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Rahman, Faiz Ur, You-Rim Kim, Eun-Kyeung Kim, Hae-rim Kim, Sang-Mi Cho, Chin-Soo Lee, Su Jin Kim i in. "Topoisomerase IIIβ Deficiency Induces Neuro-Behavioral Changes and Brain Connectivity Alterations in Mice". International Journal of Molecular Sciences 22, nr 23 (26.11.2021): 12806. http://dx.doi.org/10.3390/ijms222312806.
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Topoisomerase IIIβ (Top3β), the only dual-activity topoisomerase in mammals that can change topology of both DNA and RNA, is known to be associated with neurodevelopment and mental dysfunction in humans. However, there is no report showing clear associations of Top3β with neuropsychiatric phenotypes in mice. Here, we investigated the effect of Top3β on neuro-behavior using newly generated Top3β deficient (Top3β−/−) mice. We found that Top3β−/− mice showed decreased anxiety and depression-like behaviors. The lack of Top3β was also associated with changes in circadian rhythm. In addition, a clear expression of Top3β was demonstrated in the central nervous system of mice. Positron emission tomography/computed tomography (PET/CT) analysis revealed significantly altered connectivity between many brain regions in Top3β−/− mice, including the connectivity between the olfactory bulb and the cerebellum, the connectivity between the amygdala and the olfactory bulb, and the connectivity between the globus pallidus and the optic nerve. These connectivity alterations in brain regions are known to be linked to neurodevelopmental as well as psychiatric and behavioral disorders in humans. Therefore, we conclude that Top3β is essential for normal brain function and behavior in mice and that Top3β could be an interesting target to study neuropsychiatric disorders in humans.
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Germanese, Danila, Sara Colantonio, Mario D’Acunto, Veronica Romagnoli, Antonio Salvati i Maurizia Brunetto. "An E-Nose for the Monitoring of Severe Liver Impairment: A Preliminary Study". Sensors 19, nr 17 (22.08.2019): 3656. http://dx.doi.org/10.3390/s19173656.
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Biologically inspired to mammalian olfactory system, electronic noses became popular during the last three decades. In literature, as well as in daily practice, a wide range of applications are reported. Nevertheless, the most pioneering one has been (and still is) the assessment of the human breath composition. In this study, we used a prototype of electronic nose, called Wize Sniffer (WS) and based it on an array of semiconductor gas sensor, to detect ammonia in the breath of patients suffering from severe liver impairment. In the setting of severely impaired liver, toxic substances, such as ammonia, accumulate in the systemic circulation and in the brain. This may result in Hepatic Encephalopathy (HE), a spectrum of neuro–psychiatric abnormalities which include changes in cognitive functions, consciousness, and behaviour. HE can be detected only by specific but time-consuming and burdensome examinations, such as blood ammonia levels assessment and neuro-psychological tests. In the presented proof-of-concept study, we aimed at investigating the possibility of discriminating the severity degree of liver impairment on the basis of the detected breath ammonia, in view of the detection of HE at its early stage.
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Moscavitch, Samuel-Datum, Martine Szyper-Kravitz i Yehuda Shoenfeld. "Autoimmune pathology accounts for common manifestations in a wide range of neuro-psychiatric disorders: The olfactory and immune system interrelationship". Clinical Immunology 130, nr 3 (marzec 2009): 235–43. http://dx.doi.org/10.1016/j.clim.2008.10.010.
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Sodagar, Aisha, Rasab Javed, Hira Tahir, Saiful Izwan Abd Razak, Muhammad Shakir, Muhammad Naeem, Abdul Halim Abdul Yusof i in. "Pathological Features and Neuroinflammatory Mechanisms of SARS-CoV-2 in the Brain and Potential Therapeutic Approaches". Biomolecules 12, nr 7 (11.07.2022): 971. http://dx.doi.org/10.3390/biom12070971.
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The number of deaths has been increased due to COVID-19 infections and uncertain neurological complications associated with the central nervous system. Post-infections and neurological manifestations in neuronal tissues caused by COVID-19 are still unknown and there is a need to explore how brainstorming promoted congenital impairment, dementia, and Alzheimer’s disease. SARS-CoV-2 neuro-invasion studies in vivo are still rare, despite the fact that other beta-coronaviruses have shown similar properties. Neural (olfactory or vagal) and hematogenous (crossing the blood–brain barrier) pathways have been hypothesized in light of new evidence showing the existence of SARS-CoV-2 host cell entry receptors into the specific components of human nerve and vascular tissue. Spike proteins are the primary key and structural component of the COVID-19 that promotes the infection into brain cells. Neurological manifestations and serious neurodegeneration occur through the binding of spike proteins to ACE2 receptor. The emerging evidence reported that, due to the high rate in the immediate wake of viral infection, the olfactory bulb, thalamus, and brain stem are intensely infected through a trans-synaptic transfer of the virus. It also instructs the release of chemokines, cytokines, and inflammatory signals immensely to the blood–brain barrier and infects the astrocytes, which causes neuroinflammation and neuron death; and this induction of excessive inflammation and immune response developed in more neurodegeneration complications. The present review revealed the pathophysiological effects, molecular, and cellular mechanisms of possible entry routes into the brain, pathogenicity of autoantibodies and emerging immunotherapies against COVID-19.
