Volume 32, Issue 2

Early life stress (ELS) is one of the most critical factors that could modify brain plasticity, memory and learning abilities, behavioral reactions, and emotional response in adulthood leading to development of different mental disorders. Prenatal and early postnatal periods appear to be the most sensitive periods of brain development in mammals, thereby action of various factors at these stages of brain development might result in neurodegeneration, memory impairment, and mood disorders at later periods of life. Deciphering the processes underlying aberrant neurogenesis, synaptogenesis, and cerebral angiogenesis as well as deeper understanding the effects of ELS on brain development will provide novel approaches to prevent or to cure psychiatric and neurological deficits caused by stressful conditions at the earliest stages of ontogenesis. Neuropeptide oxytocin serves as an amnesic, anti-stress, pro-angiogenic, and neurogenesis-controlling molecule contributing to dramatic changes in brain plasticity in ELS. In the current review, we summarize recent data on molecular mechanisms of ELS-driven changes in brain plasticity with the particular focus on oxytocin-mediated effects on neurogenesis and angiogenesis, memory establishment, and forgetting.

The gut microbiota plays an important role in neurological diseases via the gut–brain axis. Many factors such as diet, antibiotic therapy, stress, metabolism, age, geography and genetics are known to play a critical role in regulating the colonization pattern of the microbiota. Recent studies have shown the role of the low carbohydrate, adequate protein, and high fat “ketogenic diet” in remodeling the composition of the gut microbiome and thereby facilitating protective effects in various central nervous system (CNS) disorders. Gut microbes are found to be involved in the pathogenesis of various CNS disorders like epilepsy, Parkinson’s disease (PD), Alzheimer’s disease (AD), autism spectrum disorders (ASDs), multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS) and stress, anxiety and depression. In vivo studies have shown an intricate link between gut microbes and KD and specific microbes/probiotics proved useful in in vivo CNS disease models. In the present review, we discuss the gut–brain bidirectional axis and the underlying mechanism of KD-based therapy targeting gut microbiome in in vivo animal models and clinical studies in neurological diseases. Also, we tried to infer how KD by altering the microbiota composition contributes towards the protective role in various CNS disorders. This review helps to uncover the mechanisms that are utilized by the KD and gut microbiota to modulate gut–brain axis functions and may provide novel opportunities to target therapies to the gut to treat neurologic disorders.

Genes associated with parkinsonism may also be implicated in carcinogenesis, but their interplay remains unclear. We systematically reviewed studies (PubMed 1967–2019) reporting gene variants associated with both parkinsonism and cancer. Somatic variants were examined in cancer samples, whereas germline variants were examined in cancer patients with both symptomatic and asymptomatic (carriers) genetic parkinsonisms. Pooled proportions were calculated with random-effects meta-analyses. Out of 9,967 eligible articles, 60 were included. Of the 28 genetic variants associated with parkinsonism, six were also associated with cancer. In cancer samples, SNCA was predominantly associated with gastrointestinal cancers , UCHL1 with breast cancer, and PRKN with head-and-neck cancers. In asymptomatic carriers, LRRK2 was predominantly associated with gastrointestinal and prostate cancers, PRKN with prostate and genitourinary tract cancers, GBA with sarcoma, and 22q11.2 deletion with leukemia. In symptomatic genetic parkinsonism, LRRK2 was associated with nonmelanoma skin cancers and breast cancers, and PRKN with head-and-neck cancers. Cancer was more often manifested in genetic parkinsonisms compared to asymptomatic carriers. These results suggest that intraindividual genetic contributions may modify the co-occurrence of cancer and neurodegeneration.

Spinal injury is among the most severe and feared injuries an athlete may face. We present an up-to-date review of the recent literature, stratifying recommendations based on injury location (cervical, thoracic, and lumbar spine) and type, as well as, the level of competitive play (high school, collegiate, professional). A literature search was completed to identify all publications reporting return to play guidelines for athletic injuries or injury-related surgery irrespective of the study design. Publication dates were not restricted by year. Search terms used included “return to play” and “spinal injury” on National Library of Medicine (PubMed) and Google Scholar. Selection criteria for literature included axial spine injury guidelines for athletic participation post-injury or post-surgery. Literature found from the search criteria was sorted based on level of competition and location of axial spine injury involved. It was found that professional athletes are more likely to suffer severe spinal injuries, require surgery, and necessitate a longer return to play (RTP), with high school and college athletes usually returning to play within days or weeks. Injuries occur mainly within contact sports and concordance exists between initial and subsequent spinal injuries. Adequate rest, rehabilitation, and protective equipment alongside the education of athletes and coaches are recommended. In conclusion, a multidisciplinary approach to patient management is required with consideration for the emotional, social, and perhaps financial impact that spinal injury may have upon the athlete. Consensus from the literature states that in order for an athlete to safely return to play, that athlete should not be actively suffering from pain, should have a full range of motion, and complete return of their strength in the absence of neurological deficit.

Brief maneuvering of the literature as to the various roles attributed to the basal ganglia corticostriatal circuits in a variety of cognitive processes such as working memory, selective attention, and category learning has inspired us to investigate the interplay of the two major basal ganglia open-recurrent loops, namely, visual and executive loops specifically the possible involvement of their overlap in conditional learning. We propose that the interaction of the visual and executive loops reflected through their cortical overlap in the dorsolateral prefrontal cortex (DL-PFC), lateral orbitofrontal cortex (LO-PFC), and presupplementary motor area (SMA) plays an instrumental role preliminary first in forming associations between a series of correct responses following similar stimuli and then in shifting, abstracting, and generalizing conditioned responses. The premotor and supplementary motor areas have been shown essential to producing a sequence of movements while the SMA is engaged in monitoring complex movements. In light of the recent studies, we will suggest that the interaction of visual and executive loops could strengthen or weaken learned associations following different reward values. Furthermore, we speculate that the overlap of the visual and executive loops can account for the switching between the associative vs. rule-based category learning systems.

