Immunohistochemical labeling of ongoing axonal degeneration 10 days following cervical contusion spinal cord injury in the rat DOI Creative Commons
Anna Fusco, Sabhya Rana,

Marda L. Jorgenson

и другие.

Research Square (Research Square), Год журнала: 2024, Номер unknown

Опубликована: Окт. 11, 2024

Abstract Study Design: Experimental Animal Objective To continue validating an antibody which targets epitope of neurofilament light chain (NF-L) only available during neurodegeneration and to utilize the describe pattern axonal degeneration 10 days post-unilateral C4 contusion in rat. Setting: University Florida Methods Sprague Dawley rats received either a unilateral 150kdyn (n = 6; n 3 females, males) or laminectomy control surgery 5; males, 2 females). Ten following SCI laminectomy, spinal cords brainstems were processed for immunohistochemistry. Serial cord brainstem cross-sections stained with degeneration-specific NF-L (MCA-6H63) dual labeled against C-terminus portion (NF-L-Ct), label healthy axons, amyloid precursor protein (APP), considered current “gold standard” identifying degenerating axons. The ongoing was assessed. Results Spinal from injured had punctate MCA-6H63 positive fibers pathological appearance, loss anti-NF-L-Ct co-labeling, frequent colocalization APP. Immunopositive abundant rostral caudal lesion white matter tracts that would be disrupted by contusion. This staining not observed tissue. Conclusions labels axons offers promising tool quantify degeneration.

Язык: Английский

Neurofilaments as biomarkers in neurological disorders — towards clinical application DOI
Michael Khalil, Charlotte E. Teunissen, Sylvain Lehmann

и другие.

Nature Reviews Neurology, Год журнала: 2024, Номер 20(5), С. 269 - 287

Опубликована: Апрель 12, 2024

Язык: Английский

Процитировано

111
Neurofilament Light Chain Elevation and Disability Progression in Multiple Sclerosis DOI
Ahmed Abdelhak, Pascal Benkert,

Sabine Schaedelin

и другие.

JAMA Neurology, Год журнала: 2023, Номер 80(12), С. 1317 - 1317

Опубликована: Ноя. 6, 2023

Importance Mechanisms contributing to disability accumulation in multiple sclerosis (MS) are poorly understood. Blood neurofilament light chain (NfL) level, a marker of neuroaxonal injury, correlates robustly with disease activity people MS (MS); however, data on the association between NfL level and have been conflicting. Objective To determine whether when levels elevated context confirmed worsening (CDW). Design, Setting, Participants This study included 2 observational cohorts: results from Expression, Proteomics, Imaging, Clinical (EPIC) at University California San Francisco (since 2004) were Swiss Multiple Sclerosis Cohort (SMSC), multicenter 8 centers since 2012. Data extracted EPIC April 2022 (sampling July 1, 2004, December 20, 2016) SMSC June 6, 2012, September 2, 2021). The cohorts tertiary centers. All participants both available study, no eligible excluded or declined participate. Exposure Association z scores CDW. Main Outcome Measures CDW was defined as Expanded Disability Status Scale (EDSS) that after 6 more months classified into associated clinical relapses (CDW-R) independent (CDW-NR). Visits relation events CDW(−2) for visits preceding event, CDW(−1) directly CDW(event) first diagnosis EDSS increase, confirmation visit. Mixed linear Cox regression models used evaluate dynamics assess future CDW, respectively. Results A total 3906 (609 participants; median [IQR] age, 42.0 [35.0-50.0] years; 424 female [69.6%]) 8901 (1290 41.2 [32.5-49.9] 850 [65.9%]) included. In CDW-R (EPIC, 36 events; SMSC, 93 events), 0.71 (95% CI, 0.35-1.07; P < .001) units higher CDW-R(−1) 0.32 0.14-0.49; compared stable samples. elevation could be detected CDW-NR 191 342 events) CDW-NR(−2) (EPIC: 0.23; 95% 0.01-0.45; = .04; SMSC: 0.28; 0.18-0.37; CDW-NR(−1) 0.27; 0.11-0.44; .001; 0.09; 0-0.18; .06). Those findings replicated subgroup relapsing-remitting MS. Time-to-event analysis within approximately 1 year (in 1-2 years). Conclusions Relevance cohort documents occurrence advance may hint potential window ongoing dynamic central nervous system pathology precedes

Язык: Английский

Процитировано

42
Therapeutic potential of human microglia transplantation in a chimeric model of CSF1R-related leukoencephalopathy DOI Creative Commons
Jean Paul Chadarevian, Jonathan Hasselmann, Alina Lahian

и другие.

Neuron, Год журнала: 2024, Номер 112(16), С. 2686 - 2707.e8

Опубликована: Июнь 18, 2024

Microglia replacement strategies are increasingly being considered for the treatment of primary microgliopathies like adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP). However, available mouse models fail to recapitulate diverse neuropathologies reduced microglia numbers observed in patients. In this study, we generated a xenotolerant model lacking fms-intronic regulatory element (FIRE) enhancer within Csf1r, which develops nearly all hallmark pathologies associated ALSP. Remarkably, transplantation human induced pluripotent stem cell (iPSC)-derived microglial (iMG) progenitors restores homeostatic signature prevents development spheroids, white matter abnormalities, reactive astrocytosis, brain calcifications. Furthermore, CRISPR-corrected ALSP-patient-derived iMG reverses pre-existing astrogliosis, calcification pathologies. Together accompanying study by Munro colleagues, our results demonstrate utility FIRE mice ALSP provide compelling evidence that could offer promising new therapeutic strategy perhaps other microglia-associated neurological disorders.