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Kozlov, P. V. "Regulation of female sexual behavior and possibilities of drug therapy". Meditsinskiy sovet = Medical Council, nr 5 (18.04.2023): 15–20. http://dx.doi.org/10.21518/ms2023-063.
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Female sexual behavior is under the complex influence of psycho-emotional, neuroendocrine and social factors. The realization of normal sexual activity in women is possible if many conditions are met and, first of all, ensuring a positive psycho-emotional background, safety, a satisfactory state of health, as well as comfortable interpersonal relationships for most women. In addition to significant psychological and social impact, accumulated modern scientific data confirm the important role of neuro-hormonal regulation of sexual behavior and suggest the potential effectiveness of pharmacological therapy. Unfortunately, however, medical strategies for correcting female sexual disorders are limited. Currently, in some countries, several drugs that increase female sexual activity are allowed for use, however, all of them are not registered and are not approved for use on the territory of the Russian Federation. The article briefly describes the neural mechanisms of the main areas of the central nervous system underlying receptivity and sexual attraction, namely the olfactory and limbic systems, the neocortex. The main attention is paid to the function of neurotransmitters and hormones that are critically involved in the modulation of emotions and sexual behavior, including the inhibitory mediator of gamma aminobutyric acid (GABA), estrogens, testosterone, and the excitatory mediator glutamate. The stages of development, the results of experimental and clinical studies to assess the effectiveness and safety of the unique Russian neuropeptide drug Desirex, which is a stimulant of sexual behavior due to the mechanism of reversible suppression of the GABAergic system, nonspecific stimulation of the dopaminergic system of motivation and reinforcement of positive emotions and disinhibition of the controlling function of the neocortex, are presented in detail.
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Blits, Bas, Gerard J. Boer i Joost Verhaagen. "Pharmacological, Cell, and Gene Therapy Strategies to Promote Spinal Cord Regeneration". Cell Transplantation 11, nr 6 (wrzesień 2002): 593–613. http://dx.doi.org/10.3727/000000002783985521.
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In this review, recent studies using pharmacological treatment, cell transplantation, and gene therapy to promote regeneration of the injured spinal cord in animal models will be summarized. Pharmacological and cell transplantation treatments generally revealed some degree of effect on the regeneration of the injured ascending and descending tracts, but further improvements to achieve a more significant functional recovery are necessary. The use of gene therapy to promote repair of the injured nervous system is a relatively new concept. It is based on the development of methods for delivering therapeutic genes to neurons, glia cells, or nonneural cells. Direct in vivo gene transfer or gene transfer in combination with (neuro)transplantation (ex vivo gene transfer) appeared powerful strategies to promote neuronal survival and axonal regrowth following traumatic injury to the central nervous system. Recent advances in understanding the cellular and molecular mechanisms that govern neuronal survival and neurite outgrowth have enabled the design of experiments aimed at viral vector-mediated transfer of genes encoding neurotrophic factors, growth-associated proteins, cell adhesion molecules, and antiapoptotic genes. Central to the success of these approaches was the development of efficient, nontoxic vectors for gene delivery and the acquirement of the appropriate (genetically modified) cells for neurotransplantation. Direct gene transfer in the nervous system was first achieved with herpes viral and E1-deleted adenoviral vectors. Both vector systems are problematic in that these vectors elicit immunogenic and cytotoxic responses. Adeno-associated viral vectors and lentiviral vectors constitute improved gene delivery systems and are beginning to be applied in neuroregeneration research of the spinal cord. Ex vivo approaches were initially based on the implantation of genetically modified fibroblasts. More recently, transduced Schwann cells, genetically modified pieces of peripheral nerve, and olfactory ensheathing glia have been used as implants into the injured spinal cord.
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Montegiove, Nicolò, Eleonora Calzoni, Carla Emiliani i Alessio Cesaretti. "Biopolymer Nanoparticles for Nose-to-Brain Drug Delivery: A New Promising Approach for the Treatment of Neurological Diseases". Journal of Functional Biomaterials 13, nr 3 (24.08.2022): 125. http://dx.doi.org/10.3390/jfb13030125.
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Diseases affecting the central nervous system (CNS) are among the most disabling and the most difficult to cure due to the presence of the blood–brain barrier (BBB) which represents an impediment from a therapeutic and diagnostic point of view as it limits the entry of most drugs. The use of biocompatible polymer nanoparticles (NPs) as vehicles for targeted drug delivery to the brain arouses increasing interest. However, the route of administration of these vectors remains critical as the drug must be delivered without being degraded to achieve a therapeutic effect. An innovative approach for the administration of drugs to the brain using polymeric carriers is represented by the nose-to-brain (NtB) route which involves the administration of the therapeutic molecule through the neuro-olfactory epithelium of the nasal mucosa. Nasal administration is a non-invasive approach that allows the rapid transport of the drug directly to the brain and minimizes its systemic exposure. To date, many studies involve the use of polymer NPs for the NtB transport of drugs to the brain for the treatment of a whole series of disabling neurological diseases for which, as of today, there is no cure. In this review, various types of biodegradable polymer NPs for drug delivery to the brain through the NtB route are discussed and particular attention is devoted to the treatment of neurological diseases such as Glioblastoma and neurodegenerative diseases.
