Mortality Predictors for Adult Patients with Mild-to-Moderate Traumatic Brain Injury: A Literature Review.

Traumatic brain injuries (TBIs) represent a significant public health concern, with mild-to-moderate cases comprising a substantial portion of incidents. Understanding the predictors of mortality among adult patients with mild-to-moderate TBIs is crucial for optimizing clinical management and improving outcomes. This literature review examines the existing research to identify and analyze the mortality predictors in this patient population. Through a comprehensive review of peer-reviewed articles and clinical studies, key prognostic factors, such as age, Glasgow Coma Scale (GCS) score, the presence of intracranial hemorrhage, pupillary reactivity, and coexisting medical conditions, are explored. Additionally, this review investigates the role of advanced imaging modalities, biomarkers, and scoring systems in predicting mortality following a mild-to-moderate TBI. By synthesizing the findings from diverse studies, this review aims to provide clinicians and researchers with valuable insights into the factors influencing mortality outcomes in adult patients with a mild-to-moderate TBI, thus facilitating more informed decision making and targeted interventions in clinical practice.

Management of Phantom Limb Pain through Thalamotomy of the Centro-Median Nucleus.

BACKGROUND: Phantom limb syndrome is defined as the perception of intense pain or other sensations that are secondary to a neural lesion in a limb that does not exist. It can be treated using pharmacological and surgical interventions. Most medications are prescribed to improve patients' lives; however, the response rate is low. In this case report, we present a case of phantom limb syndrome in a 42-year-old female with a history of transradial amputation of the left thoracic limb due to an accidental compression one year before. The patient underwent placement of a deep brain stimulator at the ventral posteromedial nucleus (VPM) on the right side and removal secondary to loss of battery. The patient continued to have a burning pain throughout the limb with a sensation of still having the limb, which was subsequently diagnosed as phantom limb syndrome. After a thorough discussion with the patient, a right stereotactic centro-median thalamotomy was offered. An immediate response was reported with a reduction in pain severity on the visual analogue scale (VAS) from a value of 9-10 preoperative to a value of 2 postoperative, with no postoperative complications. Although phantom limb pain is one of the most difficult to treat conditions, centro-median thalamotomy may provide an effective stereotactic treatment procedure with adequate outcomes.

Housing R6/2 Mice with Wild-Type Littermates Increases Lifespan.

The R6/2 murine model of Huntington's disease (HD) is extensively used in HD research. The current study replicates and extends previous work assessing the impact of housing R6/2 mice with healthy wild-type (WT) littermates on disease progression. The current study extends the previous finding by including male cohorts and the use of a standard diet and water regimen, as opposed to the enhanced diet used in the previous study. This study found that the inclusion of healthy wild-type (WT) littermates, alone, improved survivabilty in R6/2 mice, but did not have a significant impact on weight loss.

Pharmacological Approaches in Neurofibromatosis Type 1-Associated Nervous System Tumors.

Neurofibromatosis type 1 is an autosomal dominant genetic disease and a common tumor predisposition syndrome that affects 1 in 3000 to 4000 patients in the USA. Although studies have been conducted to better understand and manage this disease, the underlying pathogenesis of neurofibromatosis type 1 has not been completely elucidated, and this disease is still associated with significant morbidity and mortality. Treatment options are limited to surgery with chemotherapy for tumors in cases of malignant transformation. In this review, we summarize the advances in the development of targeted pharmacological interventions for neurofibromatosis type 1 and related conditions.

Twenty Years After Glioblastoma Multiforme Diagnosis: A Case of Long-Term Survival.

Glioblastoma multiforme (GBM) is an aggressive tumor that has a poor prognosis with a median survival of 15 months with treatment and 3-4 months without treatment. Subsets of patients are found to survive longer than two years, some survivors lived more than 10 years, and rare cases survived 20 years or more with treatment. Better prognosis has been found to be associated with many factors. Some of these factors are related to patients' characteristics, biological factors that impact tumor aggressiveness, and/or factors associated with treatment. However, the exact contribution for extended survival is still not known. Finding the factors that have a strong impact on the long survival is of high importance and can help give hope to better treat glioblastoma cases. In this report, we present a case of a glioblastoma patient who was diagnosed at the age of 47 years with more than 20-year survival. We further discuss the suggested factors that may have contributed to a better prognosis with a focus on the possible role of varicella-zoster infection in mediating long-term survival.

Acute and Post-Acute Neurological Complications of COVID-19.

