Aquaporins: Gatekeepers of Fluid Dynamics in Traumatic Brain Injury.

Aquaporins (AQPs), particularly AQP4, play a crucial role in regulating fluid dynamics in the brain, impacting the development and resolution of edema following traumatic brain injury (TBI). This review examines the alterations in AQP expression and localization post-injury, exploring their effects on brain edema and overall injury outcomes. We discuss the underlying molecular mechanisms regulating AQP expression, highlighting potential therapeutic strategies to modulate AQP function. These insights provide a comprehensive understanding of AQPs in TBI and suggest novel approaches for improving clinical outcomes through targeted interventions.

Diagnostic and Therapeutic Insights into Spinal Glomangioma of a Unique Intradural, Extramedullary Presentation-Systematic Review.

Contemporary literature lacks examples of intradural, extramedullary spinal glomangiomas. Moreover, glomus tumors in general are exceedingly rare among benign spinal tumors and are mostly located within epidural space or within intervertebral foramen, and only a few cases have been documented to date. This report provides a detailed analysis of the clinical presentation, imaging characteristics, surgical intervention, and pathological findings of a 45-year-old patient experiencing progressive locomotor deterioration. The tumor was surgically excised, and subsequent histological examination identified it as a representative of glomus tumors-a glomangioma. Notably, this represents a unique case as it was the first example of such a tumor being discovered intradurally. Radical surgical excision remains the modality of choice in most benign spinal tumors of this localization. Although the malignant transformation of glomus tumors within the spine has not been documented thus far, cases have arisen in other areas. Consequently, we will investigate potential oncological treatments for cases with malignant potential and highlight advancements in surgical techniques for benign intradural spinal tumors.

Aquaporin 2 in Cerebral Edema: Potential Prognostic Marker in Craniocerebral Injuries.

Despite continuous medical advancements, traumatic brain injury (TBI) remains a leading cause of death and disability worldwide. Consequently, there is a pursuit for biomarkers that allow non-invasive monitoring of patients after cranial trauma, potentially improving clinical management and reducing complications and mortality. Aquaporins (AQPs), which are crucial for transmembrane water transport, may be significant in this context. This study included 48 patients, with 27 having acute (aSDH) and 21 having chronic subdural hematoma (cSDH). Blood plasma samples were collected from the participants at three intervals: the first sample before surgery, the second at 15 h, and the third at 30 h post-surgery. Plasma concentrations of AQP1, AQP2, AQP4, and AQP9 were determined using the sandwich ELISA technique. CT scans were performed on all patients pre- and post-surgery. Correlations between variables were examined using Spearman's nonparametric rank correlation coefficient. A strong correlation was found between aquaporin 2 levels and the volume of chronic subdural hematoma and midline shift. However, no significant link was found between aquaporin levels (AQP1, AQP2, AQP4, and AQP9) before and after surgery for acute subdural hematoma, nor for AQP1, AQP4, and AQP9 after surgery for chronic subdural hematoma. In the chronic SDH group, AQP2 plasma concentration negatively correlated with the midline shift measured before surgery (Spearman's ρ -0.54; p = 0.017) and positively with hematoma volume change between baseline and 30 h post-surgery (Spearman's ρ 0.627; p = 0.007). No statistically significant correlation was found between aquaporin plasma levels and hematoma volume for AQP1, AQP2, AQP4, and AQP9 in patients with acute SDH. There is a correlation between chronic subdural hematoma volume, measured radiologically, and serum AQP2 concentration, highlighting aquaporins' potential as clinical biomarkers.

Astroglial Cells: Emerging Therapeutic Targets in the Management of Traumatic Brain Injury.

Traumatic Brain Injury (TBI) represents a significant health concern, necessitating advanced therapeutic interventions. This detailed review explores the critical roles of astrocytes, key cellular constituents of the central nervous system (CNS), in both the pathophysiology and possible rehabilitation of TBI. Following injury, astrocytes exhibit reactive transformations, differentiating into pro-inflammatory (A1) and neuroprotective (A2) phenotypes. This paper elucidates the interactions of astrocytes with neurons, their role in neuroinflammation, and the potential for their therapeutic exploitation. Emphasized strategies encompass the utilization of endocannabinoid and calcium signaling pathways, hormone-based treatments like 17ß-estradiol, biological therapies employing anti-HBGB1 monoclonal antibodies, gene therapy targeting Connexin 43, and the innovative technique of astrocyte transplantation as a means to repair damaged neural tissues.