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Uchida, Naoshige, Cindy Poo i Rafi Haddad. "Coding and Transformations in the Olfactory System". Annual Review of Neuroscience 37, nr 1 (8.07.2014): 363–85. http://dx.doi.org/10.1146/annurev-neuro-071013-013941.
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Friedrich, Rainer W. "Neuronal Computations in the Olfactory System of Zebrafish". Annual Review of Neuroscience 36, nr 1 (8.07.2013): 383–402. http://dx.doi.org/10.1146/annurev-neuro-062111-150504.
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Holy, Timothy E. "The Accessory Olfactory System: Innately Specialized or Microcosm of Mammalian Circuitry?" Annual Review of Neuroscience 41, nr 1 (8.07.2018): 501–25. http://dx.doi.org/10.1146/annurev-neuro-080317-061916.
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In mammals, the accessory olfactory system is a distinct circuit that has received attention for its role in detecting and responding to pheromones. While the neuroscientific investigation of this system is comparatively new, recent advances and its compact size have made it an attractive model for developing an end-to-end understanding of such questions as regulation of essential behaviors, plasticity, and individual recognition. Recent discoveries have indicated a need to reevaluate our conception of this system, suggesting that ( a) physical principles—rather than biological necessity—play an underappreciated role in its raison d'être and that ( b) the anatomy of downstream projections is not dominated by unique specializations but instead consists of an abbreviated cortical/basal ganglia motif reminiscent of other sensorimotor systems. These observations suggest that the accessory olfactory system distinguishes itself primarily by the physicochemical properties of its ligands, but its architecture is otherwise a microcosm of mammalian neurocircuitry.
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Usende, I. L. "Investigation of some aspects of the Neuro-Morphometry of the African catfish (Clarias gariepinus)". Journal of Veterinary and Biomedical Sciences 2, nr 2 (1.12.2020): 19–29. http://dx.doi.org/10.36108/jvbs/9102.20.0230.
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The brain is one of the most important organs, as it controls numerous bodily functions. Due to its crucial regulatory roles, the nervous system of fishes and especially the brain needs more research. Catfish (order Siluriformes or Nematognathi) are ray finned fish, named for their prominent whiskers (barbels), which resembles the whisker of a cat. The Nigerian cultured catfish (Clarias gariepinus) have small eyes and wide mouths, which suggest low dependence on vision, nocturnal activity, and predatory habits. Herein, we describe the gross morphology and morphometrics of the brain of Clarias gariepinus. Five apparently healthy adult catfish (Clarias gariepinus) without sex differences were used. Cranial nerves and spinal cord were severed as the brain case was removed, after which all the morphological descriptions were done. Ten morphometric parameters were also measured. The generated data were graphically illustrated with scatterplot and biplot, as well; the regression analysis showing the stepwise fit for the prediction of the brain weight from other measured parameters was also presented. The olfactory bulb is large, somewhat rounded and rostral. The cerebellumin all examined brain was the largest structure of the brain with a cerebellar length and width of 1.16±0.11 cm and 0.82±0.03, respectively. The optic tectum, lobusvagi, lobusfacialis and eminentiagranularis were also well developed but small in size. Although, the behavior of the catfish (Clarias gariepinus) is still unknown, the relative proportion of the cerebellum, optic tectum, eminentiagranularis, lobusfacialis and lobusvagi, might be related to carnivory and an enhanced capacity for food selection in this species. In conclusion, the report herein has helped to provide useful information for the first time on morphology of the brains of Clarias gariepinus cultured in Nigeria, for understanding of the neurobehaviour and habits of this species.
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Portela-Lomba, María, Diana Simón, David Fernández de Sevilla, Mª Teresa Moreno-Flores i Javier Sierra. "Small molecules fail to induce direct reprogramming of adult rat olfactory ensheathing glia to mature neurons". Frontiers in Molecular Neuroscience 16 (24.02.2023). http://dx.doi.org/10.3389/fnmol.2023.1110356.
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An approach to generate new neurons after central nervous system injury or disease is direct reprogramming of the individual's own somatic cells into differentiated neurons. This can be achieved either by transduction of viral vectors that express neurogenic transcription factors and/or through induction with small molecules, avoiding introducing foreign genetic material in target cells. In this work, we propose olfactory ensheathing glia (OEG) as a candidate for direct reprogramming to neurons with small molecules due to its well-characterized neuro-regenerative capacity. After screening different combinations of small molecules in different culture conditions, only partial reprogramming was achieved: induced cells expressed neuronal markers but lacked the ability of firing action potentials. Our work demonstrates that direct conversion of adult olfactory ensheathing glia to mature, functional neurons cannot be induced only with pharmacological tools.
