A Strategy to Develop a Finite Element Model to Represent Backflow During Infusions Into Brain Tissue

Limited Efficacy ◽

Convection-enhanced delivery is a means to deliver therapeutic agents directly into brain tissue for the treatment of brain tumors and other disorders of the central nervous system. Unfortunately, recent clinical trials have demonstrated limited efficacy of this procedure and suggested that one of the main obstacles is poor distribution of the infused agent [1].

Revised Scaling Relationship for Backflow Distance Along an Infusion Catheter

ASME 2012 Summer Bioengineering Conference, Parts A and B ◽

10.1115/sbc2012-80175 ◽

2012 ◽

Author(s):

José Jaime García ◽

Joshua H. Smith

Keyword(s):

Central Nervous System ◽

Clinical Trials ◽

Nervous System ◽

Therapeutic Agents ◽

Limited Efficacy ◽

Scaling Relationship ◽

Primary Obstacle ◽

The Brain

Convection-enhanced delivery (CED) is a means to deliver therapeutic agents directly into brain tissue for the treatment of brain tumors and other disorders of the central nervous system, such as Parkinson’s disease. Recent clinical trials have shown limited efficacy of this procedure, with poor distribution of the infused agent being the primary obstacle [1]. One of the challenges with improving the distribution is the effect of backflow, in which the infused fluid preferentially flows along the outside of the catheter toward the surface of the brain rather than through the tissue toward the desired region for delivery.

Volume 1A: Abdominal Aortic Aneurysms; Active and Reactive Soft Matter; Atherosclerosis; BioFluid Mechanics; Education; Biotransport Phenomena; Bone, Joint and Spine Mechanics; Brain Injury; Cardiac Mechanics; Cardiovascular Devices, Fluids and Imaging; Cartilage and Disc Mechanics; Cell and Tissue Engineering; Cerebral Aneurysms; Computational Biofluid Dynamics; Device Design, Human Dynamics, and Rehabilitation; Drug Delivery and Disease Treatment; Engineered Cellular Environments ◽

Predictions of Drug Distribution During Infusions Into the Brain Using an Axisymmetric Finite Element Biphasic Model That Includes Backflow

10.1115/sbc2013-14707 ◽

2013 ◽

Author(s):

Alejandro Orozco ◽

Joshua H. Smith ◽

José Jaime García

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Drug Distribution ◽

Therapeutic Agents ◽

Positive Pressure ◽

Biphasic Model ◽

Limited Efficacy ◽

The Brain

Convection-enhanced delivery is a technique to infuse therapeutic agents into the brain under positive pressure for the treatment of disorders of the central nervous system. Recent clinical trials [1] have shown limited efficacy of this procedure, attributed to poor distribution of the infused agent that may be due to backflow, in which the infused fluid preferentially flows along the outside of the catheter toward the surface of the brain.

Convection-enhanced delivery to the central nervous system

Journal of Neurosurgery ◽

10.3171/2014.10.jns14229 ◽

2015 ◽

Vol 122 (3) ◽

pp. 697-706 ◽

Cited By ~ 85

Author(s):

Russell R. Lonser ◽

Malisa Sarntinoranont ◽

Paul F. Morrison ◽

Edward H. Oldfield

Keyword(s):

Drug Delivery ◽

Central Nervous System ◽

Clinical Trials ◽

Nervous System ◽

Convective Flow ◽

Clinical Applications ◽

Systemic Delivery ◽

Real Time Tracking

Convection-enhanced delivery (CED) is a bulk flow–driven process. Its properties permit direct, homogeneous, targeted perfusion of CNS regions with putative therapeutics while bypassing the blood-brain barrier. Development of surrogate imaging tracers that are co-infused during drug delivery now permit accurate, noninvasive real-time tracking of convective infusate flow in nervous system tissues. The potential advantages of CED in the CNS over other currently available drug delivery techniques, including systemic delivery, intrathecal and/or intraventricular distribution, and polymer implantation, have led to its application in research studies and clinical trials. The authors review the biophysical principles of convective flow and the technology, properties, and clinical applications of convective delivery in the CNS.

Numerical Simulation of Stress States in White Matter via a Continuum Model of 3D Axons Tethered to Glia

Volume 5: Biomedical and Biotechnology ◽

10.1115/imece2020-24667 ◽

2020 ◽

Author(s):

Parameshwaran Pasupathy ◽

Robert De Simone ◽

Assimina A. Pelegri

Keyword(s):

Central Nervous System ◽

Finite Element ◽

Nervous System ◽

White Matter ◽

Glial Cells ◽

Material Model ◽

Element Model ◽

Outer Diameter ◽

Bending Stresses ◽

Abstract A new finite element approach is proposed to study the propagation of stress in axons in the central nervous system (CNS) white matter. The axons are embedded in an extra cellular matrix (ECM) and are subjected to tensile loads under purely non-affine kinematic boundary conditions. The axons and the ECM are described by the Ogden hyperelastic material model. The effect of tethering of the axons by oligodendrocytes is investigated using the finite element model. Glial cells are often thought of as the “glue” that hold the axons together. More specifically, oligodendrocytes bond multiple axons to each other and create a myelin sheath that insulates and supports axons in the brainstem. The glial cells create a scaffold that supports the axons and can potentially bind 80 axons to a single oligodendrocyte. In this study, the microstructure of the oligodendrocyte connections to axons is modeled using a spring-dashpot approximation. The model allows for the oligodendrocytes to wrap around the outer diameter of the axons at various locations, parameterizing the number of connections, distance between connection points, and the stiffness of the connection hubs. The parameterization followed the distribution of axon-oligodendrocyte connections provided by literature data in which the values were acquired through microtome of CNS white matter. We develop two models: 1) multiple oligodendrocytes arbitrarily tethered to the nearest axons, and 2) a single oligodendrocyte tethered to all the axons at various locations. The results depict stiffening of the axons, which indicates that the oligodendrocytes do aid in the redistribution of stress. We also observe the appearance of bending stresses at inflections points along the tortuous path of the axons when subjected to tensile loading. The bending stresses appear to exhibit a cyclic variation along the length of the undulated axons. This makes the axons more susceptible to damage accumulation and fatigue. Finally, the effect of multiple axon-myelin connections in the central nervous system and the effect of the distribution of these connections in the brain tissue is further investigated at present.