Diagnosis and Management of Neuropathic Pain in Spine Diseases.

Neuropathic pain is generally defined as a non-physiological pain experience caused by damage to the nervous system. It can occur spontaneously, as a reaction to a given stimulus, or independently of its action, leading to unusual pain sensations usually referred to as firing, burning or throbbing. In the course of spine disorders, pain symptoms commonly occur. According to available epidemiological studies, a neuropathic component of pain is often present in patients with spinal diseases, with a frequency ranging from 36% to 55% of patients. Distinguishing between chronic nociceptive pain and neuropathic pain very often remains a challenge. Consequently, neuropathic pain is often underdiagnosed in patients with spinal diseases. In reference to current guidelines for the treatment of neuropathic pain, gabapentin, serotonin and norepinephrine reuptake inhibitors and tricyclic antidepressants constitute first-line therapeutic agents. However, long-term pharmacologic treatment often leads to developing tolerance and resistance to used medications. Therefore, in recent years, a plethora of therapeutic methods for neuropathic pain have been developed and investigated to improve clinical outcomes. In this review, we briefly summarized current knowledge about the pathophysiology and diagnosis of neuropathic pain. Moreover, we described the most effective treatment approaches for neuropathic pain and discussed their relevance in the treatment of spinal pain.

Biological and Clinical Aspects of Metastatic Spinal Tumors.

Spine metastases are a common life-threatening complication of advanced-stage malignancies and often result in poor prognosis. Symptomatic spine metastases develop in the course of about 10% of malignant neoplasms. Therefore, it is essential for contemporary medicine to understand metastatic processes in order to find appropriate, targeted therapeutic options. Thanks to continuous research, there appears more and more detailed knowledge about cancer and metastasis, but these transformations are extremely complicated, e.g., due to the complexity of reactions, the variety of places where they occur, or the participation of both tumor cells and host cells in these transitions. The right target points in tumor metastasis mechanisms are still being researched; that will help us in the proper diagnosis as well as in finding the right treatment. In this literature review, we described the current knowledge about the molecular pathways and biomarkers engaged in metastatic processes involving the spine. We also presented a current bone-targeted treatment for spine metastases and the emerging therapies targeting the discussed molecular mechanisms.

Low-Cost Cranioplasty-A Systematic Review of 3D Printing in Medicine.

The high cost of biofabricated titanium mesh plates can make them out of reach for hospitals in low-income countries. To increase the availability of cranioplasty, the authors of this work investigated the production of polymer-based endoprostheses. Recently, cheap, popular desktop 3D printers have generated sufficient opportunities to provide patients with on-demand and on-site help. This study also examines the technologies of 3D printing, including SLM, SLS, FFF, DLP, and SLA. The authors focused their interest on the materials in fabrication, which include PLA, ABS, PET-G, PEEK, and PMMA. Three-dimensional printed prostheses are modeled using widely available CAD software with the help of patient-specific DICOM files. Even though the topic is insufficiently researched, it can be perceived as a relatively safe procedure with a minimal complication rate. There have also been some initial studies on the costs and legal regulations. Early case studies provide information on dozens of patients living with self-made prostheses and who are experiencing significant improvements in their quality of life. Budget 3D-printed endoprostheses are reliable and are reported to be significantly cheaper than the popular counterparts manufactured from polypropylene polyester.

Metallic Implants Used in Lumbar Interbody Fusion.