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Jiao, Li, Yun Yang, Wenhai Yu, Yuan Zhao, Haiting Long, Jiahong Gao, Kaiyun Ding i in. "The olfactory route is a potential way for SARS-CoV-2 to invade the central nervous system of rhesus monkeys". Signal Transduction and Targeted Therapy 6, nr 1 (24.04.2021). http://dx.doi.org/10.1038/s41392-021-00591-7.
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AbstractNeurological manifestations are frequently reported in the COVID-19 patients. Neuromechanism of SARS-CoV-2 remains to be elucidated. In this study, we explored the mechanisms of SARS-CoV-2 neurotropism via our established non-human primate model of COVID-19. In rhesus monkey, SARS-CoV-2 invades the CNS primarily via the olfactory bulb. Thereafter, viruses rapidly spread to functional areas of the central nervous system, such as hippocampus, thalamus, and medulla oblongata. The infection of SARS-CoV-2 induces the inflammation possibly by targeting neurons, microglia, and astrocytes in the CNS. Consistently, SARS-CoV-2 infects neuro-derived SK-N-SH, glial-derived U251, and brain microvascular endothelial cells in vitro. To our knowledge, this is the first experimental evidence of SARS-CoV-2 neuroinvasion in the NHP model, which provides important insights into the CNS-related pathogenesis of SARS-CoV-2.
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Huertas, Mar, i Maruf Mohammad Billah. "Pathogen odors elicit distinct neurosteroid and behavioral responses in Rainbow trout (Oncorhynchus mykiss)". Physiology 38, S1 (maj 2023). http://dx.doi.org/10.1152/physiol.2023.38.s1.5795814.
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Rainbow trout can smell virus and bacteria cues that in turn activate an immune response in the brain in absence of a systemic response (i.e. the immune response is activated by the nervous system instead of the pathogen inside tissues or bloodstream). However, little is known if pathogen odors can elicit different physiological responses (i.e. behavioral and immune) and how are pathogen odors integrated into different responses in the brain. We hypothesize that pathogen odors not only activate immune responses but also induce avoidance behavior. Moreover, we hypothesized that pathogen olfactory responses are modulated by neurosteroids at different times in different parts of the brain. We used a two-choice maze test to determine whether inactivated Yersinia ruckeri elicits aversive behavior. Furthermore, to check if behavioral and immune responses are modulated by neurosteroids, we performed a second experiment where we nasally administered inactivated Y. ruckeri to rainbow trout. After that, the nose, olfactory bulb, cerebellum, and optic tectum were collected at four different time points (15 min, 4 hours, 24 hours, and 7 days) and samples were extracted to measure gene expression of several steroidogenic enzymes ( cyp19a1, 3βHSD, 11HSD, and 17HSD) and fish production of neurosteroids (e.g. cortisol, estradiol, and progesterone). We found that rainbow trout actively avoids pathogen odors. Moreover, we found a different expression of neuro steroidogenic enzymes at different brain areas and times post-exposure. Fish exposed to pathogen odor express a significant increase (ANOVA 2 factor, P<0.05) of cyp19a1 (involved in estradiol synthesis) as soon as 15 min in the nose and olfactory bulb, and 4 hours post-exposure in the cerebellum and optic tectum. This gene expression was parallel to a significant increase of estradiol in the nose, bulb, and rest of the brain between 15 min and 4 hours. Moreover, there was a significant increase of 11HSD and 17HSD (related to the production of testosterone, cortisol, and corticosterone) 4 hours after exposure in the nose and cerebellum but a significant decrease in the olfactory bulb and optic tectum. These gene expression patterns were parallel o an increase of cortisol in the nose and olfactory bulb. Finally, we found a significant increase of 3βHSD (involved in the first steps of steroidogenesis) after 24 hours in the nose and olfactory bulb, although we didn’t find an increase in steroid production in our preliminary assays. Our results showed that exposure to pathogen odors activates different neuro steroidogenic pathways at different times after exposure, and at different areas of the brain. These findings pinpoint the use of the sense of smell by fish to control behavioral and immune responses to pathogens, with neurosteroids playing a key role in modulating and integrating these olfactory responses. This material is based upon work supported by the National Science Foundation under Grant No. 1755348 This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
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Thomas, Anil. "Understanding the Function & Formation of Memory and the Application of Neurolinguistics programing to Reduce Fears, Traumas and Phobias." International Journal of Neurolinguistics & Gestalt Psychology 1, nr 1 (2021). http://dx.doi.org/10.52522/ijngp.v1i1.1.
