroinflammation after Acute Traumatic Spinal Cord Injury
Introduction: Spinal cord injury (SCI) following traumatic events is associated with the limited therapeutic options and sever complications, which can be partly due to inflammatory response. Therefore, this study aims to explore the role of inflammation in spinal cord injury. The findings showed that the pathological conditions of nervous system lead to activation of microglia, astrocyte, neut...
متن کاملO21: Aquaporinopathy and Cerebral Inflammation
Many mammalian AQPs, including AQP1, AQP2, AQP4, AQP5 and AQP8, function primarily as bidirectional water-selective transporters. Cells expressing AQPs on their plasma membrane have an ~5- to 50-fold higher osmotic water permeability than membranes that do not. Water transport through single-file pores poses a biophysical limitation on the efficiency with which AQPs can transport water, so that...
متن کاملAcidosis causes failure of astrocyte glutamate uptake during hypoxia.
Failure of glutamate uptake during ischemia can lead to neurotoxic accumulations of glutamate in brain extracellular space. Hypoxia and acidosis are metabolic consequences of ischemia that may individually or in combination impair glutamate uptake. We used primary rat astrocyte cultures to study the effects of acidosis, chemical hypoxia, and the combination of acidosis plus chemical hypoxia on ...
متن کامل