Stability of mRNA/Cationic Lipid Lipoplexes in Human and Rat Cerebrospinal Fluid: Methods and Evidence for Nonviral mRNA Gene Delivery to the Central Nervous System

2003 ◽  
Vol 14 (3) ◽  
pp. 191-202 ◽  
Author(s):  
Dua M. Anderson ◽  
Leon L. Hall ◽  
Anitha R. Ayyalapu ◽  
Van R. Irion ◽  
Michael H. Nantz ◽  
...  

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.


Life ◽  
2021 ◽  
Vol 11 (4) ◽  
pp. 300
Author(s):  
Petr Kelbich ◽  
Aleš Hejčl ◽  
Jan Krejsek ◽  
Tomáš Radovnický ◽  
Inka Matuchová ◽  
...  

Extravasation of blood in the central nervous system (CNS) represents a very strong damaged associated molecular patterns (DAMP) which is followed by rapid inflammation and can participate in worse outcome of patients. We analyzed cerebrospinal fluid (CSF) from 139 patients after the CNS hemorrhage. We compared 109 survivors (Glasgow Outcome Score (GOS) 5-3) and 30 patients with poor outcomes (GOS 2-1). Statistical evaluations were performed using the Wilcoxon signed-rank test and the Mann–Whitney U test. Almost the same numbers of erythrocytes in both subgroups appeared in days 0–3 (p = 0.927) and a significant increase in patients with GOS 2-1 in days 7–10 after the hemorrhage (p = 0.004) revealed persistence of extravascular blood in the CNS as an adverse factor. We assess 43.3% of patients with GOS 2-1 and only 27.5% of patients with GOS 5-3 with low values of the coefficient of energy balance (KEB < 15.0) in days 0–3 after the hemorrhage as a trend to immediate intensive inflammation in the CNS of patients with poor outcomes. We consider significantly higher concentration of total protein of patients with GOS 2-1 in days 0–3 after hemorrhage (p = 0.008) as the evidence of immediate simultaneously manifested intensive inflammation, swelling of the brain and elevation of intracranial pressure.


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

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.


1927 ◽  
Vol 23 (11) ◽  
pp. 1182-1182
Author(s):  
D. K. Bogoroditsky

The technique of this reaction, suggested by two Japanese authors, Takata and Aga, in 1926, consists in adding 1 drop of a 10% Na carbonici solution and 0.3 of a freshly prepared mixture of equal parts 0.5% sulfa solution and 0.02% fuchsin (non-acid) solution to 1 cc of liquid. The mixture is shaken well and left in a test tube, and examined now after shaking, after h, after h, and after 24 h. Having tested this reaction in 60 patients, D.K. Bogoroditsky found that it is a very subtle indicator of the state of the central nervous system.


Neurosurgery ◽  
2015 ◽  
Vol 78 (3) ◽  
pp. 343-352 ◽  
Author(s):  
Arnault Tauziede-Espariat ◽  
Andre Maues de Paula ◽  
Melanie Pages ◽  
Annie Laquerriere ◽  
Emilie Caietta ◽  
...  

Abstract BACKGROUND: Primary leptomeningeal gliomatosis (PLG) is a poorly recognized tumor of the central nervous system. OBJECTIVE: To describe the histopathological, immunohistochemical, and molecular features of PLG. METHODS: Results of our multicentric retrospective study of 6 PLG cases (3 pediatric and 3 adult) were compared with literature data. RESULTS: The mean age was 54.7 years for adults and 8.7 years for children, with 3 males and 3 females. Clinical symptoms were nonspecific. Cerebrospinal fluid analyses showed a high protein level often associated with pleocytosis but without neoplastic cells. On neuroimaging, diffuse leptomeningeal enhancement and hydrocephalus were observed, except in 1 case. PLG was mostly misinterpreted as infectious or tumoral meningitis. The first biopsy was negative in 50% of cases. Histopathologically, PLG cases corresponded to 1 oligodendroglioma without 1p19q codeletion and 5 astrocytomas without expression of p53. No immunostaining for IDH1R132H and no mutations of IDH1/2 and H3F3A genes were found. Overall survival was highly variable (2-82 months) but seems to be increased in children treated with chemotherapy. CONCLUSION: This study shows the difficulties of PLG diagnosis. The challenge is to achieve an early biopsy to establish a diagnosis and to begin a treatment, but the prognosis remains poor. PLG seems to have a different molecular and immunohistochemical pattern compared with intraparenchymal malignant gliomas.


2015 ◽  
Vol 59 (4) ◽  
pp. 339-344 ◽  
Author(s):  
Juan Xing ◽  
Lisa Radkay ◽  
Sara E. Monaco ◽  
Christine G. Roth ◽  
Liron Pantanowitz

Lyme disease can affect the central nervous system causing a B-cell-predominant lymphocytic pleocytosis. Since most reactions to infection in the cerebrospinal fluid (CSF) are typically T-cell predominant, a B-cell-predominant lymphocytosis raises concern for lymphoma. We present 3 Lyme neuroborreliosis cases in order to illustrate the challenging cytomorphological and immunophenotypic features of their CSF specimens. Three male patients who presented with central nervous system manifestations were diagnosed with Lyme disease. The clinical presentation, laboratory tests, CSF cytological examination and flow-cytometric studies were described for each case. CSF cytology showed lymphocytic pleocytosis with increased plasmacytoid cells and/or plasma cells. Flow cytometry showed the presence of polytypic B lymphocytes with evidence of plasmacytic differentiation in 2 cases. In all cases, Lyme disease was confirmed by the Lyme screening test and Western blotting. In such cases of Lyme neuroborreliosis, flow cytometry of CSF samples employing plasmacytic markers and cytoplasmic light-chain analysis is diagnostically helpful to exclude lymphoma.


2019 ◽  
Vol 11 (1) ◽  
pp. 41-45
Author(s):  
L. V. Pypa ◽  
R. V. Svistilnik ◽  
Yu. N. Lysytsia ◽  
K. Yu. Romanchuk ◽  
I. V. Odarchuk

Aim of work – to analyze the etiological structure, epidemiological structure, social-demographic features and the nature of the development of complications of the central nervous system in aseptic meningitis in children in Khmelnitskyi region for the period 2004-2017.Materials and methods. It was conducted a prospective analysis of 208 cases of aseptic meningitis in children of whom 138 people were boys and 70 people were girls. The etiology of the disease was determined by studying cerebrospinal fluid using PCR method. Complications of the central nervous system were diagnosed on the basis of the clinical picture and CT or MRI scans. The analytical method was used to conduct the analysis of the received data.Results. The highest seasonal increase of the incidence was from August to October and it was 65.6% with its peak in September (24.0%). The clinical picture was characterized by a moderate trend in 71.2% of cases and in 28.8% by a severe course. In 100% of cases the disease began with a fever, headache (83.6%), vomiting (76.9%), abdominal pain with diarrhea (6.2%), epileptic seizures (0.9%). The average level of cytosis was 269.4±196.7 cells/mm3with a predominance of lymphocytes and the average protein level in cerebrospinal fluid was 73 ± 36 mg/dl. The etiological factor was established in 18 (8.6%) patients.Conclusions. Enterovirus remains to be the main pathogen which was determined in 72.2% of cases. The second place was taken by herpes viruses (22.2% of cases), the third place was given to the mumps virus (5.6% of cases) (in etiologically verified cases). In most cases the disease ended in complete recovery but in 47 (22.6%) patients the complications were observed. The prevalence of aseptic meningitis among children in Khmelnitskyi region was 6.2 per 100,000 children, and males outnumbered females by a 2:1 ratio.


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