The Emerging Role of Neurosteroids: Novel Drugs Brexanalone, Sepranolone, Zuranolone, and Ganaxolone in Mood and Neurological Disorders.

This review investigates the potential of neurosteroids, including brexanolone, zuranolone, sepranolone, and ganaxalone, as therapeutic agents for a range of mood and neurological disorders. Notably, these disorders encompass postpartum depression, post-traumatic stress disorder (PTSD), major depressive disorder (MDD), epilepsy, and Alzheimer's disease. Brexanolone and zuranolone have emerged as frontrunners in the treatment of postpartum depression, offering rapid relief from debilitating symptoms. Their mechanism of action involves modulation of the gamma-aminobutyric acid (GABA) system, which plays a pivotal role in mood regulation. Clinical trials have demonstrated their efficacy, heralding a potential breakthrough in addressing this often-overlooked condition. In the context of PTSD and MDD, neurosteroids have demonstrated significant promise. Their positive allosteric modulation of GABA-A receptors translates into improved mood stabilization and reduced symptoms. This novel approach represents a departure from conventional treatments and could offer newfound hope for individuals grappling with these disorders. Beyond mood disorders, neurosteroids, especially ganaxalone, exhibit potential in the realm of epilepsy management. Ganaxalone's capacity to control seizures is attributed to its GABAergic activity, which helps restore the delicate balance of neurotransmission in epileptic brains. Moreover, neurosteroids have revealed neuroprotective properties in Alzheimer's disease models. By influencing the GABAergic system, they mitigate excitotoxicity, a hallmark of Alzheimer's pathology. This neuroprotection opens a novel avenue for slowing neurodegeneration, although further research and clinical validation are essential. In conclusion, this review underscores the substantial therapeutic promise of neurosteroids in mood and neurological disorders. Their modulation of the GABA system emerges as a central mechanism of action, emphasizing the importance of GABAergic signaling in these conditions. The path forward entails continued investigation and clinical trials to fully unlock the potential of neurosteroids, offering hope for enhanced treatments in these challenging clinical domains.

The Role of Diet and Gut Microbiome in Multiple Sclerosis.

Multiple sclerosis (MS) is a chronic demyelinating condition of the central nervous system (CNS) characterized by immune-mediated damage to the myelin sheath of nerve cells. Genetic and environmental factors are believed to play a significant role. Unfortunately, the knowledge of therapeutic modalities in MS remains very limited, necessitating the need for novel therapeutic strategies. In the previous decade, there has been an influx of studies on the gut microbiome and its link to various neurological conditions, including MS. Various diets may have favorable effects on the gut microflora and may significantly alter the progression and outcomes of MS. Thus, identifying the merits of various diets and modulating them according to the specific nutritional requirements of MS patients can go a long way toward slowing the progression of the disease. Nutritional interventions and the use of the gut microbiome as diagnostic and therapeutic modalities open a host of new possibilities regarding the disease. In this review, we investigate the role of diet and the gut microbiome in the progression of MS. The functions of the gut-brain axis, antioxidants, vitamins, obesity, and various diets are also covered in this article.

Central Retinal Artery Occlusion: Can We Effectively Manage This Ocular Emergency in a Hospital Setting?

Central retinal artery occlusion (CRAO) is an ophthalmological emergency characterized by partial or complete occlusion of the central retinal artery. It is the ocular equivalent of an ischemic cerebral stroke. Patients frequently present with a significant, abrupt, painless loss of vision in one eye, with only around 20% of those affected getting functional visual acuity restored in the affected eye. Despite more than 150 years of clinical research, no consensus has been achieved regarding the most effective method of treating CRAO. The efficacy of all proposed treatments is debatable, and many of them have ambiguous risk profiles that present particular diagnostic and management difficulties and cause variations in clinical practice. In certain circumstances, thrombolysis may be attempted as a treatment option. However, the evidence to support the general use of thrombolytics in treating acute CRAO remains elusive. It is known that the risk factors predisposing to other cardiovascular and cerebrovascular events are often present in CRAO. Accordingly, identifying patients at the highest risk of stroke and secondary prevention of ischemic events remains the primary focus of management. This review offers a summary of all the current treatment options available for managing CRAO, with particular reference to their limitations and inconsistent results found in relevant studies until 2022.

The Role of Mesenchymal Stem Cells in the Treatment of Type 1 Diabetes.

