The interaction of tPA with NMDAR1 drives neuroinflammation and neurodegeneration in α-synuclein-mediated neurotoxicity.

The thrombolytic protease tissue plasminogen activator (tPA) is expressed in the CNS, where it regulates diverse functions including neuronal plasticity, neuroinflammation, and blood-brain-barrier integrity. However, its role in different brain regions such as the substantia nigra (SN) is largely unexplored. In this study, we characterize tPA expression, activity, and localization in the SN using a combination of retrograde tracing and β-galactosidase tPA reporter mice.

Cerebrospinal fluid dynamics and subarachnoid space occlusion following traumatic spinal cord injury in the pig: an investigation using magnetic resonance imaging.

Background: Traumatic spinal cord injury (SCI) causes spinal cord swelling and occlusion of the subarachnoid space (SAS). SAS occlusion can change pulsatile cerebrospinal fluid (CSF) dynamics, which could have acute clinical management implications. This study aimed to characterise SAS occlusion and investigate CSF dynamics over 14 days post-SCI in the pig.

Identifying depression subtypes and investigating their consistency and transitions in a 1-year cohort analysis.

Major depressive disorder (MDD) is defined by an array of symptoms that make it challenging to understand the condition at a population level. Subtyping offers a way to unpick this phenotypic diversity for improved disorder characterisation. We aimed to identify depression subtypes longitudinally using the Inventory of Depressive Symptomatology: Self-Report (IDS-SR).

The CD74 inhibitor DRhQ improves short-term memory and mitochondrial function in 5xFAD mouse model of Aβ accumulation.

Neuroinflammation and mitochondrial dysfunction are early events in Alzheimer's disease (AD) and contribute to neurodegeneration and cognitive impairment. Evidence suggests that the inflammatory axis mediated by macrophage migration inhibitory factor (MIF) binding to its receptor, CD74, plays an important role in many central nervous system (CNS) disorders such as AD. Our group has developed DRhQ, a novel CD74 binding construct which competitively inhibits MIF binding, blocks macrophage activation and migration into the CNS, enhances anti-inflammatory microglia cell numbers and reduces pro-inflammatory gene expression.

The Value of Multidisciplinary Neuro-oncological Tumor Boards to Increase the Accuracy of FET PET for Identifying Brain Tumor Relapse.

Purpose: Especially in Europe, amino acid PET is increasingly integrated into multidisciplinary neuro-oncological tumor boards (MNTBs) to overcome diagnostic uncertainties such as treatment-related changes. We evaluated the accuracy of MNTB decisions that included the O-(2-[18F]-fluoroethyl)-L-tyrosine (FET) PET information compared with FET PET results alone to differentiate tumor relapse from treatment-related changes.

Patients And Methods: In a single academic center, we retrospectively evaluated 180 MNTB decisions of 151 patients with CNS WHO grade 3 or 4 gliomas (n = 122) or brain metastases (n = 29) presenting equivocal MRI findings following anticancer treatment.

A nomogram for postoperative pain relief in patients with osteoporotic vertebral compression fracture treated with polymethylmethacrylate bone cement.

Osteoporotic vertebral compression fractures (OVCFs) can be painful. Percutaneous kyphoplasty (PKP) aims at strengthening the vertebra and reducing pain, but efficacy can vary among patients. The purpose of this study was to establish a risk prediction model for pain relief following PKP in patients with OVCF.

Trastuzumab deruxtecan in human epidermal growth factor receptor 2-positive breast cancer brain metastases: A systematic review and updated meta-analysis.

Background: Trastuzumab deruxtecan (T-DXd) has shown promising activity in patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer (BC) and central nervous system (CNS) involvement. In this updated meta-analysis, we explore the effectiveness of T-DXd in a large subset of patients with HER2-positive BC and CNS disease.

Methods: A systematic search was made on September 16th, 2024, for studies investigating T-DXd in the scenario of HER2-positive BC and brain metastases (BMs) and/or leptomeningeal disease (LMD).

[ C]Carfentanil PET Whole-Body Imaging of Mu-Opioid Receptors: A First In-Human Study.

Introduction: Mu-opioid receptors (MORs) are G-coupled protein receptors with a high affinity for both endogenous and exogenous opioids. MORs are widely expressed in the central nervous system (CNS), peripheral organs, and the immune system. They mediate pain and reward and have been implicated in the pathophysiology of opioid, cocaine, and other substance use disorders.

