Volume 33, Issue 3

Major depressive disorder (MDD) is one of the most prevalent and debilitating psychiatric disorders, with a large number of patients not showing an effective therapeutic response to available treatments. Several biopsychosocial factors, such as stress in childhood and throughout life, and factors related to biological aging, may increase the susceptibility to MDD development. Included in critical biological processes related to aging and underlying biological mechanisms associated with MDD is the shortening of telomeres and changes in telomerase activity. This comprehensive review discusses studies that assessed the length of telomeres or telomerase activity and function in peripheral blood cells and brain tissues of MDD individuals. Also, results from in vitro protocols and animal models of stress and depressive-like behaviors were included. We also expand our discussion to include the role of telomere biology as it relates to other relevant biological mechanisms, such as the hypothalamic-pituitary-adrenal (HPA) axis, oxidative stress, inflammation, genetics, and epigenetic changes. In the text and the discussion, conflicting results in the literature were observed, especially considering the size of telomeres in the central nervous system, on which there are different protocols with divergent results in the literature. Finally, the context of this review is considering cell signaling, transcription factors, and neurotransmission, which are involved in MDD and can be underlying to senescence, telomere shortening, and telomerase functions.

The COVID-19 pandemic has affected millions of people worldwide. While coronaviruses typically have low rates of neurotropic effects, the massive transmission of SARS-CoV-2 suggests that a substantial population will suffer from potential SARS-CoV-2-related neurological disorders. The rapid and recent emergence of SARS-CoV-2 means little research exists on its potential neurological effects. Here we analyze the effects of similar viruses to provide insight into the potential effects of SARS-CoV-2 on the nervous system and beyond. Seven coronavirus strains (HCoV-OC43, HCoV-HKU1, HCoV-229E, HCoV-NL63, SARS-CoV, MERS-CoV, SARS-CoV-2) can infect humans. Many of these strains cause neurological effects, such as headaches, dizziness, strokes, seizures, and critical illness polyneuropathy/myopathy. Certain studies have also linked coronaviruses with multiple sclerosis and extensive central nervous system injuries. Reviewing these studies provides insight into the anticipated effects for patients with SARS-CoV-2. This review will first describe the effects of other coronaviruses that have caused severe disease (SARS-CoV, MERS-CoV) on the nervous system, as well as their proposed origins, non-neurological effects, and neurological infection mechanisms. It will then discuss what is known about SARS-CoV-2 in these areas with reference to the aforementioned viruses, with the goal of providing a holistic picture of SARS-CoV-2.

Stroke is a leading cause of death and disability worldwide. A common, chronic deficit after stroke is upper limb impairment, which can be exacerbated by compensatory use of the nonparetic limb. Resulting in learned nonuse of the paretic limb, compensatory reliance on the nonparetic limb can be discouraged with constraint-induced movement therapy (CIMT). CIMT is a rehabilitative strategy that may promote functional recovery of the paretic limb in both acute and chronic stroke patients through intensive practice of the paretic limb combined with binding, or otherwise preventing activation of, the nonparetic limb during daily living exercises. The neural mechanisms that support CIMT have been described in the lesioned hemisphere, but there is a less thorough understanding of the contralesional changes that support improved functional outcome following CIMT. Using both human and non-human animal studies, the current review explores the role of the contralesional hemisphere in functional recovery of stroke as it relates to CIMT. Current findings point to a need for a better understanding of the functional significance of contralesional changes, which may be determined by lesion size, location, and severity as well stroke chronicity.

The thermodynamic theory of action potential propagation challenges the conventional understanding of the nerve signal as an exclusively electrical phenomenon. Often misunderstood as to its basic tenets and predictions, the thermodynamic theory is virtually ignored in mainstream neuroscience. Addressing a broad audience of neuroscientists, we here attempt to stimulate interest in the theory. We do this by providing a concise overview of its background, discussion of its intimate connection to Albert Einstein’s treatment of the thermodynamics of interfaces and outlining its potential contribution to the building of a physical brain theory firmly grounded in first principles and the biophysical reality of individual nerve cells. As such, the paper does not attempt to advocate the superiority of the thermodynamic theory over any other approach to model the nerve impulse, but is meant as an open invitation to the neuroscience community to experimentally test the assumptions and predictions of the theory on their validity.

