scholarly journals Establishment of an Olfactory Region-specific Intranasal Delivery Technique in Mice to Target the Central Nervous System

2022 ◽  
Vol 12 ◽  
Author(s):  
Johannes Flamm ◽  
Sunniva Hartung ◽  
Stella Gänger ◽  
Frank Maigler ◽  
Claudia Pitzer ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Ct Scan ◽  
Systemic Circulation ◽  
Intranasal Delivery ◽  
Step Procedure ◽  
Delivery Technique ◽  
Neuronal Connections ◽  
The Central Nervous System ◽  
Cns Delivery

We have recently developed a region-specific catheter-based intranasal application method in mice by using CT scan-based 3D cast models of the murine nose (DOI: 10.2376/0005-9366-17,102). This technique is able to specifically deliver drugs to the olfactory region or to the respiratory region only. Thereby, intranasally administered drugs could be delivered either via neuronal connections to the central nervous system or via the well-perfused rostral parts of the nasal mucosa to the systemic circulation. In the present study, we transferred successfully this novel delivery technique to C57Bl/6 mice and determined parameters such as insertions depth of the catheter and maximum delivery volume in dependence to the weight of the mouse. Breathing was simulated to verify that the volume remains at the targeted area. A step-by-step procedure including a video is presented to adopt this technique for standardized and reproducible intranasal central nervous system (CNS) delivery studies (DOI: 10.3390/pharmaceutics13111904).

scholarly journals The Route by Which Intranasally Delivered Stem Cells Enter the Central Nervous System

2018 ◽  
Vol 27 (3) ◽  
pp. 501-514 ◽  
Author(s):  
Carlos Galeano ◽  
Zhifang Qiu ◽  
Anuja Mishra ◽  
Steven L. Farnsworth ◽  
Jacob J. Hemmi ◽  
...  
Keyword(s):  
Stem Cells ◽  
Central Nervous System ◽  
Nervous System ◽  
Nasal Cavity ◽  
Olfactory Epithelium ◽  
Cribriform Plate ◽  
Intranasal Delivery ◽  
Immunodeficient Mice ◽  
Stem Cell Delivery ◽  
The Central Nervous System

Intranasal administration is a promising route of delivery of stem cells to the central nervous system (CNS). Reports on this mode of stem cell delivery have not yet focused on the route across the cribriform plate by which cells move from the nasal cavity into the CNS. In the current experiments, human mesenchymal stem cells (MSCs) were isolated from Wharton’s jelly of umbilical cords and were labeled with extremely bright quantum dots (QDs) in order to track the cells efficiently. At 2 h after intranasal delivery in immunodeficient mice, the labeled cells were found under the olfactory epithelium, crossing the cribriform plate adjacent to the fila olfactoria, and associated with the meninges of the olfactory bulb. At all times, the cells were separate from actual nerve tracts; this location is consistent with them being in the subarachnoid space (SAS) and its extensions through the cribriform plate into the nasal mucosa. In their location under the olfactory epithelium, they appear to be within an expansion of a potential space adjacent to the turbinate bone periosteum. Therefore, intranasally administered stem cells appear to cross the olfactory epithelium, enter a space adjacent to the periosteum of the turbinate bones, and then enter the SAS via its extensions adjacent to the fila olfactoria as they cross the cribriform plate. These observations should enhance understanding of the mode by which stem cells can reach the CNS from the nasal cavity and may guide future experiments on making intranasal delivery of stem cells efficient and reproducible.

scholarly journals Recent Developments in Microfluidic Technologies for Central Nervous System Targeted Studies

Pharmaceutics ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 542
Author(s):  
Maria Inês Teixeira ◽  
Maria Helena Amaral ◽  
Paulo C. Costa ◽  
Carla M. Lopes ◽  
Dimitrios A. Lamprou
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
State Of The Art ◽  
Physicochemical Characteristics ◽  
Future Perspectives ◽  
Invaluable Tool ◽  
Recent Developments ◽  
The Central Nervous System ◽  
Cns Delivery ◽  
Reproducible Manner