Clemastine fumarate accelerates accumulation of disability in progressive multiple sclerosis by enhancing pyroptosis.

Multiple sclerosis (MS) is an immune-mediated demyelinating disease of the central nervous system (CNS). Clemastine fumarate, the over-the-counter antihistamine and muscarinic receptor blocker, has remyelinating potential in MS. A clemastine arm was added to an ongoing platform clinical trial TRAP-MS (NCT03109288) to identify a cerebrospinal fluid (CSF) remyelination signature and to collect safety data on clemastine in patients progressing independently of relapse activity (PIRA).

Diagnosis of primary meningeal natural killer/T‑cell lymphoma of the central nervous system using cerebrospinal fluid cytology: A case report.

Primary central nervous system (CNS) lymphoma of the meninges is a rare tumor that originates in the meninges and does not show parenchymal or systemic spread. CNS involvement by natural killer (NK)/T-cell lymphoma accounts for only 2% of all extranodal NK/T-cell lymphomas, and primary NK/T-cell lymphoma of the meninges is even rarer. The present study reports a case of a 55-year-old male patient with primary NK/T-cell lymphoma.

C3/C3aR Bridges Spinal Astrocyte-Microglia Crosstalk and Accelerates Neuroinflammation in Morphine-Tolerant Rats.

Aims: Communication within glial cells acts as a pivotal intermediary factor in modulating neuroimmune pathology. Meanwhile, an increasing awareness has emerged regarding the detrimental role of glial cells and neuroinflammation in morphine tolerance (MT). This study investigated the influence of crosstalk between astrocyte and microglia on the evolution of morphine tolerance.

Kenny-Caffey Syndrome Type 2 (KCS2): A New Case Report and Patient Follow-Up Optimization.

Kenny-Caffey syndrome 2 (KCS2) is a rare cause of hypoparathyroidism, inherited in an autosomal dominant mode, resulting from pathogenic variants of the gene, which is implicated in intracellular pathways regulating parathormone (PTH) synthesis and skeletal and parathyroid gland development. : The case of a boy is reported, presenting with the characteristic and newly identified clinical, biochemical, radiological, and genetic abnormalities of KCS2. : The proband had noticeable dysmorphic features, and the closure of the anterior fontanel was delayed until the age of 4 years.

Cell state-dependent allelic effects and contextual Mendelian randomization analysis for human brain phenotypes.

Gene expression quantitative trait loci are widely used to infer relationships between genes and central nervous system (CNS) phenotypes; however, the effect of brain disease on these inferences is unclear. Using 2,348,438 single-nuclei profiles from 391 disease-case and control brains, we report 13,939 genes whose expression correlated with genetic variation, of which 16.7-40.

Clavulanic acid prevents paclitaxel-induced neuropathic pain through a systemic and central anti-inflammatory effect in mice.

Paclitaxel (PCX) based treatments, commonly used to treat breast, ovarian and lung cancers, have the highest incidence of chemotherapy-induced neuropathic pain, affecting from 38 to 94 ​% of patients. Unfortunately, analgesic treatments are not always effective for PCX-induced neuropathic pain (PINP). This study aimed to evaluate the antinociceptive effect of clavulanic acid (CLAV), a clinically used β-lactam molecule, in both therapeutic and preventive contexts in mice with PINP.

Current situation of central nervous system tumour survivors in a spanish hospital.

Introduction: Despite the increasing number of central nervous system (CNS) tumour survivors, long-term (LT) sequelae remain a substantial burden on their health through various life stages. The aim of our study was to evaluate late morbidity, health-related quality of life (HRQoL), self-esteem, functional status, adaptive behaviour, physical activity and social outcomes such as education, employment, relationship status and possession of a driver's license, in addition to the role of LT effects of radiotherapy (RTx) on these outcomes.

Methods: The study included 111 CNS tumour survivors with a minimum of 10 years of follow-up.

Carbon-based nanozymes for cancer therapy and diagnosis: A review.

Carbon-based nanozymes (CNs) have emerged as a significant innovation in targeted cancer therapy, demonstrating great potential for advancing cancer diagnosis and treatment. With exceptional catalytic properties, remarkable biocompatibility, and the ability to precisely target cancer cells, CNs provide a promising avenue for the development of novel oncological therapies. By functionalizing their surfaces with targeting ligands, such as antibodies or peptides, CNs can specifically recognize and bind to cancer cells.

