Apparatus for long-term ventricular access in the awake canine

1986 ◽  
Vol 61 (1) ◽  
pp. 368-372 ◽  
Author(s):  
E. C. Ellison ◽  
T. T. Pappas ◽  
W. G. Pace ◽  
T. M. O'Dorisio
Keyword(s):  
Molecular Weight ◽  
Central Nervous System ◽  
Cerebrospinal Fluid ◽  
Nervous System ◽  
Peripheral Blood ◽  
Ventricular System ◽  
Blood Levels ◽  
Maximum Frequency ◽  
Fatal Complications

An apparatus is described that permits lateral ventricular cerebrospinal fluid (CSF) to be sampled or an infusion to be performed into the ventricular system in the awake canine. The device has been used in 25 dogs. CSF was sampled, and experiments involving infusions into the lateral ventricle were performed over a 6- to 24-mo period. The maximum frequency of ventricular cannulation using the apparatus was once per week. Complications occurred in 10 dogs, all of which were successfully treated, permitting experiments to continue. Three fatal complications included meningitis in one animal at 24 mo and seizures in two animals, causing death at 12 and 18 mo. Administration of peptides, bombesin, and somatostatin into the ventricular system was followed by prompt rises in bombesin and somatostatin radioimmunoactivity in the CSF. There were no parallel increases of these peptides in the peripheral blood levels up to 2 h after infusion. Peptides of this molecular weight infused with this apparatus do not seem to leak into peripheral blood. The apparatus permits repeated ventricular cannulation in the awake canine for sampling of CSF and administration of biological substances to determine specific central nervous system action.

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.

scholarly journals Persistent cognitive impairment associated with cerebrospinal fluid anti-SARS-CoV-2 antibodies six months after mild COVID-19

2021 ◽  
Vol 3 (1) ◽  
Author(s):  
Max Borsche ◽  
Dirk Reichel ◽  
Anja Fellbrich ◽  
Anne S. Lixenfeld ◽  
Johann Rahmöller ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Cerebrospinal Fluid ◽  
Nervous System ◽  
Cognitive Impairment ◽  
Female Patient ◽  
Acute Phase ◽  
Neuropsychological Testing ◽  
Important Challenge ◽  
Central Nervous System Invasion

AbstractNeurological long-term sequelae are increasingly considered an important challenge in the recent COVID-19 pandemic. However, most evidence for neurological symptoms after SARS-CoV-2 infection and central nervous system invasion of the virus stems from individuals severely affected in the acute phase of the disease. Here, we report long-lasting cognitive impairment along with persistent cerebrospinal fluid anti-SARS-CoV-2 antibodies in a female patient with unremarkable standard examination 6 months after mild COVID-19, supporting the implementation of neuropsychological testing and specific cerebrospinal fluid investigation also in patients with a relatively mild acute disease phase.

Chapter 9: Immunology of TBEV-Infection

2021 ◽  
Author(s):  
Sara Gredmark-Russ ◽  
Renata Varnaite
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.

scholarly journals Targeting the Choroid Plexuses for Protein Drug Delivery

Pharmaceutics ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 963
Author(s):  
Mark A. Bryniarski ◽  
Tianjing Ren ◽  
Abbas R. Rizvi ◽  
Anthony M. Snyder ◽  
Marilyn E. Morris
Keyword(s):  
Drug Delivery ◽  
Central Nervous System ◽  
Cerebrospinal Fluid ◽  
Nervous System ◽  
Choroid Plexus ◽  
Protein Therapeutics ◽  
Ventricular System ◽  
Ependymal Cells ◽  
Choroid Plexuses ◽  
Choroid Plexus Epithelial

Delivery of therapeutic agents to the central nervous system is challenged by the barriers in place to regulate brain homeostasis. This is especially true for protein therapeutics. Targeting the barrier formed by the choroid plexuses at the interfaces of the systemic circulation and ventricular system may be a surrogate brain delivery strategy to circumvent the blood-brain barrier. Heterogenous cell populations located at the choroid plexuses provide diverse functions in regulating the exchange of material within the ventricular space. Receptor-mediated transcytosis may be a promising mechanism to deliver protein therapeutics across the tight junctions formed by choroid plexus epithelial cells. However, cerebrospinal fluid flow and other barriers formed by ependymal cells and perivascular spaces should also be considered for evaluation of protein therapeutic disposition. Various preclinical methods have been applied to delineate protein transport across the choroid plexuses, including imaging strategies, ventriculocisternal perfusions, and primary choroid plexus epithelial cell models. When used in combination with simultaneous measures of cerebrospinal fluid dynamics, they can yield important insight into pharmacokinetic properties within the brain. This review aims to provide an overview of the choroid plexuses and ventricular system to address their function as a barrier to pharmaceutical interventions and relevance for central nervous system drug delivery of protein therapeutics. Protein therapeutics targeting the ventricular system may provide new approaches in treating central nervous system diseases.

