Central Nervous System Field Research Articles

Carrier-Mediated Delivery of Low-Molecular-Weight N-Containing Drugs across the Blood–Brain Barrier or the Blood–Retinal Barrier Using the Proton-Coupled Organic Cation Antiporter

While it is true that pharmacotherapy has achieved desired health outcomes, significant unmet medical needs persist in the field of central nervous system (CNS) drugs, particularly for neurodegenerative diseases such as Alzheimer’s disease, as well as ocular diseases such as diabetic retinopathy and age-related macular degeneration. Drugs cannot enter the brain from the bloodstream due to the presence of the blood–brain barrier (BBB). Similarly, they cannot enter the eyes from the bloodstream due to the blood–retina barrier (BRB), which is composed of the endothelium or the epithelium. Thus, innovative drug delivery systems that can overcome these barriers based on efflux transporters, hydrophobic lipid bilayer membranes, and tight junctions should be developed using patient-friendly techniques distinct from craniotomy procedures or intravitreal injections. Brain-penetrating CNS drugs and antihistamine drugs commonly share N-containing groups. These findings suggest that certain types of cation transporters are involved in their transportation across the cell membrane. Indeed, the proton-coupled organic cation (H+/OC) antiporter, whose specific characteristics remain unidentified, is responsible for transporting compounds with N-containing groups, such as clonidine and pyrilamine, at the BBB, and likely at the BRB as well. Therefore, well-designed low-molecular-weight drugs containing N-containing groups as transporter recognition units can enter the brain or the eyes through carrier-mediated transport. In this perspective review, I introduce the implementation and potential of H+/OC antiporter-mediated transport across the endothelium at the BBB or the BRB using drugs consciously designed with N-containing groups as their substrates.

Optical Coherence Tomography and Visual Evoked Potentials as Prognostic and Monitoring Tools in Progressive Multiple Sclerosis.

Understanding the mechanisms underlying progression and developing new treatments for progressive multiple sclerosis (PMS) are among the major challenges in the field of central nervous system (CNS) demyelinating diseases. Over the last 10 years, also because of some technological advances, the visual pathways have emerged as a useful platform to study the processes of demyelination/remyelination and their relationship with axonal degeneration/protection. The wider availability and technological advances in optical coherence tomography (OCT) have allowed to add information on structural neuroretinal changes, in addition to functional information provided by visual evoked potentials (VEPs). The present review will address the role of the visual pathway as a platform to assess functional and structural damage in MS, focusing in particular on the role of VEPs and OCT, alone or in combination, in the prognosis and monitoring of PMS.

Preparation and Characterization of GLUT1-mediated Novel Brain Targeting Magnetic Nanoparticles

Background: Magnetic targeting, which utilizes a magnetic field to specifically deliver therapeutic agents to the targeted regions, can greatly improve the treatment efficiency. On the other hand, glucose-modified nanoparticles have also demonstrated good brain-targeting abilities. Fusion of both might further improve the brain targeting efficiency. Objective: To prepare, characterize and evaluate glucose-modified ibuprofen-loaded brain targeting magnetic nanoparticles (MNPs-APS-Glu). Methods: The magnetic nanoparticles MNPs-APS-Glu were designed and synthesized in order to effectively deliver ibuprofen to the brain through glucose transporter 1 (GLUT1) and an external magnetic field. The nanoparticles were characterized by FTIR, SEM and magnetic properties, and the drug loading capacity, cell cytotoxicity and drug release behavior of the new magnetic nanoparticles was studied. Results: The size of MNPs-APS-Glu was about 104.9 nm, and its drug loading capacity was up to 5%. Furthermore, these brain targeting magnetic nanoparticles maintained the magnetic property with a saturation magnetization level at ca. 32 emu/g and could release ibuprofen when incubated with various buffers, mice plasma and brain homogenate. Conclusions: The results indicated that the magnetic nanoparticles had potential to be a promising tool to selectively deliver drugs to the brain. This study may be conducive to the field of Central Nervous System (CNS) drugs delivery.

