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Advanced Science (Weinheim,... Nov 2023Addressing the challenge of promoting directional axonal regeneration in a hostile astrocytic scar, which often impedes recovery following spinal cord injury (SCI),...
A Novel Magnetic Responsive miR-26a@SPIONs-OECs for Spinal Cord Injury: Triggering Neural Regeneration Program and Orienting Axon Guidance in Inhibitory Astrocytic Environment.
Addressing the challenge of promoting directional axonal regeneration in a hostile astrocytic scar, which often impedes recovery following spinal cord injury (SCI), remains a daunting task. Cell transplantation is a promising strategy to facilitate nerve restoration in SCI. In this research, a pro-regeneration system is developed, namely miR-26a@SPIONs-OECs, for olfactory ensheathing cells (OECs), a preferred choice for promoting nerve regeneration in SCI patients. These entities show high responsiveness to external magnetic fields (MF), leading to synergistic multimodal cues to enhance nerve regeneration. First, an MF stimulates miR-26a@SPIONs-OECs to release extracellular vesicles (EVs) rich in miR-26a. This encourages axon growth by inhibiting PTEN and GSK-3β signaling pathways in neurons. Second, miR-26a@SPIONs-OECs exhibit a tendency to migrate and orientate along the direction of the MF, thereby potentially facilitating neuronal reconnection through directional neurite elongation. Third, miR-26a-enriched EVs from miR-26a@SPIONs-OECs can interact with host astrocytes, thereby diminishing inhibitory cues for neurite growth. In a rat model of SCI, the miR-26a@SPIONs-OECs system led to significantly improved morphological and motor function recovery. In summary, the miR-26a@SPIONS-OECs pro-regeneration system offers innovative insights into engineering exogenous cells with multiple additional cues, augmenting their efficacy for stimulating and guiding nerve regeneration within a hostile astrocytic scar in SCI.
Topics: Rats; Humans; Animals; Astrocytes; Cicatrix; Axon Guidance; Glycogen Synthase Kinase 3 beta; Nerve Regeneration; Spinal Cord Injuries; Magnetic Phenomena; MicroRNAs
PubMed: 37789583
DOI: 10.1002/advs.202304487 -
Cell Transplantation 2023In the past decades, the properties of olfactory ensheathing cells (OECs) have been widely investigated. Studies have shown that transplantation of OECs cultured from...
In the past decades, the properties of olfactory ensheathing cells (OECs) have been widely investigated. Studies have shown that transplantation of OECs cultured from the olfactory bulb mediates axonal regeneration, remyelination and restores lost functions in experimental central nervous system (CNS) injury models. Autologously sourcing the cells from the nasal mucosa or the olfactory bulb to treat patients with spinal cord injuries would be ideal, but the cell yield achieved may be inadequate to cover the surface area of the lesions typically encountered in human spinal cord contusion injuries. Therefore, banking allogenic cryopreserved olfactory bulb cells from donors or generating cell lines could provide a marked increase in cell stock available for transplantation. This study is undertaken in two control and two intervention groups. The control groups have lesions alone and lesions with collagen gel but without cells. The intervention groups have either transplantation of primary cultured olfactory bulb OECs (bOECs) encapsulated in collagen gel or cryopreserved bulb OECs (CbOECs) encapsulated in collagen gel. Here, we report that transplantation of cryopreserved rat bOECs encapsulated in collagen restored the loss of function in a vertical climbing test in a unilateral C6-T1 dorsal root injury model. The loss of function returns in 80% of rats with injuries in about 3 weeks comparable to that we observed after transplantation of primary cultured bOECs. The regeneration axons induced by the transplant are identified by neurofilament antibodies and ensheathed by OECs. Our results indicate that cryopreserved OECs retain their properties of inducing axon regeneration and restoring loss of function in the experimental model. This is a step forward to translate the research into future clinical applications.
