Aging is a multifactorial biological process characterized by the progressive decline of cellular, tissue, and organ functions, leading to increased vulnerability to neurodegenerative disorders. Among the proposed mechanisms, the oxidative stress theory of aging remains one of the most widely accepted, emphasizing the role of reactive oxygen species (ROS) accumulation, particularly in the central nervous system (CNS). Mercury is a persistent environmental pollutant known to induce oxidative damage, but its contribution to age-related neuronal decline remains poorly understood. Our aim of this study was to investigate whether chronic HgCl2 exposure exacerbates age-related decline in memory and locomotor functions in aged male mice. To this end, mice were divided into two groups: A control group, which received only tap water, and an HgCl2-exposed group, which received 40 ppm HgCl2 in their drinking water daily from gestation until 18 months of age. At the end of the exposure, mice were subjected to behavioral tests to assess memory and locomotor activity. Following these behavioral assessments, oxidative stress parameters and acetylcholinesterase (AChE) activity were measured in the hippocampus and cerebellum. Our results showed that HgCl2 impaired locomotor activity in the Open Field test (OF) and memory performance in the Y-maze and Novel Object Recognition (NOR) test. These deficits were accompanied by a significant increase in malondialdehyde (MDA) and acetylcholinesterase (AChE) activity in the hippocampus. Furthermore, mercury exposure led to an increase in MDA and a significant upregulation of catalase (CAT) and superoxide dismutase (SOD) activities in the cerebellum. These changes were also associated with a marked decrease in AChE activity within the same region. Overall, these findings suggest that lifelong mercury exposure accelerates neurobehavioral decline by exacerbating oxidative and cholinergic disturbances, providing insight into how early and sustained exposure to environmental toxicants may promote premature brain aging.

Repetitive transcranial magnetic stimulation (rTMS) is a promising adjunct in stroke rehabilitation, with increasing focus on the supplementary motor area (SMA) for its role in motor and language network reorganization. This systematic review evaluated randomized controlled trials (RCTs) assessing rTMS targeting the SMA or modulating its connectivity to improve motor and language outcomes in adults after ischemic or hemorrhagic stroke. A comprehensive literature search was performed across PubMed, Web of Science, and Google Scholar, focusing on peer-reviewed RCTs published in English. Studies were eligible if they involved adults with stroke at any recovery stage and assessed rTMS targeting or analyzing the SMA. Two independent reviewers screened records, extracted data, and assessed risk of bias using the Cochrane Risk of Bias 2.0 tool. The review adhered to PRISMA guidelines and was registered in PROSPERO (CRD420251051684). Among 74 screened for full text, five RCTs were included. Across studies, rTMS interventions targeting the SMA or modulating SMA-related networks improved motor and language outcomes in stroke patients. Neuroimaging measures consistently demonstrated increased SMA activation and strengthened SMA-primary motor cortex (M1) connectivity after rTMS, which correlated with clinical improvements. Balance and postural control outcomes showed the most consistent benefits, while upper-limb motor and language improvements varied in magnitude and follow-up duration. Heterogeneity in studies, small sample sizes, and concerns about randomization and reporting limit our ability to draw definitive conclusions. SMA-targeted or network-level rTMS appears to facilitate functional recovery after stroke, supported by neuroimaging evidence of brain network reorganization. Further large, standardized RCTs are necessary to establish optimal protocols, confirm efficacy, and assess long-term outcomes.