Coronavirus disease 2019 (COVID-19) is an emerging global health emergency caused by the novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The global outbreak of SARS-CoV-2 infection has been declared a global pandemic by the World Health Organization (WHO). The clinical presentation of SARS-CoV-2 infection depends on the severity of the disease and may range from an asymptomatic infection to a severe and lethal illness. Fever, cough, and shortness of breath are among the most common symptoms associated with SARS-CoV-2 infection. Accumulating evidence indicates that COVID-19 patients commonly develop neurological symptoms, such as headache, altered mental status, anosmia, and myalgia. In this comprehensive literature review, we have summarized the most common neurological complications and reported neurological case studies associated with COVID-19, and neurological side effects associated with COVID-19 treatments. Additionally, the post-acute COVID-19 syndrome and long-term neurological complications were discussed. We also explained the proposed mechanisms that are involved in the pathogenesis of these neurological complications.

Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)1.

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field.

Liraglutide Has Anti-Inflammatory and Anti-Amyloid Properties in Streptozotocin-Induced and 5xFAD Mouse Models of Alzheimer's Disease.

Recent clinical and epidemiological studies support the contention that diabetes mellitus (DM) is a strong risk factor for the development of Alzheimer's disease (AD). The use of insulin cell toxin, streptozotocin (STZ), when injected into the lateral ventricles, develops an insulin resistant brain state (IRBS) and represents a non-transgenic, or sporadic AD model (SAD), with several AD-like neuropathological features. The present study explored the effects of an anti-diabetic drug, liraglutide (LIR), in reversing major pathological hallmarks in the prodromal disease stage of both the 5xFAD transgenic and SAD mouse models of AD. Three-month-old 5xFAD and age-matched wild type mice were given a single intracerebroventricular (i.c.v) injection of STZ or vehicle (saline) and were subsequently treated with LIR, intraperitoneally (IP), once a day for 30 days. The extent of neurodegeneration, Aß plaque load, and key proteins associated with the insulin signaling pathways were measured using Western blot and neuroinflammation (via immunohistological assays) in the cortical and hippocampal regions of the brain were assessed following a series of behavioral tests used to measure cognitive function after LIR or vehicle treatments. Our results indicated that STZ significantly increased neuroinflammation, Aß plaque deposition and disrupted insulin signaling pathway, while 25 nmol/kg LIR, when injected IP, significantly decreased neuroinflammatory responses in both SAD and 5xFAD mice before significant cognitive changes were observed, suggesting LIR can reduce early neuropathology markers prior to the emergence of overt memory deficits. Our results indicate that LIR has neuroprotective effects and has the potential to serve as an anti-inflammatory and anti-amyloid prophylactic therapy in the prodromal stages of AD.

Reducing Spread of Infections with a Photocatalytic Reactor-Potential Applications in Control of Hospital Staphylococcus aureus and Clostridioides difficile Infections and Inactivation of RNA Viruses.

Contaminated surfaces and indoor environments are important sources of infectious spread within hospital and non-hospital facilities. Bacterial infections such as infections with Clostridioides (formerly Clostridium) difficile (C. difficile) and Staphylococcus aureus (S. aureus) and its antibiotic resistant strains continue to pose a significant risk to healthcare workers and patients. Additionally, the recent emergence of the coronavirus disease 2019 (COVID-19) pandemic, which is caused by the novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), highlights the need for safe and effective methods to decontaminate surfaces to control infection spread in hospitals and the community. To address these critical needs, we tested a photocatalytic reactor decontamination method to disinfect contaminated surfaces in a hospital and a laboratory setting. By placing the reactor in a test hospital room, growth of S. aureus and C. difficile were significantly reduced compared with a control room. Additionally, using a model enveloped positive-sense single-stranded RNA virus, dengue virus type 2 (DENV2), we showed that the use of the photocatalytic reactor reduces viral infectivity. Collectively, the results demonstrate the potential utility of photocatalytic reactors in reducing the spread of highly contagious bacterial and viral infections through contaminated surfaces and environments.

Solid Lipid Curcumin Particles Protect Medium Spiny Neuronal Morphology, and Reduce Learning and Memory Deficits in the YAC128 Mouse Model of Huntington's Disease.

Huntington's disease (HD) is a genetic neurodegenerative disorder characterized by motor, cognitive, and psychiatric symptoms, accompanied by massive neuronal degeneration in the striatum. In this study, we utilized solid lipid curcumin particles (SLCPs) and solid lipid particles (SLPs) to test their efficacy in reducing deficits in YAC128 HD mice. Eleven-month-old YAC128 male and female mice were treated orally with SLCPs (100 mg/kg) or equivalent volumes of SLPs or vehicle (phosphate-buffered saline) every other day for eight weeks. Learning and memory performance was assessed using an active-avoidance task on week eight. The mice were euthanized, and their brains were processed using Golgi-Cox staining to study the morphology of medium spiny neurons (MSNs) and Western blots to quantify amounts of DARPP-32, brain-derived neurotrophic factor (BDNF), TrkB, synaptophysin, and PSD-95. We found that both SLCPs and SLPs improved learning and memory in HD mice, as measured by the active avoidance task. We also found that SLCP and SLP treatments preserved MSNs arborization and spinal density and modulated synaptic proteins. Our study shows that SLCPs, as well as the lipid particles, can have therapeutic effects in old YAC128 HD mice in terms of recovering from HD brain pathology and cognitive deficits.