Topics: Rats; Humans; Animals; Axons; Cell Transplantation; Nerve Regeneration; Spinal Cord Injuries; Olfactory Bulb; Collagen
PubMed: 37771302
DOI: 10.1177/09636897231199319 -
Medicina (Kaunas, Lithuania) Aug 2023: Hypo/anosmia is a characteristic symptom of COVID-19 infection. The aim of this study is to investigate the time of smell recovery and to identify a possible order of... (Observational Study)
Observational Study
: Hypo/anosmia is a characteristic symptom of COVID-19 infection. The aim of this study is to investigate the time of smell recovery and to identify a possible order of perception recovery of different odors in COVID-19 patients. : A prospective observational study was conducted on not hospitalized COVID-19 patients, selected according to eligible criteria. The study was approved by the Ethical Committee. A questionnaire formulated by our team was submitted to patients in order to know the duration of the hypo/anosmia and hypo/ageusia and the order of odor recovery: vanillin (mixed olfactory/gustatory substances), phenyl ethyl alcohol (rosewater) (pure olfactory substances), eucalyptol (mixed olfactory/trigeminal substances), and eugenol (mixed olfactory/trigeminal/gustatory substances). : 181 patients were included. Hypo/ageusia and hypo/anosmia lasted on average 10.25 (±8.26) and 12.8 (±8.80) days, respectively. The most frequent odor recovery sequence was: (1) phenyl ethyl alcohol; (2) eucalyptol; (3) vanillin; and (4) eugenol. In COVID-19 patients, hypo/anosmia occurs more often in women and at a young age. : This preliminary investigation highlighted novel data: there is a chronological order in perception recovery of different olfactory substances and, therefore, in the restoration of the various sensitive nerve pathways involved in the sense of smell.
Topics: Humans; Female; Smell; Anosmia; Ageusia; Eucalyptol; Eugenol; COVID-19; Phenylethyl Alcohol
PubMed: 37763630
DOI: 10.3390/medicina59091511 -
Haploinsufficiency of in Mice Selectively Impairs Target Odor Recognition in Novel Background Odors.The Journal of Neuroscience : the... Nov 2023Individuals with mutations in a single copy of the SHANK3 gene present with social interaction deficits. Although social behavior in mice depends on olfaction, mice with...
Individuals with mutations in a single copy of the SHANK3 gene present with social interaction deficits. Although social behavior in mice depends on olfaction, mice with mutations in a single copy of the gene do not have olfactory deficits in simple odor identification tasks (Drapeau et al., 2018). Here, we tested olfaction in mice with mutations in a single copy of the gene (Peça et al., 2011) using a complex odor task and imaging in awake mice. Average glomerular responses in the olfactory bulb of were correlated with WT mice. However, there was increased trial-to-trial variability in the odor responses for mice. Simulations demonstrated that this increased variability could affect odor detection in novel environments. To test whether performance was affected by the increased variability, we tested target odor recognition in the presence of novel background odors using a recently developed task (Li et al., 2023). Head-fixed mice were trained to detect target odors in the presence of known background odors. Performance was tested using catch trials where the known background odors were replaced by novel background odors. We compared the performance of eight mice (five males, three females) on this task with six WT mice (three males, three females). Performance for known background odors and learning rates were similar between and WT mice. However, when tested with novel background odors, the performance of mice dropped to almost chance levels. Thus, haploinsufficiency of the gene causes a specific deficit in odor detection in novel environments. Our results are discussed in the context of other mouse models and have implications for understanding olfactory function in neurodevelopmental disorders. People and mice with mutations in a single copy in the synaptic gene Shank3 show features seen in autism spectrum disorders, including social interaction deficits. Although mice social behavior uses olfaction, mice with mutations in a single copy of Shank3 have so far not shown olfactory deficits when tested using simple tasks. Here, we used a recently developed task to show that these mice could identify odors in the presence of known background odors as well as wild-type mice. However, their performance fell below that of wild-type mice when challenged with novel background odors. This deficit was also previously reported in the Cntnap2 mouse model of autism, suggesting that odor detection in novel backgrounds is a general deficit across mouse models of autism.
