The concept of neurons as irreplaceable cells does not hold true today. Experiments and evidence of neurogenesis, also, in the adult brain give hope that some compounds or drugs can enhance this ...process, helping to reverse the outcomes of diseases or traumas that once were thought to be everlasting. Cannabinoids, both from natural and artificial origins, already proved to have several beneficial effects (e.g., anti-inflammatory, anti-oxidants and analgesic action), but also capacity to increase neuronal population, by replacing the cells that were lost and/or regenerate a damaged nerve cell. Neurogenesis is a process which is not highly represented in literature as neuroprotection, though it is as important as prevention of nervous system damage, because it can represent a possible solution when neuronal death is already present, such as in neurodegenerative diseases. The aim of this review is to resume the experimental evidence of phyto- and synthetic cannabinoids effects on neurogenesis, both in vitro and in vivo, in order to elucidate if they possess also neurogenetic and neurorepairing properties.
Alzheimer's disease (AD) is a neurodegenerative disorder affecting millions of people around the world. The two main pathological mechanisms underlying the disease are beta-amyloid (Aβ) plaques and ...intracellular neurofibrillary tangles (NFTs) of Tau proteins in the brain. Their reduction has been associated with slowing of cognitive decline and disease progression. Several antibodies aimed to target Aβ or Tau in order to represent hope for millions of patients, but only a small number managed to be selected to participate in clinical trials. Aducanumab is a monoclonal antibody recently approved by the Food and Drug Administration (FDA), which, targeting (Aβ) oligomers and fibrils, was able to reduce Aβ accumulation and slow the progression of cognitive impairment. It was also claimed to have an effect on the second hallmark of AD, decreasing the level of phospho-Tau evaluated in cerebrospinal fluid (CSF) and by positron emission tomography (PET). This evidence may represent a turning point in the development of AD-efficient drugs.
As the human life expectancy increases, age-linked diseases have become more and more frequent. The worldwide increment of dementia cases demands medical solutions, but the current available drugs do ...not meet all the expectations. Recently the attention of the scientific community was attracted by natural compounds, used in ancient medicine, known for their beneficial effects and high tolerability. This review is focused on Ginger (
) and explore its properties against Alzheimer's Disease and Vascular Dementia, two of the most common and devastating forms of dementia. This work resumes the beneficial effects of Ginger compounds, tested in computational in vitro and in vivo models of Alzheimer's Disease and Vascular Dementia, along with some human tests. All these evidences suggest a potential role of the compounds of ginger not only in the treatment of the disease, but also in its prevention.
Microglia coordinate various functions in the central nervous system ranging from removing synaptic connections, to maintaining brain homeostasis by monitoring neuronal function, and clearing protein ...aggregates across the lifespan. Here we investigated whether increased microglial phagocytic activity that clears amyloid can also cause pathological synapse loss. We identified TDP-43, a DNA-RNA binding protein encoded by the Tardbp gene, as a strong regulator of microglial phagocytosis. Mice lacking TDP-43 in microglia exhibit reduced amyloid load in a model of Alzheimer’s disease (AD) but at the same time display drastic synapse loss, even in the absence of amyloid. Clinical examination from TDP-43 pathology cases reveal a considerably reduced prevalence of AD and decreased amyloid pathology compared to age-matched healthy controls, confirming our experimental results. Overall, our data suggest that dysfunctional microglia might play a causative role in the pathogenesis of neurodegenerative disorders, critically modulating the early stages of cognitive decline.
•TDP-43 regulates microglial phagocytosis and clearance of Aβ•Depletion of microglial TDP-43 results in enhanced synapse loss•Depletion of microglial TDP-43 promotes amyloid clearance in a mouse model of AD•TDP-43 pathology is associated with lower amyloid deposition in post-mortem brains
Paolicelli et al. show that TDP-43 is a regulator of microglial phagocytosis. They found that mice lacking microglial TDP-43 display enhanced amyloid clearance but also significant synapse loss. They also show that TDP-43 pathology is associated with reduced amyloid burden in human brains.
Stroke is one of the leading causes of death and disability worldwide, so there is an urgent need to find a therapy for the tragic outcomes of this cerebrovascular disease. Stem cells appeared to be ...a good solution for many conditions, so different experiments were made to establish stem cells as a feasible therapy for stroke. The aim of this review is to analyze the state of the art of stem cell therapy for stroke and if the route of administration could represent a valid adjusting point for ameliorating the therapy's outcome. To obtain this, we searched the scientific literature of the last 10 years for relevant in vitro and in vivo evidence regarding stem cells' potential in stroke therapy. In vitro evidence points to hypoxia, among the preconditioning strategies, as the most used and probably efficient method to enhance cells qualities, while in vivo results raise the question if it is the type of cells or how they are administrated which can make the difference in terms of efficiency. Unfortunately, despite the number of clinical trials, only a few were successfully concluded, demonstrating how urgent the necessity is to translate pre-clinical results into clinics. Since any type of stem cell seems suitable for therapy, the chosen route of administration corresponds to different engraftment rates, distribution and efficiency in terms of the beneficial effects of stem cells. Intravenous administration was widely used for delivering stem cells into the human body, but recently intranasal administration has given promising results in vivo. It allows stem cells to efficiently reach the brain that was precluded to intravenous administration, so it is worth further investigation.
