scholarly journals Facilitating drug delivery in the central nervous system by opening the blood-cerebrospinal fluid barrier with a single low energy shockwave pulse

2022 ◽  
Vol 19 (1) ◽  
Author(s):  
Yi Kung ◽  
Kuan-Yu Chen ◽  
Wei-Hao Liao ◽  
Yi-Hua Hsu ◽  
Chueh-Hung Wu ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Spinal Cord ◽  
Central Nervous System ◽  
Cerebrospinal Fluid ◽  
Nervous System ◽  
Leptomeningeal Carcinomatosis ◽  
Low Energy ◽  
Penicillin G ◽  
The Central Nervous System ◽  
Energy Flux Density

Abstract Background The blood-cerebrospinal fluid (CSF) barrier (BCSFB) is critically important to the pathophysiology of the central nervous system (CNS). However, this barrier prevents the safe transmission of beneficial drugs from the blood to the CSF and thus the spinal cord and brain, limiting their effectiveness in treating a variety of CNS diseases. Methods This study demonstrates a method on SD rats for reversible and site-specific opening of the BCSFB via a noninvasive, low-energy focused shockwave (FSW) pulse (energy flux density 0.03 mJ/mm2) with SonoVue microbubbles (2 × 106 MBs/kg), posing a low risk of injury. Results By opening the BCSFB, the concentrations of certain CNS-impermeable indicators (70 kDa Evans blue and 500 kDa FITC-dextran) and drugs (penicillin G, doxorubicin, and bevacizumab) could be significantly elevated in the CSF around both the brain and the spinal cord. Moreover, glioblastoma model rats treated by doxorubicin with this FSW-induced BCSFB (FSW-BCSFB) opening technique also survived significantly longer than untreated controls. Conclusion This is the first study to demonstrate and validate a method for noninvasively and selectively opening the BCSFB to enhance drug delivery into CSF circulation. Potential applications may include treatments for neurodegenerative diseases, CNS infections, brain tumors, and leptomeningeal carcinomatosis.

Developmental Overview of Central Neuroanatomy

2017 ◽  
Author(s):  
Peggy Mason
Keyword(s):  
Spinal Cord ◽  
Central Nervous System ◽  
Cerebrospinal Fluid ◽  
Nervous System ◽  
Cerebral Cortex ◽  
Neural Tube ◽  
The Central Nervous System ◽  
Dorsal Telencephalon ◽  
Adult Spinal Cord ◽  
The Brain

The central nervous system develops from a proliferating tube of cells and retains a tubular organization in the adult spinal cord and brain, including the forebrain. Failure of the neural tube to close at the front is lethal, whereas failure to close the tube at the back end produces spina bifida, a serious neural tube defect. Swellings in the neural tube develop into the hindbrain, midbrain, diencephalon, and telencephalon. The diencephalon sends an outpouching out of the cranium to form the retina, providing an accessible window onto the brain. The dorsal telencephalon forms the cerebral cortex, which in humans is enormously expanded by growth in every direction. Running through the embryonic neural tube is an internal lumen that becomes the cerebrospinal fluid–containing ventricular system. The effects of damage to the spinal cord and forebrain are compared with respect to impact on self and potential for improvement.

scholarly journals Toxicity of Shiga Toxin 1 in the Central Nervous System of Rabbits

2001 ◽  
Vol 69 (10) ◽  
pp. 6545-6548 ◽  
Author(s):  
Jun Fujii ◽  
Yoshimasa Kinoshita ◽  
Takashi Yutsudo ◽  
Hatsumi Taniguchi ◽  
Tom Obrig ◽  
...  
Keyword(s):  
Magnetic Resonance Imaging ◽  
Spinal Cord ◽  
Central Nervous System ◽  
Cerebrospinal Fluid ◽  
Nervous System ◽  
Magnetic Resonance ◽  
Shiga Toxin ◽  
Brain Lesions ◽  
Resonance Imaging ◽  
The Central Nervous System

ABSTRACT The action of Shiga toxin (Stx) on the central nervous system was examined in rabbits. Intravenous Stx1 was 44 times more lethal than Stx2 and acted more rapidly than Stx2. However, Stx1 accumulated more slowly in the cerebrospinal fluid than did Stx2. Magnetic resonance imaging demonstrated a predominance of Stx1-dependent lesions in the spinal cord. Pretreatment of the animals with anti-Stx1 antiserum intravenously completely protected against both development of brain lesions and mortality.

