Explore the vast range of titles available.

Cerebrospinal fluid (CSF) analysis is a diagnostic tool for many conditions affecting the central nervous system. Urgent indications for lumbar puncture include suspected central nervous system infection or subarachnoid hemorrhage. CSF analysis is not necessarily diagnostic but can be useful in the evaluation of other neurologic conditions, such as spontaneous intracranial hypotension, idiopathic intracranial hypertension, multiple sclerosis, Guillain-Barré syndrome, and malignancy. Bacterial meningitis has a high mortality rate and characteristic effects on CSF white blood cell counts, CSF protein levels, and the CSF:serum glucose ratio. CSF culture can identify causative organisms and antibiotic sensitivities. Viral meningitis can present similarly to bacterial meningitis but usually has a low mortality rate. Adjunctive tests such as CSF lactate measurement, latex agglutination, and polymerase chain reaction testing can help differentiate between bacterial and viral causes of meningitis. Immunocompromised patients may have meningitis caused by tuberculosis, neurosyphilis, or fungal or parasitic infections. Subarachnoid hemorrhage has a high mortality rate, and rapid diagnosis is key to improve outcomes. Computed tomography of the head is nearly 100% sensitive for subarachnoid hemorrhage in the first six hours after symptom onset, but CSF analysis may be required if there is a delay in presentation or if imaging findings are equivocal. Xanthochromia and an elevated red blood cell count are characteristic CSF findings in patients with subarachnoid hemorrhage. Leptomeningeal carcinomatosis can mimic central nervous system infection. It has a poor prognosis, and large-volume CSF cytology is diagnostic.

This informative book aligns young readers with top scientists, doctors, and researchers from around the world in the field of neurobiology.

Tolebrutinib is an oral, CNS-penetrant, irreversible inhibitor of Bruton’s tyrosine kinase, an enzyme expressed in B lymphocytes and myeloid cells including microglia, which are major drivers of inflammation in multiple sclerosis. We aimed to determine the dose-response relationship between tolebrutinib and the reduction in new active brain MRI lesions in patients with relapsing multiple sclerosis. We did a 16-week, phase 2b, randomised, double-blind, placebo-controlled, crossover, dose-finding trial at 40 centres (academic sites, specialty clinics, and general neurology centres) in ten countries in Europe and North America. Eligible participants were adults aged 18–55 years with diagnosed relapsing multiple sclerosis (either relapsing-remitting or relapsing secondary progressive multiple sclerosis), and one or more of the following criteria: at least one relapse within the previous year, at least two relapses within the previous 2 years, or at least one active gadolinium-enhancing brain lesion in the 6 months before screening. Exclusion criteria included a diagnosis of primary progressive multiple sclerosis or a diagnosis of secondary progressive multiple sclerosis without relapse. We used a two-step randomisation process to randomly assign eligible participants (1:1) to two cohorts, then further randomly assign participants in each cohort (1:1:1:1) to four tolebrutinib dose groups (5, 15, 30, and 60 mg administered once daily as an oral tablet). Cohort 1 received tolebrutinib for 12 weeks, then matched placebo (ie, identical looking tablets) for 4 weeks; cohort 2 received 4 weeks of placebo followed by 12 weeks of tolebrutinib. Participants and investigators were masked for dose and tolebrutinib-placebo administration sequence; investigators, study team members, and study participants did not have access to unmasked data. MRI scans were done at screening and every 4 weeks over 16 weeks. The primary efficacy endpoint was the number of new gadolinium-enhancing lesions detected on the scan done after 12 weeks of tolebrutinib treatment (assessed at week 12 for cohort 1 and week 16 for cohort 2), relative to the scan done 4 weeks previously, and compared with the lesions accumulated during 4 weeks of placebo run-in period in cohort 2. Efficacy data were analysed in a modified intention-to-treat population, using a two-step multiple comparison procedure with modelling analysis. Safety was assessed for all participants who received at least one dose of study drug. This trial is registered with ClinicalTrials.gov (NCT03889639), EudraCT (2018-003927-12), and WHO (U1111-1220-0572), and has been completed. Between May 14, 2019, and Jan 2, 2020, we enrolled and randomly assigned 130 participants to tolebrutinib: 33 to 5 mg, 32 to 15 mg, 33 to 30 mg, and 32 to 60 mg. 129 (99%) completed the treatment regimen and 126 were included in the primary analysis. At treatment week 12, there was a dose-dependent reduction in the number of new gadolinium-enhancing lesions (mean [SD] lesions per patient: placebo, 1·03 [2·50]; 5 mg, 1·39 [3·20]; 15 mg, 0·77 [1·48]; 30 mg, 0·76 [3·31]; 60 mg, 0·13 [0·43]; p=0·03). One serious adverse event was reported (one patient in the 60 mg group was admitted to hospital because of a multiple sclerosis relapse). The most common non-serious adverse event during tolebrutinib treatment was headache (in one [3%] of 33 in the 5 mg group; three [9%] of 32 in the 15 mg group; one [3%] of 33 in the 30 mg group; and four [13%] of 32 in the 60 mg group). No safety-related discontinuations or treatment-related deaths occurred. 12 weeks of tolebrutinib treatment led to a dose-dependent reduction in new gadolinium-enhancing lesions, the 60 mg dose being the most efficacious, and the drug was well tolerated. Reduction of acute inflammation, combined with the potential to modulate the immune response within the CNS, provides a scientific rationale to pursue phase 3 clinical trials of tolebrutinib in patients with relapsing and progressive forms of multiple sclerosis. Sanofi.

