scholarly journals Nano-in-Micro-Particles Consisting of PLGA Nanoparticles Embedded in Chitosan Microparticles via Spray-Drying Enhances Their Uptake in the Olfactory Mucosa

2021 ◽  
Vol 12 ◽  
Author(s):  
Lena Marie Spindler ◽  
Andreas Feuerhake ◽  
Simone Ladel ◽  
Cemre Günday ◽  
Johannes Flamm ◽  
...  

Intranasal delivery has gained prominence since 1990, when the olfactory mucosa was recognized as the window to the brain and the central nervous system (CNS); this has enabled the direct site specific targeting of neurological diseases for the first time. Intranasal delivery is a promising route because general limitations, such as the blood-brain barrier (BBB) are circumvented. In the treatment of multiple sclerosis (MS) or Alzheimer’s disease, for example, future treatment prospects include specialized particles as delivery vehicles. Poly(lactic-co-glycolic acid) (PLGA) nanoparticles are well known as promising delivery systems, especially in the area of nose-to-brain (N2B) delivery. Chitosan is also broadly known as a functional additive due to its ability to open tight junctions. In this study, we produced PLGA nanoparticles of different sizes and revealed for the first time their size-time-dependent uptake mechanism into the lamina propria of porcine olfactory mucosa. The intracellular uptake was observed for 80 and 175 nm within only 5 min after application to the epithelium. After 15 min, even 520 nm particles were detected, associated with nuclei. Especially the presence of only 520 nm particles in neuronal fibers is remarkable, implying transcellular and intracellular transport via the olfactory or the trigeminal nerve to the brain and the CNS. Additionally, we developed successfully specialized Nano-in-Micro particles (NiMPs) for the first time via spray drying, consisting of PLGA nanoparticles embedded into chitosan microparticles, characterized by high encapsulation efficiencies up to 51%, reproducible and uniform size distribution, as well as smooth surface. Application of NiMPs accelerated the uptake compared to purely applied PLGA nanoparticles. NiMPs were spread over the whole transverse section of the olfactory mucosa within 15 min. Faster uptake is attributed to additional paracellular transport, which was examined via tight-junction-opening. Furthermore, a separate chitosan penetration gradient of ∼150 µm caused by dissociation from PLGA nanoparticles was observed within 15 min in the lamina propria, which was demonstrated to be proportional to an immunoreactivity gradient of CD14. Due to the beneficial properties of the utilized chitosan-derivative, regarding molecular weight (150–300 kDa), degree of deacetylation (80%), and particle size (0.1–10 µm) we concluded that M2-macrophages herein initiated an anti-inflammatory reaction, which seems to already take place within 15 min following chitosan particle application. In conclusion, we demonstrated the possibility for PLGA nanoparticles, as well as for chitosan NiMPs, to take all three prominent intranasal delivery pathways to the brain and the CNS; namely transcellular, intracellular via neuronal cells, and paracellular transport.

2016 ◽  
Vol Volume 11 ◽  
pp. 6547-6559 ◽  
Author(s):  
Chenchen Bi ◽  
Aiping Wang ◽  
Yongchao Chu ◽  
Sha Liu ◽  
Hongjie Mu ◽  
...  

2021 ◽  
pp. 1-10
Author(s):  
Shahul Mujib Kamal ◽  
Norazryana Mat Dawi ◽  
Hamidreza Namazi

BACKGROUND: Walking like many other actions of a human is controlled by the brain through the nervous system. In fact, if a problem occurs in our brain, we cannot walk correctly. Therefore, the analysis of the coupling of brain activity and walking is very important especially in rehabilitation science. The complexity of movement paths is one of the factors that affect human walking. For instance, if we walk on a path that is more complex, our brain activity increases to adjust our movements. OBJECTIVE: This study for the first time analyzed the coupling of walking paths and brain reaction from the information point of view. METHODS: We analyzed the Shannon entropy for electroencephalography (EEG) signals versus the walking paths in order to relate their information contents. RESULTS: According to the results, walking on a path that contains more information causes more information in EEG signals. A strong correlation (p= 0.9999) was observed between the information contents of EEG signals and walking paths. Our method of analysis can also be used to investigate the relation among other physiological signals of a human and walking paths, which has great benefits in rehabilitation science.


2004 ◽  
Vol 380 (3) ◽  
pp. 749-756 ◽  
Author(s):  
Yong-Xin SUN ◽  
Kazuhito TSUBOI ◽  
Yasuo OKAMOTO ◽  
Takeharu TONAI ◽  
Makoto MURAKAMI ◽  
...  