Neonatal Emergencies II: Myelomeningocele

2019 ◽  
Author(s):  
Iva Vassileva Vesselinova
Keyword(s):  
Spinal Cord ◽  
Central Nervous System ◽  
Cerebrospinal Fluid ◽  
Nervous System ◽  
Tethered Spinal Cord ◽  
Arnold Chiari Malformation ◽  
Key Words Myelomeningocele ◽  
Neurological Morbidity ◽  
The Central Nervous System ◽  
Ventriculo Peritoneal Shunt

Myelomeningocele is the most common and severe congenital malformation of the central nervous system, associated with substantial neurological morbidity, devastating lifelong medical disability and increased mortality. This review focuses on the perioperative anesthesia considerations of postnatal correction of myelomeningocele. This contains 3 tables, and 34 references. Key words: myelomeningocele, Arnold Chiari malformation, tethered spinal cord syndrome, hydrocephalus, cerebrospinal fluid, ventriculo-peritoneal shunt, latex hypersensitivity, morbidity, mortality.

Central nervous system

2017 ◽  
Author(s):  
Mark Harrison
Keyword(s):  
Spinal Cord ◽  
Central Nervous System ◽  
Emergency Medicine ◽  
Cerebrospinal Fluid ◽  
Nervous System ◽  
Blood Supply ◽  
Venous Drainage ◽  
Cerebral Hemispheres ◽  
System P ◽  
The Central Nervous System

This chapter describes the anatomy of the central nervous system as it applies to Emergency Medicine, and in particular the Primary FRCEM examination. The chapter outlines the key details of the structure, anatomy, and arteries of the cerebral hemispheres, blood supply and venous drainage, brainstem, cerebrospinal fluid, cerebellum, spinal cord, and core blood supply. This chapter is laid out exactly following the RCEM syllabus, to allow easy reference and consolidation of learning.

Correlation of the ratio of S-adenosyl-l-methionine to S-adenosyl-l-homocysteine in the brain and cerebrospinal fluid of the pig: implications for the determination of this methylation ratio in human brain

1992 ◽  
Vol 82 (1) ◽  
pp. 93-97 ◽  
Author(s):  
D. G. Weir ◽  
A. M. Molloy ◽  
J. N. Keating ◽  
P. B. Young ◽  
S. Kennedy ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Central Nervous System ◽  
Cerebrospinal Fluid ◽  
Nervous System ◽  
Nitrous Oxide ◽  
Vitamin B12 Deficiency ◽  
Neural Tissues ◽  
The Central Nervous System ◽  
Methylation Ratio

1. Pigs were maintained in air or in an atmosphere of nitrous oxide which dramatically changes the S-adenosyl-l-methionine to S-adenosyl-l-homocysteine ratio in neural tissues. Samples of cerebrospinal fluid, cortex, cerebellum and spinal cord were then extracted and analysed for S-adenosyl-l-methionine and S-adenosyl-l-homocysteine. Regression analyses were carried out on values obtained in cerebrospinal fluid and in neural tissues. 2. Highly significant correlations were obtained between levels of S-adenosyl-l-homocysteine (r2 = 0.42-0.69; P < 0.001) and S-adenosyl-l-methionine/S-adenosyl-l-homocysteine ratios (r2 = 0.56-0.65; P < 0.001) in cerebrospinal fluid and levels and ratios in cortex, cerebellum and spinal cord. The levels of S-adenosyl-l-methionine did not show a significant correlation. 3. We conclude that the ratio of these metabolites in the cerebrospinal fluid may reflect the ratio in the central nervous system and we suggest that this may also be true in human tissues. This finding will permit the determination of the probable methylation ratio in the central nervous system in human conditions, such as vitamin B12 deficiency and acquired immune deficiency syndrome, where a similar myelopathy occurs to that seen in the nitrous oxide-treated pig. All three myelopathies may arise from an inhibition of methyltransferases involved in the synthesis of myelin that would occur when the methylation ratio is reduced.