Over the last decade, pedicle fixation systems have evolved and modifications in spinal fusion techniques have been developed to increase fusion rates and improve clinical outcomes after lumbar interbody fusion (LIF). Regarding materials used for screw and rod manufacturing, metals, especially titanium alloys, are the most popular resources. In the case of pedicle screws, that biomaterial can be also doped with hydroxyapatite, CaP, ECM, or tantalum. Other materials used for rod fabrication include cobalt-chromium alloys and nitinol (nickel-titanium alloy). In terms of mechanical properties, the ideal implant used in LIF should have high tensile and fatigue strength, Young's modulus similar to that of the bone, and should be 100% resistant to corrosion to avoid mechanical failures. On the other hand, a comprehensive understanding of cellular and molecular pathways is essential to identify preferable characteristics of implanted biomaterial to obtain fusion and avoid implant loosening. Implanted material elicits a biological response driven by immune cells at the site of insertion. These reactions are subdivided into innate (primary cellular response with no previous exposure) and adaptive (a specific type of reaction induced after earlier exposure to the antigen) and are responsible for wound healing, fusion, and also adverse reactions, i.e., hypersensitivity. The main purposes of this literature review are to summarize the physical and mechanical properties of metal alloys used for spinal instrumentation in LIF which include fatigue strength, Young's modulus, and corrosion resistance. Moreover, we also focused on describing biological response after their implantation into the human body. Our review paper is mainly focused on titanium, cobalt-chromium, nickel-titanium (nitinol), and stainless steel alloys.

Hydroxyapatite Use in Spine Surgery-Molecular and Clinical Aspect.

Hydroxyapatite possesses desirable properties as a scaffold in tissue engineering: it is biocompatible at a site of implantation, and it is degradable to non-toxic products. Moreover, its porosity enables infiltration of cells, nutrients and waste products. The outcome of hydroxyapatite implantation highly depends on the extent of the host immune response. Authors emphasise major roles of the chemical, morphological and physical properties of the surface of biomaterial used. A number of techniques have been applied to transform the theoretical osteoconductive features of HAp into spinal fusion systems-from integration of HAp with autograft to synthetic intervertebral implants. The most popular uses of HAp in spine surgery include implants (ACDF), bone grafts in posterolateral lumbar fusion and transpedicular screws coating. In the past, autologous bone graft has been used as an intervertebral cage in ACDF. Due to the morbidity related to autograft harvesting from the iliac bone, a synthetic cage with osteoconductive material such as hydroxyapatite seems to be a good alternative. Regarding posterolateral lumbar fusion, it requires the graft to induce new bone growth and reinforce fusion between the vertebrae. Hydroxyapatite formulations have shown good results in that field. Moreover, the HAp coating has proven to be an efficient method of increasing screw fixation strength. It can decrease the risk of complications such as screw loosening after pedicle screw fixation in osteoporotic patients. The purpose of this literature review is to describe in vivo reaction to HAp implants and to summarise its current application in spine surgery.

PD-L1/miR-155 Interplay in Pediatric High-Grade Glioma.

High-grade pediatric glioma (p-HGG-WHO 2021, formerly GBM-WHO 2016), as a common, aggressive, and highly lethal primary brain malignancy in adults, accounts for only 3-15% of primary brain tumors in pediatric patients. After leukemia, brain malignancies are the second most common in the pediatric population and first in incidences concerning solid tumors. This study was designed on the basis of 14 pediatric patients hospitalized at Children's Memorial Health Institute in Warsaw, Poland, due to p-HGG treatment. All the patients had a histopathological diagnosis performed by an experienced neuropathologist according to WHO guidelines (WHO 2016 Grade IV Glioblastoma). A significant correlation was found between the miR-155 concentration and the level of PD-L1 expression in p-HGG tumor tissue. Very few reports have indicated PD-L1 expression in pediatric patients.

New Horizons for Hydroxyapatite Supported by DXA Assessment-A Preliminary Study.