Anandamide (an endocannabinoid) and other bioactive long-chain NAEs (N-acylethanolamines) are formed by direct release from N-acyl-PE (N-acyl-phosphatidylethanolamine) by a PLD (phospholipase D). However, the possible presence of a two-step pathway from N-acyl-PE has also been suggested previously, which comprises (1) the hydrolysis of N-acyl-PE to N-acyl-lysoPE by PLA1/PLA2 enzyme(s) and (2) the release of NAEs from N-acyllysoPE by lysoPLD (lysophospholipase D) enzyme(s). In the present study we report for the first time the characterization of enzymes responsible for this pathway. The PLA1/PLA2 activity for N-palmitoyl-PE was found in various rat tissues, with the highest activity in the stomach. This stomach enzyme was identified as group IB sPLA2 (secretory PLA2), and its product was determined as N-acyl-1-acyl-lysoPE. Recombinant group IB, IIA and V of sPLA2s were also active with N-palmitoyl-PE, whereas group X sPLA2 and cytosolic PLA2α were inactive. In addition, we found wide distribution of lysoPLD activity generating N-palmitoylethanolamine from N-palmitoyl-lysoPE in rat tissues, with higher activities in the brain and testis. Based on several lines of enzymological evidence, the lysoPLD enzyme could be distinct from the known N-acyl-PE-hydrolysing PLD. sPLA2-IB dose dependently enhanced the production of N-palmitoylethanolamine from N-palmitoyl-PE in the brain homogenate showing the lysoPLD activity. N-Arachidonoyl-PE and N-arachidonoyl-lysoPE as anandamide precursors were also good substrates of sPLA2-IB and the lysoPLD respectively. These results suggest that the sequential actions of PLA2 and lysoPLD may constitute another biosynthetic pathway for NAEs, including anandamide.


Parasitology ◽  
1996 ◽  
Vol 113 (6) ◽  
pp. 559-565 ◽  
Author(s):  
M. K. S. Gustafsson ◽  
A. M. Lindholm ◽  
N. B. Terenina ◽  
M. Reuter

SUMMARYThe free radical nitric oxide (NO), which is synthesized by nitric oxide synthase (NOS), has recently been discovered to function as a neuronal messenger. The presence of NOS was detected in the nervous system of adult Hymenolepis diminuta with NADPH-diaphorase (NADPH-d) histochemistry. The NADPH-d histochemical reaction is regarded as a selective marker for NOS in neuronal tissue. NADPH-d staining was observed in nerve fibres in the main and minor nerve cords and the transverse ring commissures, and in cell bodies in the brain commissure, along the main nerve cords, in the suckers and the rostellar sac. NADPH-d staining was also observed in the wall of the internal seminal vesicle and the genital atrium. The pattern of NADPH-d staining was compared with that of the 5-HT immunoreactive nervous elements. The NADPH-d staining reaction and the 5-HT immunoreactivity occur in separate sets of neurons. This is the first time the NADPH-d reaction has been demonstrated in the nervous system of a flatworm, indicating that NOS is present and that NO can be produced at this level of evolution.


2009 ◽  
Vol 24 (S1) ◽  
pp. 1-1
Author(s):  
M. Stankovic ◽  
S. Vucetic-Arsic ◽  
S. Alcaz ◽  
J. Cvejic

Aim:We want to present a polymorphic clinical features like: hallutinations, paranoid ideas, agitation and violence as a result of prolonged cocaine intranasal consumption.Methods:We exposed a 30-year old male patient with ICD-X diagnostic criteria for cocaine dependence (intranasal consumption) that treated in the outpatient unit of Special Hospital of Addicitons, Belgrade, Serbia from April to July 2008. We used the medical records, psychical examination, psychiatric interwievs, standard blood sampling and cocaine urine detections sample (positive).Results:Observations a specific and polymorphic clinical features with presence of psychotic symptoms after cocaine consumptions in our male patient, for the first time after 5 years of cocaine dependence: auditory hallucinations (two- voice speakers), paranoid persecution ideas and suspiciousness, agitation with appearance of vegetative symptomatology (palpitations, sweating, pupil dilatation), extremely violence behavior to other people, complete social reductions (“armed to the outside world”, refused any personal contact and isolated from friends and family, permanent outdoor checking). There was an intensive fear too and impaired judgment.Conclusions:Permanent cocaine consumption can result with produce a numerous of psychiatric symptoms and syndromes as our experience does. It is similar to the findings of other studies and papers reviewed. It is suppose that cocaine has numerous effects on important neurotransmitters in the brain, such as increase as well as the release of dopamine and it related with aggressiveness, hallucinations and other psychiatric symptoms.