Cytology of Equine Cerebrospinal Fluid

1983 ◽  
Vol 20 (5) ◽  
pp. 553-562 ◽  
Author(s):  
J. Beech
Keyword(s):  
Spinal Cord ◽  
Central Nervous System ◽  
Cerebrospinal Fluid ◽  
Nervous System ◽  
Axonal Degeneration ◽  
Mononuclear Cells ◽  
Lethal Dose ◽  
Cord Compression ◽  
The Central Nervous System ◽  
Mitotic Figures

The cytology of cerebrospinal fluid samples from horses is described. The samples were obtained from 24 normal horses. 35 horses with axonal degeneration and/or spinal cord compression. 29 horses with encephalomyelitis, 14 horses with other lesions of the nervous system, and eight horses with signs of neurologic dysfunction of undetermined origin. (Three of the latter were suspected botulinum intoxications.) Fluid was aspirated from the atlanto-occipital space following general anesthesia or immediately after a lethal dose of barbiturate. In two horses, fluid also was aspirated from the lumbosacral space. Small mononuclear cells were predominant in normal horses, and in most horses with axonal degeneration and encephalomyelitis. Several horses with encephalomyelitis also had neutrophils, eosinophils, and some mitotic figures. Although the cytologic findings were abnormal in many of the horses with disease of the central nervous system, in most horses the cytologic findings were normal.

Inability of Cerebrospinal Fluid to Nourish the Spinal Cord

1955 ◽  
Vol 184 (1) ◽  
pp. 220-222 ◽  
Author(s):  
Peter H. Wolff ◽  
Robert D. Tschirgi
Keyword(s):  
Spinal Cord ◽  
Central Nervous System ◽  
Cerebrospinal Fluid ◽  
Nervous System ◽  
Spinal Reflexes ◽  
Pupillary Dilatation ◽  
Spinal Subarachnoid Space ◽  
The Central Nervous System ◽  
High Concentrations ◽  
Pupillary Size

Cephalad perfusion with Tyrode's solution of the spinal subarachnoid space between a lumbar and cisternal tap in anesthetized cats had no effect on spinal reflexes, respiration or pupillary size for periods of 8 hours. Alteration of Ca++ or K+ concentration in the perfusate produced immediate changes in these indices, indicating the availability of the perfusate to neural elements. The onset and course of patellar areflexia, respiratory depression and pupillary dilatation resulting from i.v. insulin-induced hypoglycemia could not be influenced by including high concentrations of glucose, glutamate, succinate or a combination of these latter two in the subarachnoid perfusate. It is concluded that the cerebrospinal fluid cannot act as a sufficient medium for transport from the blood of nutrient substrates essential for maintaining function in the central nervous system.