Polycythemia vera (PV) is a myeloproliferative disorder associated with an increased risk of cerebrovascular diseases. In this narrative review, we aimed to analyze the relationships between acute ischemic stroke and PV. We conducted a PubMed/Medline and Web of Sciences Database search using MeSH major terms. We found 75 articles and finally considered 12 case reports and 11 cohort studies. The ischemic stroke resulted as the first manifestation of PV in up to 16.2% of cases; the cumulative rate of cerebrovascular events was up to 5.5 per 100 persons per year and stroke accounted for 8.8% of all PV-related deaths; age, mutations, and a previous history of thrombosis were the main risk factors. The best approach to reduce stroke recurrence risk is unclear, even if some evidence suggests a potential role of lowering hematocrit below 45%. Ischemic stroke represents one of the most common PV manifestations but, despite their relationship, patients with both diseases have a very heterogeneous clinical course and management. PV-related strokes often remain underdiagnosed, especially for the low prevalence of PV. An early diagnosis could lead to prompt treatment with phlebotomy, cytoreduction, and low-dose aspirin to decrease the risk of recurrences. Clinicians should be aware of PV as a risk factor for stroke when approaching the differential diagnosis of cryptogenic strokes. An early diagnosis could positively influence patients’ management and clinical outcomes. Further studies are required to evaluate the role of PV treatments in the prevention of cerebrovascular disease.

Glioblastoma remains lethal even when treated with standard therapy. This review aims to outline the recent development of various advanced therapeutics for glioblastoma and briefly discuss the potential impact of glioblastoma and some of its therapeutic approaches on the neurological function micturition control. Although immunotherapy led to success in treating hematological malignancies, but no similar success occurred in treatment for brain glioblastoma. Neither regenerative medicine nor stem cell therapy led to astounding success in glioblastoma. However, CRISPR Cas system holds potential in multiple applications due to its capacity to knock-in and knock-out genes, modify immune cells and cell receptors, which will enable it to address clinical challenges in immunotherapy such as CAR-T and regenerative therapy for brain glioblastoma, improving the precision and safety of these approaches. The studies mentioned in this review could indicate that glioblastoma is a malignant disease with multiple sophisticated barriers to be overcome and more challenges might arise in the attempt of researchers to yield a successful cure. A multimodal approach of future generation of refined and safe therapeutics derived from CRISPR Cas therapeutics, immunotherapy, and regenerative therapeutics mentioned in this review might prolong survival or even contribute towards a potential cure for glioblastoma.

Traumatic brain injury (TBI) is a major cause of mortality and morbidity, affecting 2 million people annually in the US alone, with direct and indirect costs of $76.3 billion per year. TBI is a progressive disease with no FDA-approved drug for treating patients. Early, accurate and rapid diagnosis can have significant implications for successful triaging and intervention. Unfortunately, current clinical tests for TBI rely on CT scans and MRIs, both of which are expensive, time-consuming, and not accessible to everyone. Recent evidence of biofluid-based biomarkers being released right after a TBI incident has ignited interest in developing point-of-care (POC) platforms for early and on-site TBI diagnosis. These efforts face many challenges to accurate, sensitive, and specific diagnosis and monitoring of TBI. This review includes a deep dive into the latest advances in chemical, mechanical, electrical, and optical sensing systems that hold promise for TBI-POC diagnostic testing platforms. It also focuses on the performance of these proposed biosensors compared to biofluid-based orthodox diagnostic techniques in terms of sensitivity, specificity, and limits of detection. Finally, it examines commercialized TBI-POCs present in the market, the challenges associated with them, and the future directions and prospects of these technologies and the field.