Topics: Humans; Male; Female; Mice; Animals; Odorants; Haploinsufficiency; Smell; Social Behavior; Olfactory Bulb; Microfilament Proteins; Nerve Tissue Proteins
PubMed: 37739796
DOI: 10.1523/JNEUROSCI.0255-23.2023 -
Neurosurgical Review Sep 2023Optic canal unroofing (OCU) has gradually become a routine technique for tuberculum sellae meningiomas (TSMs) resection. This meta-analysis aimed to evaluate the... (Meta-Analysis)
Meta-Analysis Review
Optic canal unroofing (OCU) has gradually become a routine technique for tuberculum sellae meningiomas (TSMs) resection. This meta-analysis aimed to evaluate the efficacy and safety of OCU. A systematic review and meta-analysis of the published literature on this topic from 2003 to 2023 were conducted in accordance with the PRISMA guidelines. Rigorous statistical analysis with a p-value was performed for related change in visual improvement, gross total resection (GTR), visual deterioration, and olfactory nerve damage. The study included 15 articles with 384 patients in whom OCU was performed by the transcranial approach (TCA) or the endoscopic endonasal approach (EEA). Of these, 341 patients had preoperative visual loss, and 266 patients had postoperative visual recovery. The overall rate of visual improvement was 0.803 (95% CI: 0.733-0.874, p < 0.01). The rate of visual improvement in the EEA and TCA groups was 0.884 (95% CI: 0.803-0.965, p < 0.01) and 0.788 (95% CI: 0.700-0.875, p < 0.01). Further analysis of classification shows that the rate of visual improvement in Type I: < 2 cm was 0.889(95% CI: 0.739-0.969), Type II:2-4 cm was 0.844(95% CI: 0.755-0.910), Type III: > 4 cm was 0.500(95% CI: 0.068-0.932) and the total was 0.853(95% CI: 0.779-0.927 p < 0.01) with low heterogeneity of I = 20.80%.Twelve studies separately reported GTR with OCU was 293; the rate of GTR was 0.911 (95% CI: 0.848-0.961, p < 0.01). And the rate of GTR in Type I: < 2 cm was 0.933(95% CI: 0.817-0.986), Type II:2-4 cm was 0.880(95% CI: 0.800-0.936), Type III: > 4 cm was 0.600(95% CI: 0.147-0.947). The total was 0.897(95% CI: 0.830-0.965 p < 0.01) with low heterogeneity of I = 34.57%. The related complications of OCU were visual deterioration and olfactory nerve damage. Visual decline was reported in nine studies, and the rate was 0.077 (95% CI: 0.041-0.113, p < 0.01). Six studies reported olfactory nerve damage, and the overall rate was 0.054 (95% CI: 0.019-0.090, p < 0.01). OCU could significantly recover preoperative impaired vision and make GTR easier to achieve, which was also a safe and effective technique in TSM.
Topics: Humans; Meningioma; Postoperative Period; Skull Base Neoplasms; Meningeal Neoplasms
PubMed: 37698750
DOI: 10.1007/s10143-023-02151-9 -
BioRxiv : the Preprint Server For... Sep 2023During embryonic development, the olfactory placode (OP) generates migratory neurons, including olfactory pioneer neurons, cells of the terminal nerve (TN),...
UNLABELLED
During embryonic development, the olfactory placode (OP) generates migratory neurons, including olfactory pioneer neurons, cells of the terminal nerve (TN), Gonadotropin-releasing hormone-1 (GnRH-1) neurons, and other uncharacterized neurons. Pioneer neurons from the olfactory placode induce olfactory bulb morphogenesis. In mice, GnRH-1 neurons appear in the olfactory system around mid-gestation and migrate via the terminal nerve axons to different brain regions. The GnRH-1 neurons are crucial in controlling the hypothalamic-pituitary-gonadal (HPG) axis. Kallmann syndrome is characterized by impaired olfactory system development, defective olfactory bulbs, defective secretion of GnRH-1, and infertility. The precise mechanistic link between the olfactory system and GnRH-1 development remains unclear. Studies in humans and mice highlight the importance of the Prokineticin-2/Prokineticin-Receptor-2 (Prokr2) signaling pathway in olfactory bulb morphogenesis and GnRH-1 neuronal migration. loss-of-function mutations can cause Kallmann syndrome, and hence the Prokr2 signaling pathway represents a unique model to decipher the olfactory/GnRH-1 connection. We discovered that Prokr2 is expressed in the TN neurons during the critical period of GnRH-1 neuron formation, migration, and induction of olfactory bulb morphogenesis. Single-cell RNA sequencing identified that the TN is formed by neurons that are distinct from the olfactory neurons. The TN neurons express multiple genes associated with KS. Our study suggests that the aberrant development of pioneer/TN neurons might cause the KS spectrum.
KEY POINTS
1) Pioneer or terminal nerve neurons play a crucial role in initiating the development of the olfactory bulbs. We found that the Prokineticin Receptor-2 gene, associated with Kallmann syndrome, is expressed by the olfactory pioneer/terminal nerve neurons.2) We genetically traced, isolated, and conducted Single-cell RNA sequencing on terminal nerve neurons of rodents. This analysis revealed a significant enrichment of gene expression related to Kallmann syndrome.3) Our study indicates that the investigation of Pioneer/terminal nerve neurons should be a pivotal focal point for comprehending developmental defects affecting olfactory and GnRH-1 systems.
PubMed: 37693459
DOI: 10.1101/2023.08.31.555770 -
International Journal of Molecular... Aug 2023One of the most prevalent causes of olfactory loss includes traumatic brain injury with subsequent shearing of olfactory axons at the level of the cribriform plate...