scholarly journals Diagnosis of Central Nervous System Tuberculosis by T-Cell-Based Assays on Peripheral Blood and Cerebrospinal Fluid Mononuclear Cells

2008 ◽  
Vol 15 (9) ◽  
pp. 1356-1362 ◽  
Author(s):  
Sung-Han Kim ◽  
Kon Chu ◽  
Su-Jin Choi ◽  
Kyoung-Ho Song ◽  
Hong-Bin Kim ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Cerebrospinal Fluid ◽  
Nervous System ◽  
Sensitivity And Specificity ◽  
Mononuclear Cell ◽  
Peripheral Blood ◽  
Elispot Assay ◽  
Mononuclear Cells ◽  
Clinical Manifestations ◽  
Peripheral Blood Mononuclear

ABSTRACT In active tuberculosis (TB), Mycobacterium tuberculosis-specific T cells are compartmentalized more to the site of infection than to the circulating blood. Therefore, an M. tuberculosis-specific enzyme-linked immunospot (ELISPOT) assay with samples from the site of infection may permit a more sensitive or specific diagnosis of active central nervous system (CNS) TB than that achieved by the assay with blood alone. Therefore, we prospectively evaluated the usefulness of circulating and compartmentalized mononuclear cell (MC; i.e., peripheral blood mononuclear cell [PBMC] and cerebrospinal fluid [CSF] MC)-based ELISPOT assays (i.e., the T-SPOT.TB test) for the diagnosis of active TB in patients with suspected CNS TB. The clinical categories of CNS TB were classified as described previously (G. E. Thwaites, T. T. Chau, K. Stepniewska, N. H. Phu, L. V. Chuong, D. X. Sinh, N. J. White, C. M. Parry, and J. J. Farrar, Lancet 360:1287-1292, 2002). Thirty-seven patients with suspected CNS TB were enrolled over a 12-month period. Of these, 31 (84%) showed clinical manifestations of suspected TB meningitis and 6 (16%) gave indications of intracranial tuberculoma with disseminated TB. The final clinical categories of the 37 patients with suspected CNS TB were as follows: 12 (32%) were classified as having CNS TB (7 with confirmed TB, 3 with probable TB, and 2 with possible TB) and 25 (68%) were classified as not having active TB. The sensitivity and specificity of the PBMC ELISPOT assay were 91% (95% confidence interval [CI], 59% to 100%) and 63% (95% CI, 41% to 81%), respectively. By comparison, the sensitivity and specificity of the CSF MC ELISPOT assay were 75% (95% CI, 19% to 99%) and 75% (95% CI, 43% to 95%), respectively. When the ratio of the CSF MC ELISPOT assay results to the PBMC ELISPOT results was 2 or more, the sensitivity and specificity were 50% (95% CI, 7% to 93%) and 100% (95% CI, 74% to 100%), respectively. The ELISPOT assay with PBMCs and CSF MCs is a useful adjunct to the current tests for the diagnosis of CNS TB.

scholarly journals Successful Treatment with Intrathecal Tocilizumab(IL-6 antibody) for 2 Cases of Graft-Versus Host Disease of the Central Nervous System after a Second Allogeneic HSCT from Haploidentical Donor

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 5730-5730
Author(s):  
Ruirui Gui ◽  
Juanjuan Zhao ◽  
Yingling Zu ◽  
Lu Han ◽  
Yanli Zhang ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Cerebrospinal Fluid ◽  
Nervous System ◽  
Cell Transplantation ◽  
Graft Versus Host Disease ◽  
Peripheral Blood ◽  
Intrathecal Injection ◽  
Graft Versus Host ◽  
Hematopoietic Recovery ◽  
The Central Nervous System