Recently, the scientific community has started to focus on the neurogenic potential of cannabinoids. The phytocompound cannabidiol (CBD) shows different mechanism of signaling on cannabinoid receptor ...1 (CB1), depending on its concentration. In this study, we investigated if CBD may induce in vitro neuronal differentiation after treatment at 5 µM and 10 µM. For this purpose, we decided to use the spinal cord × neuroblastoma hybrid cell line (NSC-34) because of its proliferative and undifferentiated state. The messenger RNAs (mRNAs) expression profiles were tested using high-throughput sequencing technology and Western blot assay was used to determine the number of main proteins in different pathways. Interestingly, the treatment shows different genes associated with neurodifferentiation statistically significant, such as Rbfox3, Tubb3, Pax6 and Eno2. The CB1 signaling pathway is responsible for neuronal differentiation at 10 µM, as suggested by the presence of p-ERK and p-AKT, but not at 5 µM. A new correlation between CBD, neurodifferentiation and retinoic acid receptor-related orphan receptors (RORs) has been observed.
Spinal cord injury affects the lives of millions of people around the world, often causing disability and, in unfortunate circumstances, death. Rehabilitation can partly improve outcomes and only a ...small percentage of patients, typically the least injured, can hope to return to normal living conditions.
is gaining more and more interest in recent years, even though its beneficial properties have been known for thousands of years. Cannabigerol (CBG), extracted from
, is defined as the "mother of all cannabinoids" and its properties range from anti-inflammatory to antioxidant and neuroprotection. Using NSC-34 cells to model spinal cord injury in vitro, our work evaluated the properties of CBG treatments in motor neuron regeneration. While pre-treatment can modulate oxidative stress and increase antioxidant enzyme genes, such as
, decreasing
post-treatment seems to induce regeneration genes by triggering different pathways, such as
via p53 acetylation by
and
and
via
signaling, along with cytoskeletal remodeling signaling genes
and
. Our results indicate CBG as a phytocompound worth further investigation in the field of neuronal regeneration.
Background We compared the oncologic effectiveness of open adrenalectomy and endoscopic adrenalectomy in the treatment of patients with localized adrenocortical carcinoma. Methods One hundred ...fifty-six patients with localized adrenocortical carcinoma (stage I/II) who underwent R0 resection were included in an Italian multiinstitutional surgical survey. They were divided into 2 groups based on the operative approach (either conventional or endoscopic). Results One hundred twenty-six patients underwent open adrenalectomy and 30 patients underwent endoscopic adrenalectomy. The 2 groups were well matched for age, sex, lesion size, and stage ( P = NS). The mean follow-up time was similar for the 2 groups ( P = NS). The local recurrence rate was 19% for open adrenalectomy and 21% for endoscopic adrenalectomy, whereas distant metastases were recorded in 31% of patients in the conventional adrenalectomy group and 17% in the endoscopic adrenalectomy group ( P = NS). The mean time to recurrence was 27 ± 27 months in the conventional open adrenalectomy group and 29 ± 33 months in the endoscopic adrenalectomy group ( P = NS). No significant differences were found between the 2 groups in terms of 5-year disease-free survival (38.3% vs 58.2%) and 5-year overall survival rates (48% vs 67%; P = NS). Conclusion The operative approach does not affect the oncologic outcome of patients with localized adrenocortical carcinoma, if the principles of surgical oncology are respected.
Cannabis sativa L. proved to be a source of several phytocompounds able to help patients facing different diseases. Moreover, these phytocompounds can help ameliorate general conditions and control ...certain unpleasant effects of diseases. Some cannabinoids, however, provided more benefits applicable to settings other than palliative care. Using the NSC-34 cell line, we evaluated the barely known phytocompound named cannabinerol (CBNR) at different doses, in order to understand its unique characteristics and the ones shared with other cannabinoids. The transcriptomic analysis suggests a possible ongoing neuronal differentiation, principally due to the activation of cannabinoid receptor 1 (CB1), to which the phosphorylation of serine–threonine protein kinase (Akt) followed, especially between 20 and 7.5 µM. The increase of Neurod1 and Map2 genes at 7.5 µM, accompanied by a decrease of Vim, as well as the increase of Syp at all the other doses, point toward the initiation of differentiation signals. Our preliminary results indicate CBNR as a promising candidate to be added to the list of cannabinoids with neuronal differentiation-enhancer properties. However, further studies are needed to confirm this initial insight.
Background
With the increased diffusion of laparoscopic adrenalectomy (LA), surgeons from nonreferral surgical departments are beginning to approach this procedure, even if they are less experienced ...than surgeons from centers with a larger workflow. This study was designed to establish the real incidence of perioperative complications, in LA, in both major and minor surgical departments.
Methods
Patients were prospectively recorded into the Italian Registry of Endoscopic Surgery-Adrenalectomy (IRES-A) database since January 2000. Surgical Centers were divided in to referral centers (RC) with >30 adrenalectomies and nonreferral centers (NRC) with <30 adrenalectomies performed. Peri- and postoperative complications were evaluated.
Results
Of the 833 patients included in the IRES-A, 66 patients (7.9%) had complications (33 females; mean age 48 ± 8 years). Mean age and body mass index were significantly lower in noncomplicated patients. Pheochromocytoma histotype and large mass dimension were associated with a higher complication rate. The whole number of complications, conversion rate, and nonsurgery-related complications were statistically lower in the RC groups than the NRC groups.
Conclusions
The main risk factors for the occurrence of complications during laparoscopic adrenalectomy appear to be surgical inexperience, age, and body mass index of the patient, the dimension of the mass, and pheochromocytoma. Therefore, laparoscopic adrenalectomy, especially for tumors that are potentially more complicated, should only be undertaken in high-volume specialist centers by surgeons with the appropriate training and experience.
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