Central Nerve System Impairment, AMA Guides, Sixth Edition: An Overview

2018 ◽  
Vol 23 (1) ◽  
pp. 10-13
Author(s):  
James B. Talmage ◽  
Jay Blaisdell
Keyword(s):  
Spinal Cord ◽  
Central Nervous System ◽  
Nervous System ◽  
Neurological Impairment ◽  
Sixth Edition ◽  
Central Nerve System ◽  
The Central Nervous System ◽  
The One ◽  
Nerve System ◽  
The Brain

Abstract Injuries that affect the central nervous system (CNS) can be catastrophic because they involve the brain or spinal cord, and determining the underlying clinical cause of impairment is essential in using the AMA Guides to the Evaluation of Permanent Impairment (AMA Guides), in part because the AMA Guides addresses neurological impairment in several chapters. Unlike the musculoskeletal chapters, Chapter 13, The Central and Peripheral Nervous System, does not use grades, grade modifiers, and a net adjustment formula; rather the chapter uses an approach that is similar to that in prior editions of the AMA Guides. The following steps can be used to perform a CNS rating: 1) evaluate all four major categories of cerebral impairment, and choose the one that is most severe; 2) rate the single most severe cerebral impairment of the four major categories; 3) rate all other impairments that are due to neurogenic problems; and 4) combine the rating of the single most severe category of cerebral impairment with the ratings of all other impairments. Because some neurological dysfunctions are rated elsewhere in the AMA Guides, Sixth Edition, the evaluator may consult Table 13-1 to verify the appropriate chapter to use.

CHAPTER 9: Immunology of TBEV-Infections

2020 ◽  
Keyword(s):  
Central Nervous System ◽  
T Cells ◽  
Cerebrospinal Fluid ◽  
Nervous System ◽  
Nk Cells ◽  
Peripheral Blood ◽  
Sample Collection ◽  
Tick Borne Encephalitis ◽  
Viral Infectious Disease ◽  
The Central Nervous System

Tick-borne encephalitis (TBE) is a viral infectious disease of the central nervous system caused by the tick-borne encephalitis virus (TBEV). TBE is usually a biphasic disease and in humans the virus can only be detected during the first (unspecific) phase of the disease. Pathogenesis of TBE is not well understood, but both direct viral effects and immune-mediated tissue damage of the central nervous system may contribute to the natural course of TBE. The effect of TBEV on the innate immune system has mainly been studied in vitro and in mouse models. Characterization of human immune responses to TBEV is primarily conducted in peripheral blood and cerebrospinal fluid, due to the inaccessibility of brain tissue for sample collection. Natural killer (NK) cells and T cells are activated during the second (meningo-encephalitic) phase of TBE. The potential involvement of other cell types has not been examined to date. Immune cells from peripheral blood, in particular neutrophils, T cells, B cells and NK cells, infiltrate into the cerebrospinal fluid of TBE patients.

METABOLIC STUDIES WITH 131I-LABELED THYROXINE. II.

1963 ◽  
Vol 44 (3) ◽  
pp. 475-480 ◽  
Author(s):  
R. Grinberg
Keyword(s):  
Spinal Cord ◽  
Central Nervous System ◽  
Nervous System ◽  
Optic Nerve ◽  
Pituitary Gland ◽  
Time Interval ◽  
Time Intervals ◽  
Pituitary Glands ◽  
The Central Nervous System ◽  
Tentative Explanation

ABSTRACT Radiologically thyroidectomized female Swiss mice were injected intraperitoneally with 131I-labeled thyroxine (T4*), and were studied at time intervals of 30 minutes and 4, 28, 48 and 72 hours after injection, 10 mice for each time interval. The organs of the central nervous system and the pituitary glands were chromatographed, and likewise serum from the same animal. The chromatographic studies revealed a compound with the same mobility as 131I-labeled triiodothyronine in the organs of the CNS and in the pituitary gland, but this compound was not present in the serum. In most of the chromatographic studies, the peaks for I, T4 and T3 coincided with those for the standards. In several instances, however, such an exact coincidence was lacking. A tentative explanation for the presence of T3* in the pituitary gland following the injection of T4* is a deiodinating system in the pituitary gland or else the capacity of the pituitary gland to concentrate T3* formed in other organs. The presence of T3* is apparently a characteristic of most of the CNS (brain, midbrain, medulla and spinal cord); but in the case of the optic nerve, the compound is not present under the conditions of this study.

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