Abstract Graft-versus-host disease (GVHD) of central nervous system (CNS) is a rare complication after allogeneic hematopoietic cell transplantation (allo-HSCT), which is easily misdiagnosed and has limited treatment and poor efficacy. In this study, we reported two children(1 case of severe aplastic anemia and 1 case of acute myeloid leukemia) who were subjected to the secondary haploid hematopoietic stem cell transplantation of another door after the first implantation failure. Two patients developed epileptic seizures during hematopoietic recovery. Peripheral blood and cerebrospinal fluid cytokines were detected and diagnosed as acute GVHD in the central nervous system. The cytokine elevation is mainly IL-6(IL-6 level in peripheral blood was 2276.25 pg/ml, and in cerebrospinal fluid was 2353.89pg/ml of case 1). We administered multiply consecutive plasmapheresis, intravenous infusion of tocilizumab combined with intrathecal injection of tocilizumab and dexamethasone. The epileptic symptoms of 2 cases are effectively controlled after the first dose. The IL-6 levels in peripheral blood and cerebrospinal fluid of both patients decreased significantly after 4(IL-6 level in peripheral blood was 6.74 pg/ml, and in cerebrospinal fluid was 195.72pg/ml of case 1) and 5 doses, respectively. Central nervous system aGVHD is prone to hematopoietic recovery after secondary transplantation; intrathecal injection of tocilizumab is safe and effective in the treatment of central nervous system aGVHD with elevated IL-6 mainly, which is worth further exploring. Figure. Figure. Disclosures No relevant conflicts of interest to declare.

Chapter 9: Immunology of TBEV-Infection

2019 ◽  
Author(s):  
Sara Gredmark-Russ ◽  
Renata Varnaite
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 (meningoencephalitic) 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.

Intravenous delivery of adeno-associated viral gene therapy in feline GM1 gangliosidosis

Brain ◽  
2021 ◽  
Author(s):  
Amanda L Gross ◽  
Heather L Gray-Edwards ◽  
Cassie N Bebout ◽  
Nathan L Ta ◽  
Kayly Nielsen ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Central Nervous System ◽  
Cerebrospinal Fluid ◽  
Nervous System ◽  
Galactosidase Activity ◽  
Gm1 Gangliosidosis ◽  
The Central Nervous System ◽  
Imaging And Spectroscopy ◽  
The Brain

Abstract GM1 gangliosidosis is a fatal neurodegenerative disease caused by a deficiency of lysosomal β-galactosidase. In its most severe form, GM1 gangliosidosis causes death by 4 years of age, and no effective treatments exist. Previous work has shown that injection of the brain parenchyma with an adeno-associated viral vector provides pronounced therapeutic benefit in a feline GM1 model. To develop a less invasive treatment for the brain and increase systemic biodistribution, intravenous injection of AAV9 was evaluated. AAV9 expressing feline β-galactosidase was intravenously administered at 1.5x1013 vector genomes/kilogram body weight to six GM1 cats at approximately 1 month of age. The animals were divided into two cohorts: 1) a long-term group, which was followed to humane endpoint, and 2) a short-term group, which was analyzed 16-weeks post treatment. Clinical assessments included neurological exams, cerebrospinal fluid and urine biomarkers, and 7-Telsa magnetic resonance imaging and spectroscopy. Postmortem analysis included β-galactosidase and virus distribution, histological analysis, and ganglioside content. Untreated GM1 animals survived 8.0 ± 0.6 months while intravenous treatment increased survival to an average of 3.5 years (n = 2) with substantial improvements in quality of life and neurologic function. Neurological abnormalities, which in untreated animals progress to the inability to stand and debilitating neurological disease by 8 months of age, were mild in all treated animals. Cerebrospinal fluid biomarkers were normalized, indicating decreased central nervous system cell damage in the treated animals. Urinary glycosaminoglycans decreased to normal levels in the long-term cohort. Magnetic resonance imaging and spectroscopy showed partial preservation of the brain in treated animals, which was supported by postmortem histological evaluation. β-galactosidase activity was increased throughout the central nervous system, reaching carrier levels in much of the cerebrum and normal levels in the cerebellum, spinal cord and cerebrospinal fluid. Ganglioside accumulation was significantly reduced by treatment. Peripheral tissues such as heart, skeletal muscle, and sciatic nerve also had normal β-galactosidase activity in treated GM1 cats. GM1 histopathology was largely corrected with treatment. There was no evidence of tumorigenesis or toxicity. Restoration of β-galactosidase activity in the central nervous system and peripheral organs by intravenous gene therapy led to profound increases in lifespan and quality of life in GM1 cats. This data supports the promise of intravenous gene therapy as a safe, effective treatment for GM1 gangliosidosis.

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