Dual Energy X-ray Absorptiometry (DXA) is a tool that allows the assessment of bone density. It was first presented by Cameron and Sorenson in 1963 and was approved by the Food and Drug Administration. Misplacing the femoral neck box, placing a trochanteric line below the midland and improper placement of boundary lines are the most common errors made during a DXA diagnostic test made by auto analysis. Hydroxyapatite is the most important inorganic component of teeth and bone tissue. It is estimated to constitute up to 70% of human bone weight and up to 50% of its volume. Calcium phosphate comes in many forms; however, studies have shown that only tricalcium phosphate and hydroxyapatite have the characteristics that allow their use as bone-substituted materials. The purpose of this study is aimed at analyzing the results of hip densitometry and hydorxyapatite distribution in order to better assess the structure and mineral density of the femoral neck. However, a detailed analysis of the individual density curves shows some qualitative differences that may be important in assessing bone strength in the area under study. To draw more specific conclusions on the therapy applied for individual patients, we need to determine the correct orientation of the bone from the resulting density and document the trends in the density distribution change. The average results presented with the DXA method are insufficient.

Molecular Mechanisms and Clinical Application of Multipotent Stem Cells for Spinal Cord Injury.

Spinal Cord Injury (SCI) is a common neurological disorder with devastating psychical and psychosocial sequelae. The majority of patients after SCI suffer from permanent disability caused by motor dysfunction, impaired sensation, neuropathic pain, spasticity as well as urinary complications, and a small number of patients experience a complete recovery. Current standard treatment modalities of the SCI aim to prevent secondary injury and provide limited recovery of lost neurological functions. Stem Cell Therapy (SCT) represents an emerging treatment approach using the differentiation, paracrine, and self-renewal capabilities of stem cells to regenerate the injured spinal cord. To date, multipotent stem cells including mesenchymal stem cells (MSCs), neural stem cells (NSCs), and hematopoietic stem cells (HSCs) represent the most investigated types of stem cells for the treatment of SCI in preclinical and clinical studies. The microenvironment of SCI has a significant impact on the survival, proliferation, and differentiation of transplanted stem cells. Therefore, a deep understanding of the pathophysiology of SCI and molecular mechanisms through which stem cells act may help improve the treatment efficacy of SCT and find new therapeutic approaches such as stem-cell-derived exosomes, gene-modified stem cells, scaffolds, and nanomaterials. In this literature review, the pathogenesis of SCI and molecular mechanisms of action of multipotent stem cells including MSCs, NSCs, and HSCs are comprehensively described. Moreover, the clinical efficacy of multipotent stem cells in SCI treatment, an optimal protocol of stem cell administration, and recent therapeutic approaches based on or combined with SCT are also discussed.

PD-L1 Expression Correlated with p53 Expression in Pediatric Glioblastoma Multiforme.

High-grade gliomas are infrequent in the pediatric population compared to adults, nevertheless, mortality and morbidity caused by malignant gliomas in this group of patients remain significant. PD-L1 and PD-1 Immune checkpoints (IC) molecules maintain immunological balance between activation and suppression. Eighteen patients with a histopathological diagnosis of pediatric glioblastoma multiforme (GBM, WHO IV) were studied. In total, PD-L1 expression was detected in 8 patients (44%). The molecular aspect of IC and immunotherapy targeted on PD-1/PD-L1 axis in pediatric population may be a promising adjuvant therapy in pediatric glioblastoma multiform treatment, however, this subject requires further investigation.

IFN-γ Correlations with Pain Assessment, Radiological Findings, and Clinical Intercourse in Patient after Lumbar Microdiscectomy: Preliminary Study.