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This research is based on the idea that a link exists between memories and phobias, fears and traumas and mainly they can be reduced in one’s life by manipulating negative memories, the encoding process, and by using NLP as a therapy and its techniques like the Swish Technique or the Visual-Kinesthetic Dissociation Technique to overcome and remove those very phobias, traumas and fears. Since memory and cognition form an important part of the individual’s life because of the functions it performs the focus of this articles mainly lies surrounding this topic and how NLP can prove to be useful. The encoding process in the memory takes place through different representational systems that are a part of Neuro- Linguistic Programming (NLP). Since NLP lists visual, auditory, kinesthetic, olfactory and gustatory as a part of this system, an attempt is made to explain how through these systems and its sub modalities (finer distinctions of the representational system) memories are formed and how emotions play a role in determining the retrieval of a particular memory and how that in turn leads to the formation of phobias, irrational fears and traumas like the fear of heights, water, etc or a traumatic event like the death of a loved one due to a disease or accident and in order to achieve all of this secondary researches, data analyses and information tools were used.
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Nemade, S. M., S. P. Kakad, S. J. Kshirsagar i T. R. Padole. "Development of nanoemulsion of antiviral drug for brain targeting in the treatment of neuro-AIDS". Beni-Suef University Journal of Basic and Applied Sciences 11, nr 1 (26.11.2022). http://dx.doi.org/10.1186/s43088-022-00319-8.
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Abstract Background Delivery of drugs via the nasal route directly to the brain utilizing the olfactory pathway is purportedly known to be a more efficient method to deliver neuro-therapeutics to the brain by circumventing the BBB, thereby increasing the bioavailability of these drugs in the brain. The main objective of the project work is to improve the bioavailability of the antiretroviral drug and to minimize the side effects of this therapy which are observed at the higher side in the chronic HIV treatment. The advantage of nasal drug delivery is its noninvasiveness and self-administration. Nanoformulation provides fast onset of action and helps to achieve site-specific delivery. In the current work, nanoemulsion formulation was developed with a ternary phase system. In vitro characterization of nanoemulsion was performed. Result Optimized batch B2 had a zeta potential of − 18.7 mV showing a stable emulsion system and a particle size of 156.2 nmin desirable size range. Batch B2 has the least variation in globule size with PDI 0.463. Results from ex vivo studies revealed that developed nanoemulsion (B2) possessed a higher rate of drug release compared to other formulations. Conclusion Phase diagrams indicated more width of the nanoemulsion region with an increase in surfactant ratio. Stable nanoemulsion was prepared with a combination of surfactant and co-surfactants. Nanoemulsions could prove one of the best alternatives for brain delivery of potent medications. Graphical Abstract
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Aparna S, Maya Balakrishnan i Giby Thomas. "ROLE OF NASYA IN THE MANAGEMENT OF DYSFUNCTIONAL UTERINE BLEEDING - A REVIEW". International Journal of Ayurveda and Pharma Research, 18.03.2021, 68–71. http://dx.doi.org/10.47070/ijapr.v9i2.1815.
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Regular menstrual cycles with adequate quantity and duration of bleeding indicate good reproductive health, with variations in these being reflected as menorohagia, oligomenorrbea, dysmenorrbea, PCOD, infertility etc. Dysfunctional uterine bleeding is particularly common during adolescence and perimenopausal periods. It has been defined as a state of excessive uterine bleeding without clinically detectable organic, systemic and iatrogenic causes. DUB is caused by the abnormal functioning of hypothalamo – pituitary – ovarian axis.
Nasya is a term applied generally when the medicine is administered through the nasal passage. It is considered as the most specific Panchakarama therapy used for the diseases of Siras (head) or Urdva jatru region, as nasal passage is regarded as the gateway to the head. In the present article the possible role of Nasya in the management of dysfunctional uterine bleeding is discussed. Nasya indirectly work on the entire body by improving the functioning of central nervous system and endocrine glands. The neurons which stimulate production of GnRH, originates from the olfactory area and GnRH is the regulator of gonadotropin hormones. The hormones of menstruation are under the control of these secreted by the pituitary. Nasya which is considered as having direct action on neuro-endocrinological system may regulate HPO axis and normalize the menstruation.
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Shaykevich, Sarah, Russell W. Chan, Chandni Rana, Mohamed Eltaeb, Justin P. Little, Daniel Razansky, Kevin C. Chan i Shy Shoham. "Optoacoustic imaging of the glymphatic system". Veins and Lymphatics 11, nr 1 (23.11.2022). http://dx.doi.org/10.4081/vl.2022.10967.
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Background: The glymphatic system is a brain waste clearance system mediated via cerebrospinal fluid (CSF) flow,1 with implications for influence on neurodegenerative diseases.2 Most preclinical glymphatic studies employ fluorescence imaging, which provides higher specificity, but a smaller field-of-view (FOV), or magnetic resonance imaging (MRI), which provides brain-wide FOV, but lower specificity. Functional optoacoustic neuro-tomography3 (FONT) offers a larger FOV compared to classical optical methods, and higher specificity compared to MRI. However, FONT has not yet been applied to probe the glymphatic system. In this study, we used fluorescence and optoacoustic imaging of a near-infrared dye, Janelia Fluor 669 (JF669), to track CSF and multimodal CSF-hemodynamic flows in mice.
