Brain Interstitial Fluid Drainage Alterations in Glioma-Bearing Rats

Abstract

Real time imaging and measurement of the drug distribution in the brain interstitial space (ISS) are able to determine the effeicency of local brain drug delivery to treatment gliomas. In the present study, we used a tracer-based magnetic resonance imaging (MRI) method to quantitatively analyze the effects of glioma growth on ISF drainage. Sprague-Dawley rats were randomly divided into six groups (n = 6). C6 glioma cells were implanted into either the caudate nucleus or thalamus of rats and then were examined 10 or 20 days after implantation. The two control groups were treated with vehicle. A tracer was injected into the caudate nucleus of control rats and rats with gliomas growing in the thalamus for 10 or 20 days. The tracer was similarly injected into the thalamus of control rats and rats implanted with gliomas in the caudate nucleus. The diffusion and clearance parameters of the tracer were calculated using tracer-based MRI techniques. We found that glioma implanted in the caudate nucleus significantly decreased the speed of the ISF flow in thalamus. With the growth of the glioma in thalamus, the drainage route of the brain ISF flow was altered in the caudate nucleus, but the speed of the flow was not significantly changed. These findings indicate that tracer-based MRI is a promising technique for optimizing the interstitial administration of therapeutics aimed at treating brain gliomas.

The Drainage of Interstitial Fluid in the Deep Brain is Controlled by the Integrity of Myelination

“…We further demonstrated an abnormal leakage of the traced ISF to the adjacent ECS division in a demyelinated rat brain (Fig.4). Indeed, a similar disturbance has been reported in an aggressive C6 glioma model [25]. Thus, we demonstrate that the brain is protected not only by the blood-brain barrier (BBB), which avoids potential exogenous damage through the vascular system, but is also protected by an internal ISF drainage barrier to avoid potentially harmful interference from other ECS divisions in the deep brain.…”

The Alteration of Brain Interstitial Fluid Drainage with Myelination Development

“…The ECS was thus compartmentalized. In our previous study, we verified that the regionalized ISF drainage is important for maintaining normal brain functions, which can be impeded with cuprizone-induced demyelination [ 5 , 6 , 9 ]. Therefore, we hypothesized that a regionalized ISF drainage provides local homeostasis of the working environment for neurons and glial cells.…”

“…Our results suggest that this regionalized ISF drainage system may be of importance for maintaining the brain’s normal function. Combined with previous research, a matured ISF drainage system can prevent transmitters’ interference from different ECS divisions and may assist the remote signal conduction of neurons in the same ECS along the ISF drainage pathway [ 5 , 8 , 9 , 29 ]. Our findings are in keeping with developing literature highlighting a previously underappreciated role of myelin in regulating the ISF drainage [ 8 ], and we show that changes in ISF drainage correlate with the developmental changes in the brain function of rats.…”

“…The whole image of the sample of a designated area can then be obtained by image reconstruction after scanning. Experimental fluorescence images were collected with the LSCM Merging function [ 6 , 9 ].…”

A Hybrid Titanium-Softmaterial, High-Strength, Transparent Cranial Window for Transcranial Injection and Neuroimaging

“…On the other hand, the technique of direct drug delivery into brain tissues has attracted much attention in recent years [ 32 , 34 , 35 , 36 , 37 , 38 , 39 ]. Han et al reported that injecting drugs into the extracellular space of brain tissues might provide an efficient path to overcome the blood-brain barrier (BBB) in the treatment of stroke [ 40 , 41 , 42 ]. Trans-cranium injection of drugs may also benefit developing novel clinic therapies for brain tumor and other brain function disorders [ 38 , 43 ].…”