Transplantation of mesenchymal stem cells overexpressing interleukin-10 induces autophagy response and promotes neuroprotection in a rat model of TBI.

Autophagy, including mitophagy, is critical for neuroprotection in traumatic brain injury (TBI). Transplantation of mesenchymal stem cells (MSCs) provides neuroprotection and induces autophagy by increasing anti-inflammatory cytokines, such as interleukin-10 (IL-10). To evaluate these effects of IL10 that are released by MSCs, we genetically engineered MSCs to overexpress IL10 and compared their effects to unaltered MSCs following transplantation near the site of induced TBIs in rats. Adult, male Sprague-Dawley rats were divided into four groups: Sham + vehicle, TBI + vehicle, TBI + MSCs-IL-10 and TBI + MSCs-GFP. Thirty-six hours post-TBI, the first two groups received vehicle (Hanks balance salt solution), whereas last two groups were transplanted with MSCs-IL-10 or MSCs-GFP. Three weeks after transplantation, biomarkers for neurodegenerative changes, autophagy, mitophagy, cell death and survival markers were measured. We observed a significant increase in the number of dead cells in the cortex and hippocampus in TBI rats, whereas transplantation of MSCs-IL-10 significantly reduced their numbers in comparison to MSCs alone. MSCs-IL-10 rats had increased autophagy, mitophagy and cell survival markers, along with decreased markers for cell death and neuroinflammation. These results suggest that transplantation of MSCs-IL-10 may be an effective strategy to protect against TBI-induced neuronal damage.

Curcumin and Solid Lipid Curcumin Particles Induce Autophagy, but Inhibit Mitophagy and the PI3K-Akt/mTOR Pathway in Cultured Glioblastoma Cells.

Autophagy and the (PI3K-Akt/mTOR) signaling pathway play significant roles in glioblastoma multiforme (GBM) cell death and survival. Curcumin (Cur) has been reported to prevent several cancers, including GBM. However, the poor solubility and limited bioavailability of natural Cur limits its application in preventing GBM growth. Previously, we have shown the greater apoptotic and anti-carcinogenic effects of solid lipid Cur particles (SLCP) than natural Cur in cultured GBM cells. Here, we compared the autophagic responses on cultured U-87MG, GL261, F98, C6-glioma, and N2a cells after treatment with Cur or SLCP (25 µM for 24 h). Different autophagy, mitophagy, and chaperone-mediated autophagy (CMA) markers, along with the PI3K-AKkt/mTOR signaling pathway, and the number of autophagy vacuoles were investigated after treatment with Cur and or SLCP. We observed increased levels of autophagy and decreased levels of mitophagy markers, along with inhibition of the PI3K-Akt/mTOR pathway after treatments with Cur or SLCP. Cell survival markers were downregulated, and cell death markers were upregulated after these treatments. We found greater effects in the case of SCLP-treated cells in comparison to Cur. Given that fewer effects were observed on C-6 glioma and N2a cells. Our results suggest that SLCP could be a safe and effective means of therapeutically modulating autophagy in GBM cells.

A Novel Electromagnetic-Neurobiologic Interface for Functional Animation of Dormant Motor Nerve Roots in Spinal Cord Injury via Neuromodulation.

Complete spinal cord injury is a devastating occurrence afflicting millions of people worldwide with no available treatment for functional motor recovery. In this report, we describe a procedure in which we used parts of a device available for chronic pain treatment to provide a neuromodulation of motor nerve roots in a case with complete motor and sensory paraplegia. By using a retrograde trans-foraminal approach to implant electrodes close to L2-S1 motor nerve roots bilaterally, we were able to stimulate those nerves and induce precise movements at the joints of lower extremity in a T5 complete spinal cord injury case. We believe that our approach shows potential of the device as a rehabilitation system with the possibility of a parallel electric circuitry that can bridge a damaged spinal cord.

Induced Pluripotent Stem Cell-Derived Neural Stem Cell Transplantations Reduced Behavioral Deficits and Ameliorated Neuropathological Changes in YAC128 Mouse Model of Huntington's Disease.