OBJECTIVES: We investigated the influence of pain decrease after lumbar microdiscectomy on the interferon gamma (IFN-γ) serum level in patients with lumbar disc herniations. The study challenges the mechanism of sciatica pain and the role of IFN-γ in radicular pain development. Material and Methods. We performed clinical and immunoenzymatic assessment in a group of 27 patients with lumbar radicular pain due to disc herniations before and 3 months after surgery. Clinical status was assessed with the use of the Numeric Rating Scale (NRS), the Pain Rating Index and Pain Intensity Index of McGill Pain Questionnaire (SF-MPQ), the Oswestry Disability Index (ODI), and Beck Depression Inventory (BDI). The plasma concentrations of IFN-γ were ascertained by an immunoenzymatic method. RESULTS: We observe significant correlations between the results of the pain in the back region assessment NRS back scale after the surgery with the level of IFN-γ before the procedure (r s = 0.528; p = 0.008) and after the procedure (r s = 0.455; p = 0.025). These are moderate and positive correlations-the decrease in pain is correlated with the lower IFN-γ level. Additionally, there are significant correlations between the results of the PRI scale and the IFN-γ level. The PRI score before surgery correlates positively with IFN-γ after surgery (r s = 0.462; p = 0.023), and the PRI score after surgery correlates positively with IFN before surgery (r s = 0.529; p = 0.005) and after surgery (r s = 0.549; p = 0.003). All correlations are moderate in severity-severe pain before surgery correlates with a higher level of IFN-γ after surgery and also higher IFN-γ before surgery. There were significant differences in the IFN-γ level before (Z = -2.733; p = 0.006) and after (Z = -2.391; p = 0.017) surgery in the groups of patients with and without nerve compression. In the group of patients with nerve compression, the level of IFN-γ before and after surgery was lower. CONCLUSIONS: Less pain ratio after operation correlates with the level of IFN-γ. In the group of patients without significant nerve compression confirmed by MRI scans, the level of IFN-γ before and after surgery was higher than that in the group with nerve root compression.

Recent Trends of microRNA Significance in Pediatric Population Glioblastoma and Current Knowledge of Micro RNA Function in Glioblastoma Multiforme.

Central nervous system tumors are a significant problem for modern medicine because of their location. The explanation of the importance of microRNA (miRNA) in the development of cancerous changes plays an important role in this respect. The first papers describing the presence of miRNA were published in the 1990s. The role of miRNA has been pointed out in many medical conditions such as kidney disease, diabetes, neurodegenerative disorder, arthritis and cancer. There are several miRNAs responsible for invasiveness, apoptosis, resistance to treatment, angiogenesis, proliferation and immunology, and many others. The research conducted in recent years analyzing this group of tumors has shown the important role of miRNA in the course of gliomagenesis. These particles seem to participate in many stages of the development of cancer processes, such as proliferation, angiogenesis, regulation of apoptosis or cell resistance to cytostatics.

TLR-4 Signaling vs. Immune Checkpoints, miRNAs Molecules, Cancer Stem Cells, and Wingless-Signaling Interplay in Glioblastoma Multiforme-Future Perspectives.

Toll-like-receptor (TLR) family members were detected in the central nervous system (CNS). TLR occurrence was noticed and widely described in glioblastomamultiforme (GBM) cells. After ligand attachment, TLR-4 reorients domains and dimerizes, activates an intracellular cascade, and promotes further cytoplasmatic signaling. There is evidence pointing at a strong relation between TLR-4 signaling and micro ribonucleic acid (miRNA) expression. The TLR-4/miRNA interplay changes typical signaling and encourages them to be a target for modern immunotherapy. TLR-4 agonists initiate signaling and promote programmed death ligand-1 (PD-1L) expression. Most of those molecules are intensively expressed in the GBM microenvironment, resulting in the autocrine induction of regional immunosuppression. Another potential target for immunotreatment is connected with limited TLR-4 signaling that promotes Wnt/DKK-3/claudine-5 signaling, resulting in a limitation of GBM invasiveness. Interestingly, TLR-4 expression results in bordering proliferative trends in cancer stem cells (CSC) and GBM. All of these potential targets could bring new hope for patients suffering from this incurable disease. Clinical trials concerning TLR-4 signaling inhibition/promotion in many cancers are recruiting patients. There is still a lot to do in the field of GBM immunotherapy.

Initial Factors Affecting 6-month Outcome of Patients Undergoing Surgery for Acute Post-traumatic Subdural and Epidural Hematoma.