Methods: After observing strong fluorescence and optoacoustic signatures of JF669 in phantom experiments, we performed a series of in vivo experiments in isoflurane-anesthetized C57BL/6 mice (n=3 fluorescence and n=4 FONT experiments, respectively) (Figure 1A). The lumbar injection was applied to deliver JF669 at a rate of 2 µL/min for 30 minutes. A polyethylene tube was placed intrathecally at the lumbar region (L4-L5). The scalp was removed. Fluorescence or FONT images were obtained every 5 minutes after injection.
Results: Fluorescence imaging and FONT probe CSF flow Images (Figure 1B) and time traces (Figure 1C) revealed time-dependent anatomical routes of paravascular influx, including the transport along the olfactory artery (OFA), superior cerebellar artery (SCA), and bilateral middle cerebral artery (MCA). For FONT imaging, since the OFA showed strong fluorescence (Figure 1B), we positioned the ultrasound transducer array at the anterior of the mouse brain with a FOV of 5x5 mm2 (Figure 1A). Standard filtered back-projection reconstruction was applied. Besides the OFA route of the paravascular influx, the dynamic images (Figure 1D) and time-traces (Figure 1E) also revealed time-dependent anatomical routes of CSF-interstitial fluid (ISF) exchange in the olfactory bulb (OFB) and paravascular efflux in the superior sagittal sinus (SSS) and the bilateral inferior cerebral vein (ICV). Next, we studied the aquaporin-4 (AQP4) dependence of glymphatic flow by subcutaneously injecting AQP4 inhibitor TGN020, in addition to the prior procedures. Under fluorescence imaging and FONT, we observed that TGN020 significantly decreased and spatially restricted the spread of JF669 in the brain. FONT spectral unmixing separates CSF and blood We swept the OPO through 680 nm to 750 nm, with 10 nm steps at 10 Hz in the phantom and in each animal. The multispectral reconstructions were unmixed using the known absorption spectra of hemoglobin and the JF669 OA spectrum obtained from the phantom.4 This enabled the separation of blood and JF669 signal (Figure 1D).
Conclusions: We characterized anatomical routes of paravascular influx (OFA), CSF-ISF exchange (OFB) and paravascular efflux using FONT, while fluorescence imaging only enabled visualization of the paravascular influx. We thus demonstrated the feasibility and advantages of FONT for probing the glymphatic system. These findings present great opportunities for monitoring and understanding the glymphatic system during development, aging, disease, pharmacological interventions and genetic modifications.
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Al-kuraishy, Hayder M., Ali I. Al-Gareeb, Abdur Rauf, Fahad A. Alhumaydhi, Małgorzata Kujawska i Gaber El-Saber Batiha. "Mechanistic insight and possible mechanism of seizure in Covid-19: The nuances and focal points". CNS & Neurological Disorders - Drug Targets 21 (17.05.2022). http://dx.doi.org/10.2174/1871527321666220517115227.
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Abstract: Coronavirus disease 2019 (Covid-19) is a primary respiratory disease with an alarming impact on citizens worldwide. Triggered by severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2), Covid-19 may present with a variety of neurological symptoms, including headache, changes in consciousness and seizure/convulsion. SARS-CoV-2 has neuroinvasive and neurotropic abilities through neuronal angiotensin converting enzyme 2 (ACE2), which is highly expressed in both neuronal and glial cells. This neuroinvasive ability of SARS-CoV-2 leads to neuroinflammation and neuronal hyperexcitability with the consequent risk of seizure. Olfactory neurons are looked as an exceptional neuronal pathway for neuro-invasion and neurotropism of respiratory viruses to access the central nervous system (CNS) from the nasal cavity, leading to neuronal injury and neuroinflammation. Although neuronal ACE2 has been widely studied, other receptors for SARS-CoV-2 in the brain have been proposed to mediate viral-neuronal interaction with subsequent neurological squeals. Thus, this article aims to provide a critical view that epileptic seizures are a common neurological finding associated with Covid-19 and may be the initial presentation of Covid-19 even in the absence of respiratory symptoms and no pulmonary involvement.
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Iovino, Michele, Tullio Messana, Anna Tortora, Consuelo Giusti, Giuseppe Lisco, Vito Angelo Giagulli, Edoardo Guastamacchia, Giovanni De Pergola i Vincenzo Triggiani. "Oxytocin Signaling Pathway: From Cell Biology To Clinical Implications." Endocrine, Metabolic & Immune Disorders - Drug Targets 20 (20.05.2020). http://dx.doi.org/10.2174/1871530320666200520093730.
