scholarly journals In Vitro and In Vivo Characterization of a Mouse Adenovirus Type 1 Early Region 3 Null Mutant

1999 ◽  
Vol 73 (10) ◽  
pp. 8640-8646 ◽  
Author(s):  
Angela N. Cauthen ◽  
Corrie C. Brown ◽  
Katherine R. Spindler
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Lethal Dose ◽  
Adenovirus Type ◽  
Null Mutant ◽  
Early Region ◽  
The Central Nervous System ◽  
Early Region 3

ABSTRACT Previous attempts to construct a mouse adenovirus type 1 early region 3 (E3) null mutant by initiator codon mutagenesis were unsuccessful because one of the E3 proteins, gp11K, is synthesized as a fusion protein from a late viral mRNA (A. N. Cauthen and K. R. Spindler, Virology 259:119–128, 1999). Therefore, a different mutagenesis strategy was employed that inserted termination codons into all three reading frames of the E3 proteins. This strategy produced a mutant, pmE314, that was null for the expression of E3 proteins as determined by immunoprecipitation with E3-specific antisera. This mutant grew as well as wild-type (wt) virus in both 3T6 mouse fibroblasts and mouse brain microvascular endothelial cells. However, the 50% lethal dose for pmE314 in adult NIH Swiss outbred mice was approximately 6 log units higher than that of wt virus, indicating that pmE314 was less virulent in mice. In situ hybridization experiments revealed that the absence of the E3 proteins did not alter the tropism of the mutant virus from that of wt virus. When the histopathology was evaluated, the characteristics of the pmE314 infection at both doses administered were strikingly different from those exhibited by wt virus. The central nervous system of wt-infected mice exhibited damage to the endothelium and recruitment of inflammatory cells, whereas the central nervous system of pmE314-infected mice showed no inflammatory response and only mild signs of endothelial damage.

scholarly journals LATENT HERPES SIMPLEX VIRUS IN THE CENTRAL NERVOUS SYSTEM OF RABBITS AND MICE

1973 ◽  
Vol 138 (3) ◽  
pp. 740-744 ◽  
Author(s):  
F. B. Knotts ◽  
M. L. Cook ◽  
J. G. Stevens
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Organ Cultures ◽  
The Central Nervous System ◽  
Simplex Virus ◽  
The Brain

Herpes simplex virus (HSV) type 1 induces a long-standing latent infection in the central nervous system of mice and rabbits. The infection was extablished in the brain stems of rabbits after corneal inoculation of the virus, and in the spinal cords of mice after rear footpad infection. In these animals, infectious virus could not be recovered by direct isolation from tissues; it was detected only after the tissues were maintained as organ cultures in vitro.

Development and regeneration in the central nervous system

1990 ◽  
Vol 327 (1239) ◽  
pp. 127-143 ◽  
Keyword(s):  
Stem Cells ◽  
Central Nervous System ◽  
Nervous System ◽  
Progenitor Cells ◽  
Progenitor Cell ◽  
Cell Types ◽  
The Central Nervous System

As part of our attempts to understand principles that underly organism development, we have been studying the development of the rat optic nerve. This simple tissue is composed of three glial cell types derived from two distinct cellular lineages. Type-1 astrocytes appear to be derived from a monopotential neuroepithelial precursor, whereas type-2 astrocytes and oligodendrocytes are derived from a common oligodendrocyte-type-2 astrocyte (O-2A) progenitor cell. Type-1 astrocytes modulate division and differentiation of O-2A progenitor cells through secretion of platelet-derived growth factor, and can themselves be stimulated to divide by peptide mitogens and through stimulation of neurotransmitter receptors. In vitro analysis indicates that many dividing O-2A progenitors derived from optic nerves of perinatal rats differentiate symmetrically and clonally to give rise to oligodendrocytes, or can be induced to differentiate into type-2 astrocytes. O-2A perinatal progenitors can also differentiate to form a further O-2A lineage cell, the O-2A adult progenitor, which has properties specialized for the physiological requirements of the adult nervous system. In particular, O-2A adult progenitors have many of the features of stem cells, in that they divide slowly and asymmetrically and appear to have the capacity for extended self-renewal. The apparent derivation of a slowly and asymmetrically dividing cell, with properties appropriate for homeostatic maintenance of existing populations in the mature animal, from a rapidly dividing cell with properties suitable for the rapid population and myelination of central nervous system (CNS) axon tracts during early development, offers novel and unexpected insights into the possible origin of self-renewing stem cells and also into the role that generation of stem cells may play in helping to terminate the explosive growth of embryogenesis. Moreover, the properties of O-2A adult progenitor cells are consistent with, and may explain, the failure of successful myelin repair in conditions such as multiple sclerosis, and thus seem to provide a cellular biological basis for understanding one of the key features of an important human disease.