Neurons are especially vulnerable because of their high metabolic activity and limited ability to repair damaged DNA. Oxidative genotoxic stress (OGS), which arises from the buildup of short-lived, highly reactive molecules called reactive oxygen species (ROS), can damage neuronal DNA and compromise antioxidant defense mechanisms in neurons. OGS induces considerable forms of DNA damage, including genomic instability, DNA strand breaks (single or double), DNA base modifications such as 8-oxoguanine, and epigenetic changes, leading to compromised neuronal functions. Moreover, OGS is a silent player in mitochondrial DNA damage and mitochondrial dysfunction. Therefore, ROS-mediated OGS is pivotal for initiating and advancing several neurodegenerative diseases, such as Alzheimer's disease (AD), Parkinsonism (PD), and Huntington's disease (HD). However, there is a significant gap in deciphering the molecular pathways involved in OGS-mediated development of neurodegenerative diseases. Hence, this study focused on the molecular mechanisms by which OGS causes neurodegeneration, with a focus on the contributions of neuroinflammation, mitochondrial dysfunction, and defective DNA repair pathways. Additionally, new therapeutic approaches, such as mitochondrial-targeted medications, antioxidant therapies, gene editing tools such as CRISPR/Cas9, and biomarkers for the early diagnosis of these oxidative diseases, have been assessed. A thorough comprehension of these processes opens exciting possibilities for focused treatments in neurodegenerative illnesses.

Parkinson's disease (PD) is characterized by the pathological accumulation of α-synuclein, which has driven extensive research into the role of exosomes in disease mechanisms. Exosomes are nanoscale vesicles enriched with proteins, RNA, and lipids that facilitate critical intercellular communication processes. Recent studies have elucidated the role of exosomes in transmitting misfolded proteins among neurons, which significantly impacts the progression of PD. The presence of disease-associated exosomes in cerebrospinal fluid and blood highlights their substantial diagnostic potential for PD. Specifically, exosomes derived from the central nervous system (CNS) have emerged as promising biomarkers because of their ability to accurately reflect pathological states. Furthermore, the isolation of exosomes from distinct brain cell types allows the identification of precise biomarkers, increasing diagnostic specificity and accuracy. In addition to being useful for diagnostics, exosomes hold therapeutic promise given their ability to cross the blood-brain barrier (BBB) and selectively modulate their cargo. These findings suggest that these materials could be used as delivery systems for therapeutic drugs for the treatment of neurodegenerative diseases. This review comprehensively examines the multifaceted roles of exosomes in PD pathogenesis, diagnosis, and treatment. It also addresses the associated clinical challenges and underscores the urgent need for further research and development to fully leverage exosome-based strategies in PD management.

Pain is an essential aspect of the body's physiological response to unpleasant noxious stimuli from either external sustained injuries or an internal disease condition that occurs within the body. Generally, pain is temporary. However, in patients with neuropathic pain, the experienced pain is persistent and uncontrollable, with an unsatisfactory treatment effectiveness. The activation of the immune system is a crucial factor in both central and peripheral neuropathic pain. The immune response plays an important role in the progression of the stages of neuropathic pain, and acts not only as pain mediators, but also produce analgesic molecules. Neuropathic pain has long been described as a result of dysfunctional nerve activities. However, there is substantial evidence indicating that the regulation of hyperalgesia is mediated by astrocytes and microglia activation. Mesenchymal stem cells currently hold an optimal potential in managing pain, as they can migrate to damaged tissues and have a robust immunosuppressive role for autologous or heterologous transplantation. Moreover, mesenchymal stem cells revealed their immunomodulatory capabilities by secreting growth factors and cytokines through direct cell interactions. The main idea underlying the use of mesenchymal stem cells in pain management is that these cells can replace damaged nerve cells by releasing neurotrophic factors. This property makes them the perfect option to modulate and treat neuropathic pain, which is notoriously difficult to treat.

It is rare to find free floating fat droplets in the cerebral spinal fluid (CSF) spaces of the brain. When fat droplets are seen in the CSF spaces, the most common cause is the rupture of a dermoid cyst. Dermoid cysts are congenital inclusion cysts that form during the neural tube closure between the third and fifth weeks of embryogenesis. In this case report, we describe a case of a 74-year-old, right-handed female who presented with an acute onset of visual disturbances and left-hand numbness. Computed tomography (CT) and magnetic resonance imaging (MRI) of the head revealed hypodense "lesions" in the lateral ventricles and basal cisterns. The CT Hounsfield unit was between -41 to -83 Hounsfield Units, which is compatible with fat rather than air. The T1 weighted and FLAIR MRI showed hyperintense lesions "floating" on top of the CSF in the lateral ventricles, which is typical for fat droplets, presumably caused by a ruptured dermoid cyst. This case emphasizes the importance of analyzing Hounsfield Units to distinguish lesions by density, where fat ranges from -50 to -150 Hounsfield Units and air is -1000 Hounsfield Units. Pneumocephalus is the presence of air in the epidural, subdural, or subarachnoid space and can cause confusion, nausea, seizures and focal neurological symptoms. A careful analysis of the neuroimaging findings in the CT with or without MRI is important in making a correct diagnosis of a ruptured dermoid cyst versus pneumocephalus.