Huntington's disease (HD) is a genetic neurodegenerative disorder characterized by neuronal loss and motor dysfunction. Although there is no effective treatment, stem cell transplantation offers a promising therapeutic strategy, but the safety and efficacy of this approach needs to be optimized. The purpose of this study was to test the potential of intra-striatal transplantation of induced pluripotent stem cell-derived neural stem cells (iPS-NSCs) for treating HD. For this purpose, we developed mouse adenovirus-generated iPSCs, differentiated them into neural stem cells in vitro, labeled them with Hoechst, and transplanted them bilaterally into striata of 10-month old wild type (WT) and HD YAC128 mice. We assessed the efficiency of these transplanted iPS-NSCs to reduce motor deficits in YAC128 mice by testing them on an accelerating rotarod task at 1 day prior to transplantation, and then weekly for 10 weeks. Our results showed an amelioration of locomotor deficits in YAC128 mice that received iPS-NSC transplantations. Following testing, the mice were sacrificed, and their brains were analyzed using immunohistochemistry and Western blot (WB). The results from our histological examinations revealed no signs of tumors and evidence that many iPS-NSCs survived and differentiated into region-specific neurons (medium spiny neurons) in both WT and HD mice, as confirmed by co-labeling of Hoechst-labeled transplanted cells with NeuN and DARPP-32. Also, counts of Hoechst-labeled cells revealed that a higher proportion were co-labeled with DARPP-32 and NeuN in HD-, compared to WT- mice, suggesting a dissimilar differentiation pattern in HD mice. Whereas significant decreases were found in counts of NeuN- and DARPP-32-labeled cells, and for neuronal density measures in striata of HD vehicle controls, such decrements were not observed in the iPS-NSCs-transplanted-HD mice. WB analysis showed increase of BDNF and TrkB levels in striata of transplanted HD mice compared to HD vehicle controls. Collectively, our data suggest that iPS-NSCs may provide an effective option for neuronal replacement therapy in HD.

PAMAM Dendrimers Cross the Blood-Brain Barrier When Administered through the Carotid Artery in C57BL/6J Mice.

Drug delivery into the central nervous system (CNS) is challenging due to the blood-brain barrier (BBB) and drug delivery into the brain overcoming the BBB can be achieved using nanoparticles such as dendrimers. The conventional cationic dendrimers used are highly toxic. Therefore, the present study investigates the role of novel mixed surface dendrimers, which have potentially less toxicity and can cross the BBB when administered through the carotid artery in mice. In vitro experiments investigated the uptake of amine dendrimers (G1-NH2 and G4-NH2) and novel dendrimers (G1-90/10 and G4-90/10) by primary cortical cultures. In vivo experiments involved transplantation of G4-90/10 into mice through (1) invasive intracranial injections into the striatum; and (2) less invasive carotid injections. The animals were sacrificed 24-h and 1-week post-transplantations and their brains were analyzed. In vivo experiments proved that the G4-90/10 can cross the BBB when injected through the carotid artery and localize within neurons and glial cells. The dendrimers were found to migrate through the corpus callosum 1-week post intracranial injection. Immunohistochemistry showed that the migrating cells are the dendrimer-infected glial cells. Overall, our results suggest that poly-amidoamine (PAMAM) dendrimers may be used as a minimally invasive means to deliver biomolecules for treating neurological diseases or disorders.

Solid Lipid Curcumin Particles Induce More DNA Fragmentation and Cell Death in Cultured Human Glioblastoma Cells than Does Natural Curcumin.

Despite recent advancements in cancer therapies, glioblastoma multiforme (GBM) remains largely incurable. Curcumin (Cur), a natural polyphenol, has potent anticancer effects against several malignancies, including metastatic brain tumors. However, its limited bioavailability reduces its efficiency for treating GBM. Recently, we have shown that solid lipid Cur particles (SLCPs) have greater bioavailability and brain tissue penetration. The present study compares the efficiency of cell death by Cur and/or SLCPs in cultured GBM cells derived from human (U-87MG) and mouse (GL261) tissues. Several cell viability and cell death assays and marker proteins (MTT assay, annexin-V staining, TUNEL staining, comet assay, DNA gel electrophoresis, and Western blot) were investigated following the treatment of Cur and/or SLCP (25 µM) for 24-72 h. Relative to Cur, the use of SLCP increased cell death and DNA fragmentation, produced longer DNA tails, and induced more fragmented nuclear lobes. In addition, cultured GBM cells had increased levels of caspase-3, Bax, and p53, with decreases in Bcl2, c-Myc, and both total Akt, as well as phosphorylated Akt, when SLCP, rather Cur, was used. Our in vitro work suggests that the use of SLCP may be a promising strategy for reversing or preventing GBM growth, as compared to using Cur.