Brain distribution study of [C]-Riluzole following intranasal administration in mice.

Amyotrophic lateral sclerosis (ALS) presents a substantial challenge due to its complex nature, limited effective treatment options, and modest benefits from current therapies in slowing disease progression. This study explores the potential of intranasal (IN) delivery to enhance the CNS delivery of riluzole (RLZ), a standard ALS treatment which is subject to blood-brain barrier efflux mechanisms. Additionally, the impact of elacridar (ELC), an efflux pump inhibitor, on IN RLZ CNS bioavailability was examined.

Neuropathology, pathomechanism, and transmission in zoonotic Borna disease virus 1 infection: a systematic review.

Borna disease, which is a severe encephalitis that primarily affects horses and sheep, has been recognised for over two centuries. Borna disease virus 1 (BoDV-1) has been identified as a cause of a predominantly fatal encephalitis in humans. Little scientific data exist regarding the virus' transmission, entry portal, and excretion routes.

Patterns of belatacept use and risk of post-transplant lymphoproliferative disorder in US kidney transplant recipients: An analysis of the Organ Procurement and Transplantation Network database.

Background: Belatacept is approved for the prophylaxis of organ rejection in Epstein-Barr virus (EBV)-seropositive kidney transplant recipients and is associated with a risk of post-transplant lymphoproliferative disorder (PTLD).

Methods: Data from the Organ Procurement and Transplantation Network were used to examine patterns of belatacept use, describe patient characteristics, and estimate risk of PTLD in EBV-seropositive, kidney-only transplant recipients receiving belatacept- or calcineurin inhibitor (CNI)-based immunosuppression as part of US Food and Drug Administration-mandated safety monitoring.

Results: During the study period (June 15, 2011-June 14, 2016), 94.

Repurposing Licensed Drugs with Activity Against Epstein-Barr Virus for Treatment of Multiple Sclerosis: A Systematic Approach.

Background: Epstein-Barr virus (EBV) is implicated as a necessary factor in the development of multiple sclerosis (MS) and may also be a driver of disease activity. Although it is not clear whether ongoing viral replication is the driver for MS pathology, MS researchers have considered the prospect of using drugs with potential efficacy against EBV in the treatment of MS. We have undertaken scientific and lived experience expert panel reviews to shortlist existing licensed therapies that could be used in later-stage clinical trials in MS.

Frontal lobe intra-axial schwannoma harboring a CHD7::VGLL3 fusion and heterozygous TSC2 p.F1510del mutation in a young child.

Background: Brain intraparenchymal schwannoma is a rare clinical entity, generally curable with adequate resection.

Methods And Results: We describe a case in a male patient first presenting at 19 months of age, the youngest reported age for this lesion. It also appears to be the first case connected to a germline TSC2 p.

Temporal Trends of Subsequent CNS Malignancies Among Survivors of Childhood Cancer.

Purpose: It is not known whether temporal changes in childhood cancer therapy have reduced risk of subsequent malignant neoplasms (SMNs) of the central nervous system (CNS), a frequently fatal late effect of cancer therapy.

Methods: Five-year survivors of primary childhood cancers diagnosed between 1970-1999 in the Childhood Cancer Survivor Study with a subsequent CNS SMN were identified. Cumulative incidence rates and standardized incidence ratios (SIR) were compared among survivors diagnosed between 1970-1979 (N = 6223), 1980-1989 (N = 9680), and 1990-1999 (N = 8999).

Anti-neuroinflammatory and Neuroprotective Effects of T-006 on Alzheimer's Disease Models by Modulating TLR4-Mediated MyD88/ NF-κB Signaling.

Introduction: Neuroinflammation derived from the activation of the microglia is considered a vital pathogenic factor of Alzheimer's Disease (AD). T-006, a tetramethylpyrazine derivative, has been found to alleviate cognitive deficits via inhibiting tau expression and phosphorylation in AD transgenic mouse models. Recently, T-006 has been proven to dramatically decrease the levels of total Amyloid β (Aβ) peptide and Glial Fibrillary Acidic Protein (GFAP) and suppress the expression of ionized calcium binding adaptor molecule-1 (Iba-1) in APP/PS1 mice.