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Background: In addition to the well known role played on lactation and parturition, Oxytocin (OT) and OT receptor (OTR) are involved in many other aspects such as the control of maternal and social behavior, the regulation of the growth of the neocortex, the maintenance of blood supply to the cortex, the stimulation of limbic olfactory area to mother-infant recognition bond, and the modulation of the autonomic nervous system via vagal pathway. Moreover, OT and OTR show anti-inflammatory, anti-oxidant, anti-pain, antidiabetic, anti-dyslipidemic and anti-atherogenic effects. Objective: The aim of this narrative review is to summarize the main data coming from the literature dealing with the role of OT and OTR in physiology and pathologic conditions focusing on the most relevant aspects. Methods: Appropriate keywords and MeSH terms were identified and searched in Pubmed. Finally, references of original articles and reviews were examined. Results: We report the most significant and updated data about the role played by OT and OTR in physiology and in different clinical context. Conclusion: Emerging evidence indicates the involvement of OT system in several pathophysiological mechanisms influencing brain anatomy, cognition, language, sense of safety and trust and maternal behavior, with a possible use of exogenous administered OT in the treatment of specific neuro-psychiatric conditions. Furthermore, it modulates pancreatic β-cell responsiveness and lipid metabolism leading to possible therapeutic use in diabetic and dyslipidemic patients and for limiting and even reversing atherosclerotic lesions.
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Voruz, Philippe, Alexandre Cionca, Isabele Jacot de Alcântara, Anthony Nuber-Champier, Gilles Allali, Lamyae Benzakour, Marine Thomasson i in. "Functional connectivity underlying cognitive and psychiatric symptoms in post-COVID-19 syndrome: is anosognosia a key determinant?" Brain Communications 4, nr 2 (1.03.2022). http://dx.doi.org/10.1093/braincomms/fcac057.
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Abstract Lack of awareness of cognitive impairment (i.e. anosognosia) could be a key factor for distinguishing between neuropsychological post-COVID-19 condition phenotypes. In this context, the 2-fold aim of the present study was to (i) establish the prevalence of anosognosia for memory impairment, according to the severity of the infection in the acute phase and (ii) determine whether anosognosic patients with post-COVID syndrome have a different cognitive and psychiatric profile from nosognosic patients, with associated differences in brain functional connectivity. A battery of neuropsychological, psychiatric, olfactory, dyspnoea, fatigue and quality-of-life tests was administered 227.07 ± 42.69 days post-SARS-CoV-2 infection to 102 patients (mean age: 56.35 years, 65 men, no history of neurological, psychiatric, neuro-oncological or neurodevelopmental disorder prior to infection) who had experienced either a mild (not hospitalized; n = 45), moderate (conventional hospitalization; n = 34) or severe (hospitalization with intensive care unit stay and mechanical ventilation; n = 23) presentation in the acute phase. Patients were first divided into two groups according to the presence or absence of anosognosia for memory deficits (26 anosognosic patients and 76 nosognosic patients). Of these, 49 patients underwent an MRI. Structural images were visually analysed, and statistical intergroup analyses were then performed on behavioural and functional connectivity measures. Only 15.6% of patients who presented mild disease displayed anosognosia for memory dysfunction, compared with 32.4% of patients with moderate presentation and 34.8% of patients with severe disease. Compared with nosognosic patients, those with anosognosia for memory dysfunction performed significantly more poorly on objective cognitive and olfactory measures. By contrast, they gave significantly more positive subjective assessments of their quality of life, psychiatric status and fatigue. Interestingly, the proportion of patients exhibiting a lack of consciousness of olfactory deficits was significantly higher in the anosognosic group. Functional connectivity analyses revealed a significant decrease in connectivity, in the anosognosic group as compared with the nosognosic group, within and between the following networks: the left default mode, the bilateral somatosensory motor, the right executive control, the right salient ventral attention and the bilateral dorsal attention networks, as well as the right Lobules IV and V of the cerebellum. Lack of awareness of cognitive disorders and, to a broader extent, impairment of the self-monitoring brain system, may be a key factor for distinguishing between the clinical phenotypes of post-COVID syndrome with neuropsychological deficits.
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Beyer, Felix, Wichard Lüdje, Julian Karpf, Gesine Saher i Ruth Beckervordersandforth. "Distribution of Aldh1L1-CreERT2 Recombination in Astrocytes Versus Neural Stem Cells in the Neurogenic Niches of the Adult Mouse Brain". Frontiers in Neuroscience 15 (7.09.2021). http://dx.doi.org/10.3389/fnins.2021.713077.
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In the adult central nervous system, neural stem cells (NSCs) reside in two discrete niches: the subependymal zone (SEZ) of the lateral ventricle and the subgranular zone (SGZ) of the dentate gyrus (DG). Here, NSCs represent a population of highly specialized astrocytes that are able to proliferate and give rise to neuronal and glial progeny. This process, termed adult neurogenesis, is extrinsically regulated by other niche cells such as non-stem cell astrocytes. Studying these non-stem cell niche astrocytes and their role during adult neuro- and gliogenesis has been hampered by the lack of genetic tools to discriminate between transcriptionally similar NSCs and niche astrocytes. Recently, Aldh1L1 has been shown to be a pan-astrocyte marker and that its promoter can be used to specifically target astrocytes using the Cre-loxP system. In this study we explored whether the recently described Aldh1L1-CreERT2 mouse line (Winchenbach et al., 2016) can serve to specifically target niche astrocytes without inducing recombination in NSCs in adult neurogenic niches. Using short- and long-term tamoxifen protocols we revealed high recombination efficiency and specificity in non-stem cell astrocytes and little to no recombination in NSCs of the adult DG. However, in the SEZ we observed recombination in ependymal cells, astrocytes, and NSCs, the latter giving rise to neuronal progeny of the rostral migratory stream and olfactory bulb. Thus, we recommend the here described Aldh1L1-CreERT2 mouse line for predominantly studying the functions of non-stem cell astrocytes in the DG under physiological and pathological conditions.
