Early changes to the extracellular space in the hippocampus under simulated microgravity conditions.

The smooth transportation of substances through the brain extracellular space (ECS) is crucial to maintaining brain function; however, the way this occurs under simulated microgravity remains unclear. In this study, tracer-based magnetic resonance imaging (MRI) and DECS-mapping techniques were used to image the drainage of brain interstitial fluid (ISF) from the ECS of the hippocampus in a tail-suspended hindlimb-unloading rat model at day 3 (HU-3) and 7 (HU-7). The results indicated that drainage of the ISF was accelerated in the HU-3 group but slowed markedly in the HU-7 group. The tortuosity of the ECS decreased in the HU-3 group but increased in the HU-7 group, while the volume fraction of the ECS increased in both groups. The diffusion rate within the ECS increased in the HU-3 group and decreased in the HU-7 group. The alterations to ISF drainage and diffusion in the ECS were recoverable in the HU-3 group, but neither parameter was restored in the HU-7 group. Our findings suggest that early changes to the hippocampal ECS and ISF drainage under simulated microgravity can be detected by tracer-based MRI, providing a new perspective for studying microgravity-induced nano-scale structure abnormities and developing neuroprotective approaches involving the brain ECS.

Exploring the interstitial system in the brain: the last mile of drug delivery.

Brain interstitial system (ISS) is a nanoscale network of continuously connected tubes and sheets surrounding each neural cell in the central nervous system. ISS usually accounts for ∼20% of the brain volume, far more than the cerebral blood vessels, which account for 3%. The neuronal function, signaling pathways, and drug delivery are all closely related to the microenvironment provided by ISS. The objective of this paper is to give the readers a clear outline of detection, anatomy, function, and applications of ISS. This review describes the techniques propelling the exploration for ISS in chronological order, physiological function and pathological dysfunction of ISS, and strategies for drug delivery based on ISS. Biophysical features are the focus of ISS research, in which the diffusion characteristics have dominated. The various techniques that explore ISS take advantage of this feature. ISS provides an essential microenvironment for the health of cells and brain homeostasis, which plays an important functional role in brain health and disease. Direct intracranial administration allows the diffusion of drugs directly through ISS to successfully bypass the blood-brain barrier that prevents most drugs from reaching the brain. With the deepening of understanding of the brain ISS, the new research model that takes into account brain cells, cerebral vessels, and ISS will provide a new perspective and direction for understanding, utilizing, and protecting the brain.

The brain interstitial system: Anatomy, modeling, in vivo measurement, and applications.

Although neurons attract the most attention in neurobiology, our current knowledge of neural circuit can only partially explain the neurological and psychiatric conditions of the brain. Thus, it is also important to consider the influence of brain interstitial system (ISS), which refers to the space among neural cells and capillaries. The ISS is the major compartment of the brain microenvironment that provides the immediate accommodation space for neural cells, and it occupies 15% to 20% of the total brain volume. The brain ISS is a dynamic and complex space connecting the vascular system and neural networks and it plays crucial roles in substance transport and signal transmission among neurons. Investigation of the brain ISS can provide new perspectives for understanding brain architecture and function and for exploring new strategies to treat brain disorders. This review discussed the anatomy of the brain ISS under both physiological and pathological conditions, biophysical modeling of the brain ISS and in vivo measurement and imaging techniques, including recent findings on brain ISS divisions. Moreover, the implications of ISS knowledge for basic neuroscience and clinical applications are addressed.