Ectodomain shedding (ES) is a fundamental process involving the proteolytic cleavage of membrane-bound proteins, leading to the release of soluble extracellular fragments (shed ectodomains) with potential paracrine and autocrine signaling functions. In the central nervous system (CNS), ES plays pivotal roles in brain development, axonal regulation, synapse formation, and disease pathogenesis, spanning from cancer to Alzheimer\'s disease. Recent evidence also suggests its potential involvement in neurodevelopmental conditions like autism and schizophrenia. Past investigations of ES in the CNS have primarily relied on cell culture supernatants or cerebrospinal fluid (CSF) samples, but these methods have limitations, offering limited insights into how ES is modulated in the intact brain parenchyma. In this study, we introduce a methodology for analyzing shed ectodomains globally within rodent brain samples. Through biochemical tissue subcellular separation, mass spectrometry, and bioinformatic analysis, we show that the brain\'s soluble fraction sheddome shares significant molecular and functional similarities with in vitro neuronal and CSF sheddomes. This approach provides a promising means of exploring ES dynamics in the CNS, allowing for the evaluation of ES at different developmental stages and pathophysiological states. This methodology has the potential to help us deepen our understanding of ES and its role in CNS function and pathology, offering new insights and opportunities for research in this field.

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Neuro-Behçet\'s disease (NBD) represents a significant complication of Behçet\'s syndrome, potentially leading to elevated mortality and disability rates. The standard treatment for parenchymal NBD typically entails administering high-dose corticosteroids to prompt rapid-onset effects, coupled with immunosuppressants to prevent subsequent relapses. A 48-year-old male with NBD presented with progressively worsening dysarthria over 9 months. This patient experienced increased intraocular pressure while using glucocorticoids, which worsened his pre-existing glaucoma. The patient had a prior diagnosis of NBD and presented with progressive dysarthria over a period of nine months, leading to a brain magnetic resonance imaging (MRI) scan. The brain MRI revealed multifocal punctate high signal intensities in the left frontoparietal area, insula, and basal ganglia. Instead of the standard steroid pulse therapy, the patient received adalimumab-cyclophosphamide combination as an alternative induction therapy. Subsequent serial brain MRI scans exhibited no emergence of new lesions, and the patient remained devoid of clinical relapses even after 17 months from the commencement of induction treatment. Adalimumab-cyclophosphamide combination could be used as a corticosteroid-free induction strategy for NBD. Further investigations are warranted to establish the most suitable combination regimen.

Receptor protein tyrosine phosphatases γ and ζ (RPTPγ and RPTPζ) are transmembrane signaling proteins with extracellular carbonic anhydrase-like domains that play vital roles in the development and functioning of the central nervous system (CNS) and are implicated in tumor suppression, neurodegeneration, and sensing of extracellular [CO2] and [HCO3 -]. RPTPγ expresses throughout the body, whereas RPTPζ preferentially expresses in the CNS. Here, we investigate differential RPTPγ-RPTPζ expression in three sources derived from a wild-type laboratory strain of C57BL/6 mice: (a) mixed neuron-astrocyte hippocampal (HC) cultures 14 days post isolation from P0-P2 pups; (b) P0-P2 pup hippocampi; and (c) 9- to 12-week-old adult hippocampi. Regarding RPTPγ, we detect the Ptprg variant-1 (V1) transcript, representing canonical exons 1-30. Moreover, we newly validate the hypothetical assembly [XM_006517956] (propose name, Ptprg-V3), which lacks exon 14. Both transcripts are in all three HC sources. Regarding RPTPζ, we confirm the expression of Ptprz1-V1, detecting it in pups and adults but not in cultures, and Ptprz1-V3 through Ptprz1-V7 in all three preparations. We newly validate hypothetical assemblies Ptprz1-X1 (in cultures and pups), Ptprz1-X2 (in all three), and Ptprz1-X5 (in pups and adults) and propose to re-designate them as Ptprz1-V0, Ptprz1-V2, and Ptprz1-V8, respectively. The diversity of RPTPγ and RPTPζ splice variants likely corresponds to distinct signaling functions, in different cellular compartments, during development vs later life. In contrast to previous studies that report divergent RPTPγ and RPTPζ protein expressions in neurons and sometimes in the glia, we observe that RPTPγ and RPTPζ co-express in the somata and processes of almost all HC neurons but not in astrocytes, in all three HC preparations.

A 67-year-old male presented to the emergency department with a 7-day history of fever, malaise, myalgia, headache, and a seizure episode. Physical examination showed stable vital signs but a fever. Laboratory tests indicated leukocytosis, anemia, thrombocytosis, and elevated inflammatory markers. Imaging revealed multiple intracranial lesions, and cerebrospinal fluid analysis confirmed the presence of acid-fast bacilli. The patient responded well to anti-tuberculosis therapy, showing significant clinical improvement within 8 weeks.

The papillary tumor of the pineal region (PTPR) is a rare neuroepithelial tumor originating from specialized ependymocytes. It primarily affects structures within the pineal region, including the pineal gland, epithalamus, quadrigeminal cistern, and posterior wall of the third ventricle. Here, we present a series of four cases characterized by symptoms associated with obstructive hydrocephalus such as headaches, seizures, visual disturbances, gait disturbances, and Parinaud syndrome. Imaging studies revealed lesions in the pineal region, prompting surgical intervention. Histopathological examination, including biopsy and intraoperative analysis, confirmed the diagnosis of PTPR. Despite advancements, the etiology and pathogenesis of PTPR remain incompletely understood, warranting further research to refine management strategies.