Vascular endothelial growth factor (VEGF) has a crucial role in the angiogenesis of various tumors, including glioma. As the levels of VEGF would change in patients with glioma, we conducted the current systematic review and meta-analysis to more clearly determine the VEGF level alterations in different grades of glioma. PubMed and Scopus databases were sensitively searched for all the possible keywords addressing glioma and VEGF. Case–control and cohort studies on human subjects, which measured VEGF levels were eligible to be included in the study. Out of a total number of 3,612 studies, 22 studies were included and 12 studies entered the meta-analysis. This review revealed that serum levels of VEGF in glioma patients were 1.56 pg/dL higher compared to healthy controls ( P  = 0.05). Besides, immunohistochemistry (IHC) measurement of VEGF in surgical biopsies indicated significant difference in these two groups as well ( P  = 0.02). Yet, there was not a significant difference between patients with low-grade gliomas (World Health Organization (WHO) grades I-II, LGG) and those with high-grade gliomas (WHO grades III-IV, HGG) ( P  = 0.43). The results of this systematic review and meta-analysis demonstrate that VEGF levels would significantly increase in glioma, and therefore, could be potentially considered as a biomarker for this cancer.

Mitochondrial activity is essential to support neural functions, and changes in the integrity and activity of the mitochondria can contribute to synaptic damage and neuronal death, especially in degenerative diseases associated with age, such as Alzheimer’s and Parkinson’s disease. Currently, different approaches are used to treat these conditions, and one strategy under research is mitochondrial transplantation. For years, mitochondria have been shown to be transferred between cells of different tissues. This process has allowed several attempts to develop transplantation schemes by isolating functional mitochondria and introducing them into damaged tissue in particular to counteract the harmful effects of myocardial ischemia. Recently, mitochondrial transfer between brain cells has also been reported, and thus, mitochondrial transplantation for disorders of the nervous system has begun to be investigated. In this review, we focus on the relevance of mitochondria in the nervous system, as well as some mitochondrial alterations that occur in neurodegenerative diseases associated with age. In addition, we describe studies that have performed mitochondrial transplantation in various tissues, and we emphasize the advances in mitochondrial transplantation aimed at treating diseases of the nervous system.

COVID-19 was first reported in December 2019 in the Wuhan city of China, and since then it has spread worldwide taking a heavy toll on human life and economy. COVID-19 infection is commonly associated with symptoms like coughing, fever, and shortness of breath, besides, the reports of muscle pain, anosmia, hyposmia, and loss of taste are becoming evident. Recent reports suggest the pathogenic invasion of the SARS-CoV-2 into the CNS, that could thereby result in devastating long term complications, primarily because some of these complications may go unnoticed for a long time. Evidence suggest that the virus could enter the CNS through angiotensin-converting enzyme-2 (ACE-2) receptor, neuronal transport, haematogenous route, and nasal route via olfactory bulb, cribriform plate, and propagates through trans-synaptic signalling, and shows retrograde movement into the CNS along nerve fiber. COVID-19 induces CNS inflammation and neurological degenerative damage through a diverse mechanism which includes ACE-2 receptor damage, cytokine-associated injury or cytokine storm syndrome, secondary hypoxia, demyelination, blood–brain barrier disruption, neurodegeneration, and neuroinflammation. Viral invasion into the CNS has been reported to show association with complications like Parkinsonism, Alzheimer’s disorder, meningitis, encephalopathy, anosmia, hyposmia, anxiety, depression, psychiatric symptoms, seizures, stroke, etc. This review provides a detailed discussion of the CNS pathogenesis of COVID-19. Authors conclude that the COVID-19 cannot just be considered as a disorder of the pulmonary or peripheral system, rather it has a significant CNS involvement. Therefore, CNS aspects of the COVID-19 should be monitored very closely to prevent long term CNS complications, even after the patient has recovered from COVID-19.

The coronavirus disease (COVID-19), identified in Wuhan, China, on December 2019, was declared a pandemic by the World Health Organization, on March, 2020. Since then, efforts have been gathered to describe its clinical course and to determine preventive measures and treatment strategies. Adults older than 65 years of age are more susceptible to serious clinical symptoms and present higher mortality rates. Angiotensin-converting enzyme 2 (ACE2) is a major receptor for some coronavirus infection, including SARS-COV-2, but is also a crucial determinant in anti-inflammation processes during the renin–angiotensin system (RAS) functioning – converting angiotensin II to angiotensin 1–7. The decline in ACE2 expression that occurs with aging has been associated to the higher morbidity and mortality rates in older adults. These observations highlight the importance of investigating the association between COVID-19 and age-related neurodegenerative disorders, i.e., Parkinson’s and Alzheimer’s diseases. A possible option to reduce the risk of COVID-19 is vitamin D supplementation, due to its anti-inflammatory and immune-system-modulating effects. It has also been suggested that vitamin D supplementation plays a role in slowing progression of Parkinson and Alzheimer. The present study is a literature review of articles published on the theme COVID-19, Parkinson and Alzheimer’s diseases, and the role played by vitamin D. PUBMED, MEDLINE, and EMBASE databases were consulted. Results confirm neurodegenerative and neuroinflammatory effects of COVID-19, aggravated in Parkinson’s and Alzheimer’s patients, and the important role of vitamin D as a possible therapeutic strategy. Nevertheless, randomized controlled trials and large population studies are still warranted.