One of the most prevalent causes of olfactory loss includes traumatic brain injury with subsequent shearing of olfactory axons at the level of the cribriform plate (anterior skull base). Scar tissue at this level may prevent axonal regrowth toward the olfactory bulb. Currently, there is no cure for this debilitating and often permanent condition. One promising therapeutic concept is to implant a synthetic scaffold with growth factors through the cribriform plate/scar tissue to induce neuroregeneration. The first step toward this goal is to investigate the optimum conditions (growth factors, extracellular matrix proteins) to boost this regeneration. However, the lack of a specifically tailored in vitro model and an automated procedure for quantifying axonal length limits our ability to address this issue. The aim of this study is to create an automated quantification tool to measure axonal length and to determine the ideal growth factors and extracellular proteins to enhance axonal regrowth of olfactory sensory neurons in a mouse organotypic 2D model. We harvested olfactory epithelium (OE) of C57BL/6 mice and cultured them during 15 days on coverslips coated with various extracellular matrix proteins (Fibronectin, Collagen IV, Laminin, none) and different growth factors: fibroblast growth factor 2 (FGF2), brain-derived neurotrophic factor (BDNF), glial cell-derived neurotrophic factor (GDNF), nerve growth factor (NGF), retinoic acid (RA), transforming growth factor β (TGFβ), and none. We measured the attachment rate on coverslips, the presence of cellular and axonal outgrowth, and finally, the total axonal length with a newly developed automated high-throughput quantification tool. Whereas the coatings did not influence attachment and neuronal outgrowth rates, the total axonal length was enhanced on fibronectin and collagen IV ( = 0.001). The optimum growth factor supplementation media to culture OE compared to the control condition were as follows: FGF2 alone and FGF2 from day 0 to 7 followed by FGF2 in combination with NGF from day 7 to 15 ( < 0.0001). The automated quantification tool to measure axonal length outperformed the standard Neuron J application by reducing the average analysis time from 22 to 3 min per specimen. In conclusion, robust regeneration of murine olfactory neurons in vitro can be induced, controlled, and efficiently measured using an automated quantification tool. These results will help advance the therapeutic concept closer toward preclinical studies.
Topics: Animals; Mice; Mice, Inbred C57BL; Olfactory Receptor Neurons; Fibronectins; Cicatrix; Fibroblast Growth Factor 2; Nerve Growth Factor; Axons; Extracellular Matrix Proteins; Collagen Type IV; Culture Media
PubMed: 37629041
DOI: 10.3390/ijms241612863 -
Frontiers in Neurology 2023COVID-19 was first reported in November 2019 in China and rapidly spread across the globe. COVID-19 causes neurologic symptoms and complications, which may persist even...
INTRODUCTION
COVID-19 was first reported in November 2019 in China and rapidly spread across the globe. COVID-19 causes neurologic symptoms and complications, which may persist even after recovery in patients. The objective of this research was to determine the involvement of cranial nerves in COVID-19 survivors.
METHOD
This was a retrospective study. The study was conducted between March and July of 2022. The analysis included 98 patients with a certain positive polymerase chain reaction. SPSS software version 19 was utilized for data analysis.
RESULTS
The average age of the participants was 40.47 years (8.81). The olfactory nerve was found to be the most frequently involved cranial nerve (36.7%). Over 20% of participants had a taste disorder. The findings from the regression analysis indicated that lung involvement and age have a direct and significant relationship with cranial nerve involvement and can serve as its predictors ( = 0.001).
CONCLUSION
It seems that cranial nerve involvement was sustained in COVID-19 patients who survived. In addition, elderly patients and patients with severe illnesses were more likely to show cranial symptoms. It is necessary to monitor COVID-19 survivors for neurological symptoms.
PubMed: 37602247
DOI: 10.3389/fneur.2023.1182543 -
BioRxiv : the Preprint Server For... Aug 2023The olfactory nerve, also known as cranial nerve I, is known to have exclusive ipsilateral projections to primary olfactory cortical structures. It is still unclear...
The olfactory nerve, also known as cranial nerve I, is known to have exclusive ipsilateral projections to primary olfactory cortical structures. It is still unclear whether these projections also correspond to functional pathways of odor processing. In an olfactory functional magnetic resonance imaging (fMRI) study of twenty young healthy subjects with a normal sense of smell, we tested whether nostril specific stimulation with phenyl ethyl alcohol (PEA), a pure olfactory stimulant, asymmetrically activates primary or secondary olfactory-related brain structures such as primary olfactory cortex, entorhinal cortex, and orbitofrontal cortex. The results indicated that without a challenging olfactory task, passive (no sniffing) and active (with sniffing) nostril-specific PEA stimulation did not produce asymmetrical fMRI activation in olfactory cortical structures.
PubMed: 37577649
DOI: 10.1101/2023.08.01.551475