Delivery of Therapeutic Agents to the Central Nervous System and the Promise of Extracellular Vesicles

Pharmaceutics ◽

10.3390/pharmaceutics13040492 ◽

2021 ◽

Vol 13 (4) ◽

pp. 492

Author(s):

Charlotte A. René ◽

Robin J. Parks

Keyword(s):

Central Nervous System ◽

Endothelial Cells ◽

Nervous System ◽

Blood Brain Barrier ◽

Extracellular Vesicles ◽

Therapeutic Agents ◽

Target Cells ◽

Significant Barrier ◽

Delivery Vehicles

The central nervous system (CNS) is surrounded by the blood–brain barrier (BBB), a semipermeable border of endothelial cells that prevents pathogens, solutes and most molecules from non-selectively crossing into the CNS. Thus, the BBB acts to protect the CNS from potentially deleterious insults. Unfortunately, the BBB also frequently presents a significant barrier to therapies, impeding passage of drugs and biologicals to target cells within the CNS. This review provides an overview of different approaches to deliver therapeutics across the BBB, with an emphasis in extracellular vesicles as delivery vehicles to the CNS.

Effects of an injectable functionalized self-assembling nanopeptide hydrogel on angiogenesis and neurogenesis for regeneration of the central nervous system

Nanoscale ◽

10.1039/c7nr06528k ◽

2017 ◽

Vol 9 (42) ◽

pp. 16281-16292 ◽

Cited By ~ 21

Author(s):

Tzu-Wei Wang ◽

Kai-Chieh Chang ◽

Liang-Hsin Chen ◽

Shih-Yung Liao ◽

Chia-Wei Yeh ◽

...

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Brain Tissue ◽

Tissue Regeneration ◽

Self Assembling ◽

System P ◽

Injured Brain ◽

Functionalised self-assembling nanopeptide hydrogel mediates angiogenesis and neurogenesis for injured brain tissue regeneration.

Response of rat Brain Tissue for the Extraction of125I Antipyrine after Single and Fractionated Roentgen Ray Doses a Comparison of Fractionation Models Applied to the Central Nervous System

Acta Radiologica Oncology ◽

10.3109/02841868509134415 ◽

1985 ◽

Vol 24 (5) ◽

pp. 445-450 ◽

Cited By ~ 2

Author(s):

M. A. Pitkänen ◽

J. W. Hopewell

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Rat Brain ◽

Brain Tissue ◽

Rat Brain Tissue

On serological distinction between infiltrating neoplasm (glioma) and normal brain tissue

Kazan medical journal ◽

10.17816/kazmj49808 ◽

1935 ◽

Vol 31 (1) ◽

pp. 137-137

Author(s):

Н. Reichner

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Brain Tissue ◽

Normal Brain ◽

Normal Brain Tissue ◽

Structural Differences ◽

Thanks to the work of Vitebsky and Behrens, it became known that within the neuroectoderm itself it is possible to detect immunospecific structural differences that indicate a certain organ, possibly a functionally specific imprint of individual parts of the tissue of the central nervous system.

Development of the central nervous system in guinea pig (Cavia porcellus, Rodentia, Caviidae)

Pesquisa Veterinária Brasileira ◽

10.1590/s0100-736x2016000800013 ◽

2016 ◽

Vol 36 (8) ◽

pp. 753-760 ◽

Cited By ~ 5

Author(s):

Fernanda Menezes de Oliveira e Silva ◽

Dayane Alcantara ◽

Rafael Cardoso Carvalho ◽

Phelipe Oliveira Favaron ◽

Amilton Cesar dos Santos ◽

...

Keyword(s):

Spinal Cord ◽

Central Nervous System ◽

Nervous System ◽

Guinea Pig ◽

Brain Tissue ◽

Light And Electron Microscopy ◽

Cauda Equina ◽

Neural Tube Closure ◽

Morphological Studies ◽

Abstract: This study describes the development of the central nervous system in guinea pigs from 12th day post conception (dpc) until birth. Totally, 41 embryos and fetuses were analyzed macroscopically and by means of light and electron microscopy. The neural tube closure was observed at day 14 and the development of the spinal cord and differentiation of the primitive central nervous system vesicles was on 20th dpc. Histologically, undifferentiated brain tissue was observed as a mass of mesenchymal tissue between 18th and 20th dpc, and at 25th dpc the tissue within the medullary canal had higher density. On day 30 the brain tissue was differentiated on day 30 and the spinal cord filling throughout the spinal canal, period from which it was possible to observe cerebral and cerebellar stratums. At day 45 intumescences were visualized and cerebral hemispheres were divided, with a clear division between white and gray matter in brain and cerebellum. Median sulcus of the dorsal spinal cord and the cauda equina were only evident on day 50. There were no significant structural differences in fetuses of 50 and 60 dpc, and animals at term were all lissencephalic. In conclusion, morphological studies of the nervous system in guinea pig can provide important information for clinical studies in humans, due to its high degree of neurological maturity in relation to its short gestation period, what can provide a good tool for neurological studies.