2021 ◽  
pp. 1-11
Author(s):  
Najmeh Pakniyat ◽  
Mohammad Hossein Babini ◽  
Vladimir V. Kulish ◽  
Hamidreza Namazi

BACKGROUND: Analysis of the heart activity is one of the important areas of research in biomedical science and engineering. For this purpose, scientists analyze the activity of the heart in various conditions. Since the brain controls the heart’s activity, a relationship should exist among their activities. OBJECTIVE: In this research, for the first time the coupling between heart and brain activities was analyzed by information-based analysis. METHODS: Considering Shannon entropy as the indicator of the information of a system, we recorded electroencephalogram (EEG) and electrocardiogram (ECG) signals of 13 participants (7 M, 6 F, 18–22 years old) in different external stimulations (using pineapple, banana, vanilla, and lemon flavors as olfactory stimuli) and evaluated how the information of EEG signals and R-R time series (as heart rate variability (HRV)) are linked. RESULTS: The results indicate that the changes in the information of the R-R time series and EEG signals are strongly correlated (ρ=-0.9566). CONCLUSION: We conclude that heart and brain activities are related.


2021 ◽  
Author(s):  
Felipe Lemos ◽  
Caio Prins ◽  
Raul Carpi-Santos ◽  
Ingrid Waclawiak ◽  
Sofia Santos ◽  
...  

Abstract Galectin-3 stabilizes cell-cell junctions and regulates inflammatory pathways in the gut-liver axis. Galectin-3 knockout (Lgals3−/−) mice have atypical behaviors by obscure mechanisms. Given that BALB/c mice naturally develop low-sociability, stereotypies and restrict interest, they have been included as autism experimental model. Our major aims were to investigate whether galectin-3 in the gut-liver axis interferes with autistic-like behaviors analyzing BALB/c Lgals3−/− mice or under partial inhibition of galectin-3 oral intake of cow’s milk for 7 days. Behavioral patterns were assessed using a three-chambers test, open field, and self-grooming. Histological analysis and immunohistochemistry (Galectin-3, NOS-2, Iba-1, Ki-67, Dll-4, Shank-3, Synaptophysin and Drebrin) were performed in gut, liver, and/or brain. Lgals3−/− mice amplified stereotypies, social retraction and restrict interest associated with reduction of cerebral Shank-3+ cells. In Lgals3+/+ mice, cow’s milk intake also amplified atypical behaviors, reduced galectin-3 in enterocytes and Kupffer cells, and disturbed niches of intestinal KI67+ and Dll-4+ cells and hepatic NOS2+ cells. In the brain of milk-treated mice, Iba-1+ microglial cells and NOS2+ Purkinje cells were increased whereas Shank-3+ and Drebrin+Synaptophysin+ cells were reduced suggesting, for the first time, that galectin-3 interferes with autistic behavior. Perhaps, a perspective to new therapies in genetically predisposed individuals to atypical behaviors.


Author(s):  
Vaibhav Walia ◽  
Munish Garg

Fritz Heinrich Lewy described the intracytoplasmic inclusions found in the neurons for the very first time. In 1919 these inclusions were termed as “LBs” by Tretiakoff. LBs were found in the brain of the patients suffering from Lewy body disease (LBD). LBD is characterized by the presence of Parkinsonian symptoms in the earlier stages and dementia in the later stages of the disease. LBs were classified on the basis of the region of the brain in which they are distributed and so is the case of the LBD means the type of the LBD depends on the anatomical areas of the brain involved. LBD is not a single disorder. It is a spectrum of disorders. This chapter addresses the entire profile of LBs, types, composition, formation, and various LB pathologies as well as diagnostic criteria and pharmacotherapy.


2020 ◽  
pp. 58-81
Author(s):  
John Parrington

Visual light, and radiation of other frequencies, are highly important for scientific research. The first light microscopes made it possible for the first time to see that organisms from plants to humans are composed of cells. Electron microscopes have allowed scientists to study the structural components of cells in great detail, and even determine the shapes of individual proteins. Many lifeforms also use light to attract a mate or prey, or deter an attacker. Following the identification of the gene coding for the fluorescent protein that makes certain jellyfish glow green it has become possible to use this to genetically label proteins in a living cell, or even a live animal. This means that now the location of proteins in a cell can be determined exactly. A major recent step forward in neuroscience came with the discovery of protein channels in algae that conduct ions in response to light. By creating transgenic mice that have these proteins in their brain neurons, it is now possible to modulate the activity of these neurons by shining light into the brain though microscopic fibre optic cables. This new science of optogenetics allows neurons to be switched on or off experimentally. The optogenetic approach has been used to uncover the neural circuits involved in memory, pain and pleasure. In the future this technique might be used to treat physical pain or depression in people. Controversially, it might be also be misused, to supress memories, or even create completely false ones in people’s heads.


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