Type 1 diabetes (T1D) is a chronic disease characterized by inadequate or absent insulin production due to the autoimmune destruction of beta (ß) cells in the pancreas. It was once called "juvenile diabetes" since the disease frequently occurs in children, but it can also develop in adults. According to the International Diabetes Federation, an estimated 700 million adults will suffer from diabetes by 2045. Although the exact cause of diabetes remains unknown, it is hypothesized that genetic factors, environmental factors, and exposure to certain viruses play a role in the development of T1D. To date, exogenous insulin is the most common treatment for T1D. However, it is not a cure for the disease. Islet cell transplantation and pancreatic transplantation are two additional treatments that have gained popularity in recent years, but their clinical application may be limited by the need for high doses of immunosuppressants, the rarity of human cadaveric islets, and the need for extensive surgery in pancreatic transplantation. Mesenchymal stem cells (MSCs) are a highly promising novel treatment for T1D and their discovery has advanced biological sciences by allowing for modification of cell fate and the development of higher-order cellular structures. They play an essential role in lowering levels of fasting blood sugar, hemoglobin A1c, and C-peptide, and in treating microvascular complications associated with T1D. However, some of the disadvantages of its use in clinical practice are limited to its method of collection, proliferation rate, cell activity with age, and the risk of tumour formation identified in some studies. Large-scale studies are required to discover the mechanism of action of MSCs after administration as well as the optimal route, dose, and timing to maximize the benefits to patients. This article focuses primarily on the role of MSCs in the treatment of T1D and compares the feasibility, benefits, and drawbacks of MSCs in the treatment of T1D.

Therapeutic Efficacy of Botulinum Toxin in Trigeminal Neuralgia.

Trigeminal neuralgia (TN) is a unilateral, paroxysmal, sharp, shooting, or jabbing pain that occurs in the trigeminal nerve divisions, including the ophthalmic (V1), maxillary (V2), and mandibular (V3) nerves. Typically, an episode is triggered by anything touching the face or teeth. TN is a clinical diagnosis with no specific diagnostic test; it is determined by the patient's medical history and pain description. Imaging is necessary to exclude secondary causes. The precise reason for TN is uncertain, but it is commonly believed to result from vascular compression of the trigeminal nerve root, typically near its origin in the pons. There are numerous surgical and medical treatment options available. The most frequently applied medical treatment therapies are carbamazepine and oxcarbazepine. Surgical alternatives are reserved for patients who do not respond to medical treatment. Botulinum toxin A (BTX-A) has emerged as a novel and promising alternative to surgery for individuals whose pain is unresponsive to medication. Multiple studies have established the safety and usefulness of BTX-A in treating TN, with the most significant benefits occurring between six weeks and three months after the surgery. This article reviews various studies published in the last 10 years regarding the therapeutic use of BTX-A in TN. These studies include various observational, clinical, pilot, and animal studies.

Ethnical Disparities in Response to Edaravone in Patients With Amyotrophic Lateral Sclerosis.

Amyotrophic lateral sclerosis (ALS), also known as motor neuron disease (MND), is a progressive neurodegenerative disease characterized by the weakness of voluntary muscles due to the loss of motor neurons. Symptoms ultimately culminate in the form of respiratory failure due to the involvement of the diaphragm. Unfortunately, there is no known cure for this disease. Hence, supportive therapy is the only available option in most terminal cases. However, Riluzole and Edaravone (EDA) are the only two known drugs approved by the U.S. Food and Drug Administration (FDA) for treating this condition. In 2017, EDA was approved for the treatment of ALS. It is hypothesized that Riluzole and EDA work via a mechanism involving antioxidants, which nullifies the oxidative stress believed to be involved in ALS. However, most studies in several countries have found a wide range of disparities in the efficacy of this drug. In this review, we aim to summarize the differences in results from epidemiological studies across 10 different countries and hypothesize the potential causes of these differences.

Efficacy of subcutaneous interferon-beta in COVID-19: a meta-analysis and systematic review.

Type 1 interferons, especially interferon-beta, has been reported to be effective in COVID-19 patients in multiple randomized controlled trials. The aim of our meta-analysis and systematic review is to assess efficacy of subcutaneous IFN-beta in regards to mortality and discharge rate. Prospective, retrospective and randomized controlled trials were included. Primary outcomes measured were 28-day mortality and discharge rate. Secondary outcomes measured were mean hospital stay and post-intervention intubation rate. A thorough literature search was conducted in Medline, PubMed, Ovid journals, Google Scholar, and Cochrane Central Register of Controlled Trials & Database of Systematic Reviews from 1 April 2020 to 28 February 2021. Relative risk was calculated using both the Mantel-Haenszel method (fixed-effects model) and DerSimonian Laird method (random effects model). The heterogeneity among studies was tested using Cochran's Q test, based upon inverse variance weights. 7 studies were included in the meta-analysis and systematic review. The IFN-beta group did not improve the 28-day mortality (RR = 1.276; 95% CI: 1.106-1.472, p = 0.001) or the discharge rate (RR = 0.906; 95% CI = 0.85-0.95, p = < 0.001). The mean hospital stay was 11.95± 2.5 days in the interferon-beta group and 11.43 ± 3.74 days in the traditional treatment group. Likewise, interferon-beta did not add any advantage to post-intervention intubation rate (RR = 0.92; 95% CI = 0.7841-1.0816, p = 0.3154). Our findings revealed that use of subcutaneous interferon-beta is futile in COVID-19.