\"A feminist view of the intimate stranger that is the brain, and an overdue reckoning with the misogyny and racism within neuroscience\"-- Provided by publisher.

Myelin is required for the function of neuronal axons in the central nervous system, but the mechanisms that support myelin health are unclear. Although macrophages in the central nervous system have been implicated in myelin health 1 , it is unknown which macrophage populations are involved and which aspects they influence. Here we show that resident microglia are crucial for the maintenance of myelin health in adulthood in both mice and humans. We demonstrate that microglia are dispensable for developmental myelin ensheathment. However, they are required for subsequent regulation of myelin growth and associated cognitive function, and for preservation of myelin integrity by preventing its degeneration. We show that loss of myelin health due to the absence of microglia is associated with the appearance of a myelinating oligodendrocyte state with altered lipid metabolism. Moreover, this mechanism is regulated through disruption of the TGFβ1–TGFβR1 axis. Our findings highlight microglia as promising therapeutic targets for conditions in which myelin growth and integrity are dysregulated, such as in ageing and neurodegenerative disease 2 , 3 . Resident microglia in the central nervous system are identified as the specific macrophage population that regulates myelin growth and integrity.

Overview: In the past, the brain was considered an autonomous organ, self-contained and completely separate from the body's immune system. But over the past twenty years, neuroimmunologist Michal Schwartz, together with her research team, not only has overturned this misconception but has brought to light revolutionary new understandings of brain health and repair. In this book Schwartz describes her research journey, her experiments, and the triumphs and setbacks that led to the discovery of connections between immune system and brain. Michal Schwartz, with Anat London, also explains the significance of the findings for future treatments of brain disorders and injuries, spinal cord injuries, glaucoma, depression, and other conditions such as brain aging and Alzheimer's and Parkinson's diseases. Scientists, physicians, medical students, and all readers with an interest in brain function and its relationship to the immune system in health and disease will find this book a valuable resource. With general readers in mind, the authors provide a useful primer to explain scientific terms and concepts discussed in the book.-- Source other than Library of Congress.

Microglia are by far the best-characterized macrophages in the CNS, but non-parenchymal populations, such as those found in the meninges, are being increasingly studied. Prinz et al . review the ontogeny and functions of both parenchymal macrophages and non-parenchymal macrophages the CNS. Myeloid cells in the central nervous system (CNS) represent a heterogeneous class of innate immune cells that contribute to the maintenance of tissue homeostasis differentially during development and adulthood. The subsets of CNS myeloid cells identified so far, including parenchymal microglia and non-parenchymal meningeal, perivascular and choroid-plexus macrophages, as well as disease-associated monocytes, have classically been distinguished on the basis of their surface epitope expression, localization and morphology. However, studies using cell-specific targeting, in vivo imaging, single-cell expression analysis and other sophisticated tools have now increased the depth of knowledge of this immune-cell compartment and call for reevaluation of the traditional views on the origin, fate and function of distinct CNS myeloid subsets. The concepts of CNS macrophage biology that are emerging from these new insights have broad implications for the understanding and treatment of CNS diseases.

Nonfiction graphic novel explaining the physiology of the brain and describing theoretical and experimental developments that led to our present understanding.

Neuroinflammation plays an important role in the pathogenesis of various central nervous system (CNS) diseases. The NLRP3 inflammasome is an important intracellular multiprotein complex composed of the innate immune receptor NLRP3, the adaptor protein ASC, and the protease caspase-1. The activation of the NLRP3 inflammasome can induce pyroptosis and the release of the proinflammatory cytokines IL-1β and IL-18, thus playing a central role in immune and inflammatory responses. Recent studies have revealed that the NLRP3 inflammasome is activated in the brain to induce neuroinflammation, leading to further neuronal damage and functional impairment, and contributes to the pathological process of various neurological diseases, such as multiple sclerosis, Parkinson’s disease, Alzheimer’s disease, and stroke. In this review, we summarize the important role of the NLRP3 inflammasome in the pathogenesis of neuroinflammation and the pathological course of CNS diseases and discuss potential approaches to target the NLRP3 inflammasome for the treatment of CNS diseases.