Clothianidin (CLO), a neonicotinoid that is widely used in forests and agricultural areas, was recently reported to cause toxicity in mammals. Although sensitivity to chemicals varies between sexes and developmental stages, studies that comprehensively evaluate both males and females are limited. Therefore, in this study we utilized murine models to compare the sex-specific differences in behavioral effects following CLO exposure at different developmental stages. We orally administered CLO to male and female mice as a single high-dose solution (80 mg/kg) during the postnatal period (2-week-old), adolescence (6-week-old), or maturity (10-week-old), and subsequently evaluated higher brain function. The behavioral battery test consisted of open field, light/dark transition, and contextual/cued fear conditioning tests conducted at three and seven months of age. After the behavioral test, the brains were dissected and prepared for immunohistochemical staining. We observed behavioral abnormalities in anxiety, spatial memory, and cued memory only in female mice. Moreover, the immunohistochemical analysis showed a reduction in astrocytes within the hippocampus of female mice with behavioral abnormalities. The behavioral abnormalities observed in female CLO-treated mice were consistent with the typical behavioral abnormalities associated with hippocampal astrocyte dysfunction. It is therefore possible that the CLO-induced behavioral abnormalities are at least in part related to a reduction in astrocyte numbers. The results of this study highlight the differences in behavioral effects following CLO exposure between sexes and developmental stages.

BACKGROUND: Spinal tuberculosis is often associated with poor outcomes; host-directed inflammation involving the spine contributes to this disability.
METHODS: A retrospective review of patients with complicated spinal tuberculosis having received tumor necrosis factor-alpha (TNF-α) antagonists at a referral hospital in South Africa. A literature review was performed to identify all published cases of complicated spinal tuberculosis that received a TNF-α antagonist as part of their treatment.
RESULTS: We describe 23 cases, of which 19 were previously reported in the literature. All patients were treated with either thalidomide (n=6) or infliximab (n=16), except for one who received both. All in all, 21 (91%) cases improved neurologically and, at the end of follow-up, 18 could walk.
CONCLUSIONS: There is accumulating experience to confer the efficacy and safety of TNF-α antagonists in treating complicated spinal tuberculosis cases. Evidence from randomized controlled trials is urgently required to substantiate these findings.

OBJECTIVE: The majority of neuromyelitis optica spectrum disorders (NMOSD) patients are seropositive for aquaporin-4 (AQP4)-specific antibodies [also named neuromyelitis optica immunoglobulin G antibodies (NMO-IgG)]. Although NMO-IgG can induce pathological changes in the central nervous system (CNS), the immunological changes in the CNS and peripheral tissue remain largely unknown. We investigated whether NMO-IgG binds to tissue expressing AQP4 and induces immunological changes in the peripheral tissue and CNS.
METHODS: C57BL/6 female mice were assigned into an NMOSD or control group. Pathological and immunological changes in peripheral tissue and CNS were measured by immunostaining and flow cytometry, respectively. Motor impairment was measured by open-field test.
RESULTS: We found that NMO-IgG did bind to astrocyte- and AQP4-expressing peripheral tissue, but induced glial fibrillary acidic protein and AQP4 loss only in the CNS. NMO-IgG induced the activation of microglia and modulated microglia polarization toward the classical (M1) phenotype, but did not affect innate or adaptive immune cells in the peripheral immune system, such as macrophages, neutrophils, Th17/Th1, or IL-10-producing B cells. In addition, NMOSD mice showed significantly less total distance traveled and higher immobility time in the open field.
CONCLUSIONS: We found that injection of human NMO-IgG led to astrocytopathic lesions with microglial activation in the CNS. However, there were no significant pathological or immunological changes in the peripheral tissues.

OBJECTIVE: Cancers of the central nervous system (CNS) pose a significant burden, despite their relatively low incidence compared to other types of cancers. The mortality-to-incidence ratio (MIR) is a crucial indicator of long-term survival and healthcare system performance. Computed tomography (CT) plays a crucial role in the screening, diagnosis, and monitoring of brain tumors, enabling early intervention and treatment. This study aimed to explore the relationship between CT density, CNS cancer incidence, mortality, and MIR to investigate regional variations in CT utilization and their impact on CNS cancer mortality rates.
METHODS: Changes in MIR, referred to as δMIR, were calculated based on data from 2012 and 2018. CT density data for the year 2013 were retrieved from the Global Health Observatory data repository. The association between variables was analyzed using Spearman\'s rank correlation coefficient.
RESULTS: Analysis of data from 107 countries revealed a positive association between CT density and both CNS cancer incidence and mortality. However, a trend was observed between CT density and MIR. These findings suggest that in countries with greater accessibility to CT imaging, CNS cancer cases may be detected earlier and lower mortality rates can be achieved.
CONCLUSIONS: Our research contributes to the understanding of the impact of CT imaging on the management and outcomes of CNS cancers. It informs healthcare strategies and resource allocation to improve patient care.