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Sarma, Anupam, i Malay K. Das. "Nose to brain delivery of antiretroviral drugs in the treatment of neuroAIDS". Molecular Biomedicine 1, nr 1 (grudzień 2020). http://dx.doi.org/10.1186/s43556-020-00019-8.
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AbstractNeuroAIDS (Neuro Acquired Immunodeficiency Syndrome) or HIV (Human Immunodeficiency Virus) associated neuronal abnormality is continuing to be a significant health issue among AIDS patients even under the treatment of combined antiretroviral therapy (cART). Injury and damage to neurons of the brain are the prime causes of neuroAIDS, which happens due to the ingress of HIV by direct permeation across the blood-brain barrier (BBB) or else via peripherally infected macrophage into the central nervous system (CNS). The BBB performs as a stringent barricade for the delivery of therapeutics drugs. The intranasal route of drug administration exhibits as a non-invasive technique to bypass the BBB for the delivery of antiretroviral drugs and other active pharmaceutical ingredients inside the brain and CNS. This method is fruitful for the drugs that are unable to invade the BBB to show its action in the CNS and thus erase the demand of systemic delivery and thereby shrink systemic side effects. Drug delivery from the nose to the brain/CNS takes very less time through both olfactory and trigeminal nerves. Intranasal delivery does not require the involvement of any receptor as it occurs by an extracellular route. Nose to brain delivery also involves nasal associated lymphatic tissues (NALT) and deep cervical lymph nodes. However, very little research has been done to explore the utility of nose to brain delivery of antiretroviral drugs in the treatment of neuroAIDS. This review focuses on the potential of nasal route for the effective delivery of antiretroviral nanoformulations directly from nose to the brain.
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Ermis, Ummehan, Marcus Immanuel Rust, Julia Bungenberg, Ana Costa, Michael Dreher, Paul Balfanz, Gernot Marx i in. "Neurological symptoms in COVID-19: a cross-sectional monocentric study of hospitalized patients". Neurological Research and Practice 3, nr 1 (12.03.2021). http://dx.doi.org/10.1186/s42466-021-00116-1.
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Abstract Background The SARS-Coronavirus-2 (SARS-CoV-2) invades the respiratory system, causing acute and sometimes severe pulmonary symptoms, but turned out to also act multisystematically with substantial impact on the brain. A growing number of studies suggests a diverse spectrum of neurological manifestations. To investigate the spectrum of symptoms, we here describe the neurological manifestations and complications of patients with proven SARS-CoV-2 infection who have been hospitalized at the RWTH University Hospital Aachen, Germany. Methods Between March and September 2020, we evaluated common symptoms, clinical characteristics, laboratory (including cerebrospinal fluid (CSF) analysis), radiological, and electroencephalography (EEG) data from 53 patients admitted with a positive SARS-CoV-2 polymerase chain reaction (PCR). We used the Montreal Cognitive Assessment Test (MoCA) to screen for cognitive impairment, when feasible. We compared critically ill and non-critically ill patients categorized according to the presence of Acute Respiratory Distress Syndrome (ARDS). Results Major clinical neurological features of hospitalized COVID-19 patients were coordination deficits (74%), cognitive impairment (61.5%), paresis (47%), abnormal reflex status (45%), sensory abnormalities (45%), general muscle weakness and pain (32%), hyposmia (26%), and headache (21%). Patients with ARDS were more severely affected than non-ADRS patients. 29.6% of patients with ARDS presented with subarachnoid bleedings, and 11.1% showed ischemic stroke associated with SARS-CoV-2 infection. Cognitive deficits mainly affected executive functions, attention, language, and delayed memory recall. We obtained cerebrospinal fluid (CSF) by lumbar puncture in nine of the 53 patients, none of which had a positive SARS-CoV-2 PCR. Conclusions In line with previous findings, our results provide evidence for a range of SARS-CoV-2-associated neurological manifestations. 26% of patients reported hyposmia, emphasizing the neuro-invasive potential of SARS-CoV-2, which can enter the olfactory bulb. It can therefore be speculated that neurological manifestations may be caused by direct invasion of the virus in the CNS; however, PCR did not reveal positive intrathecal SARS-CoV-2. Therefore, we hypothesize it is more likely that the para-infectious severe pro-inflammatory impact of COVID-19 is responsible for the neurological deficits including cognitive impairment. Future studies with comprehensive longitudinal assessment of neurological deficits are required to determine potential long-term complications of COVID-19.