The research domain criteria framework in drug discovery for neuropsychiatric diseases: focus on negative valence.

Drug discovery, particularly in the field of central nervous system, has had very limited success in the last few decades. A likely contributor is the poor translation between preclinical and clinical phases. The Research Domain Criteria of the National Institutes of Mental Health is a framework which aims to identify new ways of classifying mental illnesses that are based on observable behaviour and neurobiological measures, and to provide a guiding and evolving framework to improve the translation from preclinical to clinical research. At the core of the Research Domain Criteria approach is the assumption that the dimensional constructs described can be assessed across different units of analysis, thus enabling a more precise quantitative understanding of their neurobiological underpinnings, increasing the likelihood of identifying new and effective therapeutic approaches. In the present review, we discuss how the Research Domain Criteria can be applied to drug discovery with the domain Negative Valence, construct Potential Threat (‘Anxiety’) as an example. We will discuss the evidence supporting the utility of the Research Domain Criteria approach and evaluate how close we are to achieving a common thread of translational research from gene to self-report.

Impact of margin for target volume in low-dose involved field radiotherapy after induction chemotherapy for intracranial germinoma

Purpose We previously published a report stating that germinomas with elevated serum beta human chorionic gonadotropin (HCG-β) had a poor relapse rate, but these findings have not been supported by a multi-institutional trial. The margin for initial gross tumor volume (GTV) before surgery and chemotherapy of the same materials was investigated by retrospective review. Methods and material The 27 patients reported on in the previous paper were analyzed. The two-dimensional margin from the initial GTV to 90% of the prescribed dose of 24 Gy was 2.0 cm for a solitary lesion in the protocol. This margin was measured retrospectively without knowledge of the serum HCG-β level. The whole ventricle field was used for patients with multifocal disease and whole central nervous system field was used for disseminated disease, respectively. Results Six relapses were seen in 18 patients with solitary tumors, and were treated with the minimum margin of 1.5 cm or less to the initial GTV. Five of the 6 had initially elevated serum HCG-β at the median of 7.4 mIU/mL, ranging from 0.7–233 mIU/mL. No relapses were seen in the 9 patients who were treated with whole ventricle or whole central nervous system field. Conclusions An inadequate margin and elevated serum HCG-β were equally determined to be candidates that caused the poor local control. The whole ventricle is recommended as the smallest target volume for germinoma with or without elevated HCG-β after induction chemotherapy.

Collection and Use of Fetal Central Nervous System Tissue

A recent promising development in the field of central nervous system (CNS) tissue transplantation has suggested the use of human fetal CNS tissue from first trimester abortions for xenografting/explantation. Such experiments would certainly expand our knowledge of the normal developmental mechanisms in the human CNS, and allow studies of various indices of maturation and CNS function. However, the suggestion is looked upon with hesitance for ethical, legal and perhaps even for scientific reasons. The initial experiments have been very valuable, though, for our understanding of the structural and functional development of the human CNS, and several legal and ethical concerns have been addressed in working out the procedures for retrieving such tissue. This article tries to put our present knowledge in the right perspective of scientific achievements and potential, legal restrictions and ethical concerns.

Collection and use of aborted central nervous system material. Commendation and controversy.

A recent promising development in the field of central nervous system (CNS) transplantation has suggested the use of human fetal CNS tissue from first trimester abortions for xenografting/explantation. Such experiments would certainly expand our knowledge of the normal developmental mechanisms in human CNS, and allow studies of various indices of maturation and CNS function. However, the suggestion is looked upon with hesitance for ethical, legal and perhaps even for scientific reasons. The initial experiments have been very valuable, though, for our understanding of the structural and functional development of the human CNS, and several legal and ethical concerns have been addressed in working out the procedures for retrieving such tissue. This article tries to put our present knowledge in the right perspective of scientific achievements and potential, legal restrictions and ethical concerns.