scholarly journals The Role of Mouse Adenovirus Type 1 Early Region 1A in Acute and Persistent Infections in Mice

1998 ◽  
Vol 72 (7) ◽  
pp. 5699-5706 ◽  
Author(s):  
Kimberley Smith ◽  
Corrie C. Brown ◽  
Katherine R. Spindler
Keyword(s):  
Persistent Infection ◽  
Mononuclear Cells ◽  
Lethal Dose ◽  
Pcr Amplification ◽  
Adenovirus Type ◽  
Wild Type Virus ◽  
Null Mutant ◽  
Wild Type ◽  
Early Region

ABSTRACT Mouse adenovirus type 1 (MAV-1) early region 1A (E1A) viral mutants were used to determine the importance of this region in pathogenesis and establishment of a persistent infection in the natural host. Lethal dose analysis with adult male Swiss outbred mice revealed a significant reduction in virulence for all of the E1A mutants. During acute infections with 105 PFU of virus, an E1A null mutant,pmE109, was found in the same organs (brain, spleen, and spinal cord) and the same cell types (endothelial cells and mononuclear cells in lymphoid tissue) as wild-type virus. Another null mutant,pmE112, was detected in the same organs but in lower numbers. However, when mice were given a lower dose, 1 PFU,pmE109 and pmE112 reached none of the target organs analyzed by 14 days postinfection (p.i.). The absence of E1A did not hinder the ability of MAV-1 to establish a persistent infection. Viral nucleic acid was detected by PCR amplification or in situ hybridization in the kidneys, brains, spleens, and prefemoral lymph nodes of mice infected with wild-type or mutant virus up to 55 weeks p.i. The brain, spleen, and lymph node are recognized sites of acute viral infection but are previously unrecognized sites for MAV-1 persistence. Evidence for the potential reactivation of persistent MAV-1 infections is also presented.

Neural Stem Cells to Glial Cells an Important Factor for Brain Injury

2020 ◽  
Author(s):  
Prithiv K R Kumar
Keyword(s):  
Stem Cells ◽  
Central Nervous System ◽  
Nervous System ◽  
Neural Stem Cells ◽  
Glial Cells ◽  
Brain Injuries ◽  
The Body ◽  
The Central Nervous System ◽  
Near Future

Stem cells have the capacity to differentiate into any type of cell or organ. Stems cell originate from any part of the body, including the brain. Brain cells or rather neural stem cells have the capacitive advantage of differentiating into the central nervous system leading to the formation of neurons and glial cells. Neural stem cells should have a source by editing DNA, or by mixings chemical enzymes of iPSCs. By this method, a limitless number of neuron stem cells can be obtained. Increase in supply of NSCs help in repairing glial cells which in-turn heal the central nervous system. Generally, brain injuries cause motor and sensory deficits leading to stroke. With all trials from novel therapeutic methods to enhanced rehabilitation time, the economy and quality of life is suppressed. Only PSCs have proven effective for grafting cells into NSCs. Neurons derived from stem cells is the only challenge that limits in-vitro usage in the near future.

scholarly journals Beyond Oncological Hyperthermia: Physically Drivable Magnetic Nanobubbles as Novel Multipurpose Theranostic Carriers in the Central Nervous System

Molecules ◽  
2020 ◽  
Vol 25 (9) ◽  
pp. 2104 ◽  
Author(s):  
Eleonora Ficiarà ◽  
Shoeb Anwar Ansari ◽  
Monica Argenziano ◽  
Luigi Cangemi ◽  
Chiara Monge ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Brain Tumors ◽  
Ad Hoc ◽  
Superparamagnetic Iron Oxide ◽  
Conventional Radiotherapy ◽  
The Central Nervous System ◽  
Magnetic Resonance Imaging Mri ◽  
The Brain

Magnetic Oxygen-Loaded Nanobubbles (MOLNBs), manufactured by adding Superparamagnetic Iron Oxide Nanoparticles (SPIONs) on the surface of polymeric nanobubbles, are investigated as theranostic carriers for delivering oxygen and chemotherapy to brain tumors. Physicochemical and cyto-toxicological properties and in vitro internalization by human brain microvascular endothelial cells as well as the motion of MOLNBs in a static magnetic field were investigated. MOLNBs are safe oxygen-loaded vectors able to overcome the brain membranes and drivable through the Central Nervous System (CNS) to deliver their cargoes to specific sites of interest. In addition, MOLNBs are monitorable either via Magnetic Resonance Imaging (MRI) or Ultrasound (US) sonography. MOLNBs can find application in targeting brain tumors since they can enhance conventional radiotherapy and deliver chemotherapy being driven by ad hoc tailored magnetic fields under MRI and/or US monitoring.