Neurodegenerative diseases (NDs) bear a lot of weight in public health. By studying the properties of the blood-brain barrier (BBB) and its fundamental interactions with the central nervous system (CNS), it is possible to improve the understanding of the pathological mechanisms behind these disorders and create new and better strategies to improve bioavailability and therapeutic efficiency, such as nanocarriers. Microfluidics is an intersectional field with many applications. Microfluidic systems can be an invaluable tool to accurately simulate the BBB microenvironment, as well as develop, in a reproducible manner, drug delivery systems with well-defined physicochemical characteristics. This review provides an overview of the most recent advances on microfluidic devices for CNS-targeted studies. Firstly, the importance of the BBB will be addressed, and different experimental BBB models will be briefly discussed. Subsequently, microfluidic-integrated BBB models (BBB/brain-on-a-chip) are introduced and the state of the art reviewed, with special emphasis on their use to study NDs. Additionally, the microfluidic preparation of nanocarriers and other compounds for CNS delivery has been covered. The last section focuses on current challenges and future perspectives of microfluidic experimentation.

p-Toluenesulphonic Acid as a Fixative

1962 ◽  
Vol s3-103 (62) ◽  
pp. 163-171
Author(s):  
MIGNON MALM
Keyword(s):  
Aqueous Solution ◽  
Central Nervous System ◽  
Nervous System ◽  
Blood Vessels ◽  
Saline Solution ◽  
Histological Techniques ◽  
Step Procedure ◽  
The Central Nervous System ◽  
Test Objects ◽  
Cellular Shrinkage

p-toluenesulphonic acid in aqueous solution is introduced to histologists and recommended for fixation of the central nervous system by a three-step procedure: flushing the blood-vessels with a saline solution, filling the vessels with the fixative, and delaying the autopsy. With rats and guinea-pigs as test objects, a solution of at least 0.5 M gave excellent results, as evidenced by the minimum of cellular shrinkage, the absence of perivascular and perineuronal spaces, and the clarity of cellular membranes and basiphil material. The neurones, neuroglia, microglia, and blood-vessels were well defined when stained by conventional histological techniques. Cytological details became more prominent because the tissue had shrunk less than in routine preparations. The acid is non-volatile, colourless, pleasant to handle, and low in price.

scholarly journals Neuropeptide Localization in Lymnaea stagnalis: From the Central Nervous System to Subcellular Compartments

2021 ◽  
Vol 14 ◽  
Author(s):  
Ellen A. Wood ◽  
Sylwia A. Stopka ◽  
Linwen Zhang ◽  
Sara Mattson ◽  
Gabor Maasz ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Lymnaea Stagnalis ◽  
Single Cell Analysis ◽  
Model Organism ◽  
Pond Snail ◽  
Ms Imaging ◽  
Subcellular Compartments ◽  
Neuronal Connections ◽  
The Central Nervous System

Due to the relatively small number of neurons (few tens of thousands), the well-established multipurpose model organism Lymnaea stagnalis, great pond snail, has been extensively used to study the functioning of the nervous system. Unlike the more complex brains of higher organisms, L. stagnalis has a relatively simple central nervous system (CNS) with well-defined circuits (e.g., feeding, locomotion, learning, and memory) and identified individual neurons (e.g., cerebral giant cell, CGC), which generate behavioral patterns. Accumulating information from electrophysiological experiments maps the network of neuronal connections and the neuronal circuits responsible for basic life functions. Chemical signaling between synaptic-coupled neurons is underpinned by neurotransmitters and neuropeptides. This review looks at the rapidly expanding contributions of mass spectrometry (MS) to neuropeptide discovery and identification at different granularity of CNS organization. Abundances and distributions of neuropeptides in the whole CNS, eleven interconnected ganglia, neuronal clusters, single neurons, and subcellular compartments are captured by MS imaging and single cell analysis techniques. Combining neuropeptide expression and electrophysiological data, and aided by genomic and transcriptomic information, the molecular basis of CNS-controlled biological functions is increasingly revealed.

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