Spinal cord injury (SCI) is a debilitating condition that results in impaired sensory and motor function due to the limited self-regenerative ability of the spinal cord. To address this issue, combination therapy has been proposed as an effective treatment strategy for SCI regeneration. In this study, Platelet-Rich Plasma (PRP)-derived exosomes loaded with dexamethasone were utilized in a mouse model of SCI compression. PRP-derived exosomes loaded with dexamethasone (Dex) were prepared using ultracentrifugation and sonication methods and were administered to the mice via intravenous injection. Following a four-week duration, behavioral assessments were administered to assess functional recuperation, and diverse metrics encompassing the expression of genes associated with apoptosis and antiapoptosis, serum cytokine concentrations and tissue sampling were subjected to thorough examination. The results of this study demonstrated that mice treated with PRP-derived exosomes loaded with Dex (ExoDex) exhibited altered levels of TNF-α and IL-10, along with decreased Bax and increased Bcl2 expression in comparison to the model group. Furthermore, intravenously injected ExoDex reduced the size of the lesion site, lymphocyte infiltration, vacuolation, cavity size and tissue disorganization while also improving locomotor recovery. We propose that the utilization of exosome-loaded Dex therapy holds potential as a promising and clinically relevant approach for injured spinal cord repair. However, further extensive research is warranted in this domain to validate and substantiate the outcomes presented in this study.

<abstract> <p>Whole Body Vibration has been found to induce physiological changes in human subjects, improving their neuromuscular, respiratory and cardiovascular functions. Evidence from animal research prove that whole-body vibration appears to induce changes in molecular and cellular levels to alter cognitive functions in mice. There is evolving evidence for a potential value of whole body vibration in improving cognition and preventing the development of age-related cognitive disorders in humans. However, literature on the biological consequences of whole-body vibration on the human brain is scanty. If so, gathering the available evidences would help decide the possibility of designing appropriate whole-body vibration protocols to extend its application to induce neurocognitive enhancement and optimize its effects. Therefore, a systematic review of the literature was performed, consulting the ProQuest, MEDLINE and Scopus bibliographic databases, to summarize the available scientific evidence on the effects of whole-body vibration on cognitive functions in adults. Results of the review suggest that whole-body vibration therapy enhances a wide spectrum of cognitive functions in adults although there isn't enough evidence available yet to be able to design a standardized protocol to achieve optimum cognitive enhancement.</p> </abstract>

This literature review explores the pivotal roles of the Uncoordinated-13 (UNC13) protein family, encompassing UNC13A, UNC13B, UNC13C, and UNC13D, in the pathogenesis of various human diseases. These proteins, which are evolutionarily conserved and crucial for synaptic vesicle priming and exocytosis, have been implicated in a range of disorders, spanning from neurodegenerative diseases like amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) to immune-related conditions such as familial hemophagocytic lymphohistiocytosis (FHL). The involvement of UNC13A in neurotransmitter release and synaptic plasticity is linked to ALS and FTD, with genetic variations affecting disease progression. UNC13B, which is closely related to UNC13A, plays a role in autism spectrum disorders (ASD), epilepsy, and schizophrenia. UNC13C is implicated in oral squamous cell carcinoma (OSCC) and hepatocellular carcinoma (HCC), and has a neuroprotective role in Alzheimer's disease (AD). UNC13D has an essential role in immune cell function, making it a key player in FHL. This review highlights the distinct molecular functions of each UNC13 family member and their implications in disease contexts, shedding light on potential therapeutic strategies and avenues for future research. Understanding these proteins' roles offers new insights into the management and treatment of neurological and immunological disorders.