scholarly journals Non-Oncological Neuroradiological Manifestations in NF1 and Their Clinical Implications

Cancers ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1831
Author(s):  
Camilla Russo ◽  
Carmela Russo ◽  
Daniele Cascone ◽  
Federica Mazio ◽  
Claudia Santoro ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Structural Organization ◽  
Neurofibromatosis Type ◽  
Review Article ◽  
Tumor Suppressor Protein ◽  
Clinical Implications ◽  
Nf1 Gene ◽  
The Central Nervous System

Neurofibromatosis type 1 (NF1), the most frequent phakomatosis and one of the most common inherited tumor predisposition syndromes, is characterized by several manifestations that pervasively involve central and peripheral nervous system structures. The disorder is due to mutations in the NF1 gene, which encodes for the ubiquitous tumor suppressor protein neurofibromin; neurofibromin is highly expressed in neural crest derived tissues, where it plays a crucial role in regulating cell proliferation, differentiation, and structural organization. This review article aims to provide an overview on NF1 non-neoplastic manifestations of neuroradiological interest, involving both the central nervous system and spine. We also briefly review the most recent MRI functional findings in NF1.

scholarly journals Effects of Platelet-Rich Plasma on Cellular Populations of the Central Nervous System: The Influence of Donor Age

2021 ◽  
Vol 22 (4) ◽  
pp. 1725
Author(s):  
Diego Delgado ◽  
Ane Miren Bilbao ◽  
Maider Beitia ◽  
Ane Garate ◽  
Pello Sánchez ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Cellular Response ◽  
Platelet Rich Plasma ◽  
Biological Response ◽  
In Vitro Models ◽  
Molecular Composition ◽  
Cellular Models ◽  
The Central Nervous System

Platelet-rich plasma (PRP) is a biologic therapy that promotes healing responses across multiple medical fields, including the central nervous system (CNS). The efficacy of this therapy depends on several factors such as the donor’s health status and age. This work aims to prove the effect of PRP on cellular models of the CNS, considering the differences between PRP from young and elderly donors. Two different PRP pools were prepared from donors 65–85 and 20–25 years old. The cellular and molecular composition of both PRPs were analyzed. Subsequently, the cellular response was evaluated in CNS in vitro models, studying proliferation, neurogenesis, synaptogenesis, and inflammation. While no differences in the cellular composition of PRPs were found, the molecular composition of the Young PRP showed lower levels of inflammatory molecules such as CCL-11, as well as the presence of other factors not found in Aged PRP (GDF-11). Although both PRPs had effects in terms of reducing neural progenitor cell apoptosis, stabilizing neuronal synapses, and decreasing inflammation in the microglia, the effect of the Young PRP was more pronounced. In conclusion, the molecular composition of the PRP, conditioned by the age of the donors, affects the magnitude of the biological response.

scholarly journals Design and In Vitro Study of a Dual Drug-Loaded Delivery System Produced by Electrospinning for the Treatment of Acute Injuries of the Central Nervous System

Pharmaceutics ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 848
Author(s):  
Luisa Stella Dolci ◽  
Rosaria Carmela Perone ◽  
Roberto Di Gesù ◽  
Mallesh Kurakula ◽  
Chiara Gualandi ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Delivery System ◽  
Synergistic Effects ◽  
In Vitro Release ◽  
Health Priorities ◽  
The Central Nervous System ◽  
Vitro Release ◽  
Dual Drug

Vascular and traumatic injuries of the central nervous system are recognized as global health priorities. A polypharmacology approach that is able to simultaneously target several injury factors by the combination of agents having synergistic effects appears to be promising. Herein, we designed a polymeric delivery system loaded with two drugs, ibuprofen (Ibu) and thyroid hormone triiodothyronine (T3) to in vitro release the suitable amount of the anti-inflammation and the remyelination drug. As a production method, electrospinning technology was used. First, Ibu-loaded micro (diameter circa 0.95–1.20 µm) and nano (diameter circa 0.70 µm) fibers were produced using poly(l-lactide) PLLA and PLGA with different lactide/glycolide ratios (50:50, 75:25, and 85:15) to select the most suitable polymer and fiber diameter. Based on the in vitro release results and in-house knowledge, PLLA nanofibers (mean diameter = 580 ± 120 nm) loaded with both Ibu and T3 were then successfully produced by a co-axial electrospinning technique. The in vitro release studies demonstrated that the final Ibu/T3 PLLA system extended the release of both drugs for 14 days, providing the target sustained release. Finally, studies in cell cultures (RAW macrophages and neural stem cell-derived oligodendrocyte precursor cells—OPCs) demonstrated the anti-inflammatory and promyelinating efficacy of the dual drug-loaded delivery platform.

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