INTRODUCTION: The most frequent consequences of a traumatic brain injury are acute subdural (SDH) and epidural hematoma (EDH), which usually require a surgical treatment. Most of the factors affecting the prognosis have been analyzed on a wide group of traumatic brain injuries. Nonetheless, there are few studies analyzing factors influencing the prognosis regarding patients with EDH and SDH. The aim of the study is to identify factors which have prognostic value in relation to 6-month outcome of patients undergoing surgery for acute hematoma. PATIENTS AND METHODS: The study included a group of 128 patients with isolated craniocerebral injuries. The patients were divided into two groups, namely a group of 28 patients operated on due to epidural hematoma and a group of 100 patients operated on due to acute subdural hematoma. All patients were operated and treated in the Department of Neurosurgery at the Medical University in Lublin from 1.10.2014 to 31.08.2017. The following factors from the groups were analyzed: demographic data, physiological factors, laboratory factors, computed tomography scan characteristics, and time between the trauma and the surgery. All the factors were correlated with six-month outcome in Glasgow outcome scale. RESULTS: The univariate analysis has confirmed the influence of many factors affecting the outcomes. CONCLUSION: It is interesting that the factors such as GSC score, saturation, respiratory rate, and systolic blood pressure were associated with outcome with highly statistically significant differences in both group. These are factors that, with an appropriate treatment, could be normalized at the place of the accident.

The Initial Factors with Strong Predictive Value in Relation to Six-Month Outcome among Patients Operated due to Extra-Axial Hematomas.

INTRODUCTION: Traumatic brain injuries (TBI) are a real social problem, with an upward trend worldwide. The most frequent consequence of a traumatic brain injury is extra-axial hemorrhage, i.e., an acute subdural (SDH) and epidural hematoma (EDH). Most of the factors affecting the prognosis have been analyzed on a wide group of traumatic brain injuries. Nonetheless, there are few studies analyzing factors influencing the prognosis regarding patients undergoing surgery due to acute subdural and epidural hematoma. The aim of this study was to identify the factors which have the strongest prognostic value in relation to the 6-month outcome of the patients undergoing surgery for SDH and EDH. PATIENTS AND METHODS: The study included a group of 128 patients with isolated craniocerebral injuries. Twenty eight patients were operated upon due to EDH, and a group of 100 patients were operated upon due to SDH. The following factors from the groups were analyzed: demographic data, physiological factors, laboratory factors, computed tomography scan characteristics, and time between the trauma and the surgery. All of these factors were correlated in a multivariate analysis with the six-month outcome in the Glasgow outcome scale. RESULTS: The factors with the strongest prognostic value are GCS score, respiration rate, saturation, glycaemia and systolic blood pressure. CONCLUSION: Initial GCS score, respiratory rate, saturation, glycaemia and systolic blood pressure were the factors with the strongest prognostic value.

Micro RNA Molecules as Modulators of Treatment Resistance, Immune Checkpoints Controllers and Sensitive Biomarkers in Glioblastoma Multiforme.

Based on genome sequencing, it is estimated that over 90% of genes stored in human genetic material are transcribed, but only 3% of them contain the information needed for the production of body proteins. This group also includes micro RNAs representing about 1%-3% of the human genome. Recent studies confirmed the hypothesis that targeting molecules called Immune Checkpoint (IC) open new opportunities to take control over glioblastoma multiforme (GBM). Detection of markers that indicate the presence of the cancer occupies a very important place in modern oncology. This function can be performed by both the cancer cells themselves as well as their components and other substances detected in the patients' bodies. Efforts have been made for many years to find a suitable marker useful in the diagnosis and monitoring of gliomas, including glioblastoma.

Metformin as Potential Therapy for High-Grade Glioma.

Metformin (MET), 1,1-dimethylbiguanide hydrochloride, is a biguanide drug used as the first-line medication in the treatment of type 2 diabetes. The recent years have brought many observations showing metformin in its new role. The drug, commonly used in the therapy of diabetes, may also find application in the therapy of a vast variety of tumors. Its effectiveness has been demonstrated in colon, breast, prostate, pancreatic cancer, leukemia, melanoma, lung and endometrial carcinoma, as well as in gliomas. This is especially important in light of the poor options offered to patients in the case of high-grade gliomas, which include glioblastoma (GBM). A thorough understanding of the mechanism of action of metformin can make it possible to discover new drugs that could be used in neoplasm therapy.