Язык: Английский

Процитировано

23
Oligodendroglial fatty acid metabolism as a central nervous system energy reserve DOI Creative Commons
Ebrahim Asadollahi, Andrea Trevisiol, Aiman S. Saab

и другие.

Nature Neuroscience, Год журнала: 2024, Номер 27(10), С. 1934 - 1944

Опубликована: Сен. 9, 2024

Язык: Английский

Процитировано

19
Oligodendrocytes and myelin limit neuronal plasticity in visual cortex DOI Creative Commons
Wendy Xin, Megumi Kaneko, Richard H. Roth

и другие.

Nature, Год журнала: 2024, Номер 633(8031), С. 856 - 863

Опубликована: Авг. 21, 2024

Abstract Developmental myelination is a protracted process in the mammalian brain 1 . One theory for why oligodendrocytes mature so slowly posits that may stabilize neuronal circuits and temper plasticity as animals age 2–4 We tested this visual cortex, which has well-defined critical period experience-dependent 5 During adolescence, experience modulated rate of oligodendrocyte maturation cortex. To determine whether turn regulates plasticity, we genetically blocked differentiation adolescent mice. In adult mice lacking oligodendrogenesis, brief monocular deprivation led to significant decrease cortex responses deprived eye, reminiscent normally restricted adolescence. This enhanced functional was accompanied by greater turnover dendritic spines coordinated reductions spine size following deprivation. Furthermore, inhibitory synaptic transmission, gates at circuit level, diminished absence oligodendrogenesis. These results establish role shaping stabilization cortical support concept developmental acting brake on plasticity.

Язык: Английский

Процитировано

13
CSF neurofilament light chain profiling and quantitation in neurological diseases DOI Creative Commons
Claire A. Leckey, John B. Coulton, Tatiana A. Giovannucci

и другие.

Brain Communications, Год журнала: 2024, Номер 6(3)

Опубликована: Янв. 1, 2024

Abstract Neurofilament light chain is an established marker of neuroaxonal injury that elevated in CSF and blood across various neurological diseases. It increasingly used clinical practice to aid diagnosis monitor progression as outcome measure assess safety efficacy disease-modifying therapies the translational neuroscience field. Quantitative methods for neurofilament human biofluids have relied on immunoassays, which limited capacity describe structure protein how this might vary different neurodegenerative In study, we characterized quantified species neuroinflammatory diseases healthy controls using targeted mass spectrometry. We show quantitative immunoprecipitation–tandem spectrometry method developed study strongly correlates single-molecule array measurements broad spectrum was replicable centres. summary, created accurate cost-effective assay measuring a key biomarker research practice, can be easily multiplexed translated into laboratories screening monitoring disease or acute brain injury.

Язык: Английский

Процитировано

8
Head-to-head comparison of four plasma neurofilament light chain (NfL) immunoassays DOI
Susan Ashrafzadeh‐Kian, Daniel Figdore,

Bethany J. Larson

и другие.

Clinica Chimica Acta, Год журнала: 2024, Номер 561, С. 119817 - 119817

Опубликована: Июнь 14, 2024

Язык: Английский

Процитировано

5
Emerging Trends: Neurofilament Biomarkers in Precision Neurology DOI
Priti Sharma, Aditi Giri, Prabhash Nath Tripathi

и другие.

Neurochemical Research, Год журнала: 2024, Номер unknown

Опубликована: Сен. 30, 2024

Язык: Английский

Процитировано

5
Immunohistochemical labeling of ongoing axonal degeneration 10 days following cervical contusion spinal cord injury in the rat DOI
Anna Fusco, Sabhya Rana, Marda Jorgensen

и другие.

Spinal Cord, Год журнала: 2025, Номер unknown

Опубликована: Янв. 3, 2025

Язык: Английский

Процитировано

0
Neurofilament Light Chain under the Lens of Structural Mass Spectrometry DOI Creative Commons
Salomé Coppens, Dea Gogishvili,

Valentina Faustinelli

и другие.

ACS Chemical Neuroscience, Год журнала: 2025, Номер 16(2), С. 141 - 151

Опубликована: Янв. 2, 2025

Neurofilament light chain (NfL) is an early nonspecific biomarker in neurodegenerative diseases and traumatic brain injury, indicating axonal damage. This work describes the detailed structural characterization of a selected primary calibrator with potential to be used future reference measurement procedure (RMP) development for accurate quantification NfL. As part described workflow, sequence, higher-order structure as well solvent accessibility, hydrogen-bonding profile were assessed under three different conditions KPBS, artificial cerebrospinal fluid, fluid presence human serum albumin. The results revealed that NfL structurally heterogeneous protein, eliciting large conformational flexibility. Its ensemble changed when it was diluted aqueous buffer versus surrogate matrix, (aCSF), and/or aCSF Various regions protection deprotection protein head, central helical, tail domains experienced altered accessibility changes caused by identified. Moreover, interfacial residues, which may play role direct interaction between albumin, emerged from hydrogen–deuterium exchange mass spectrometry (HDX-MS). These data pinpointed distinct participate such interaction. Overall, critical quality attributes measurements are provided. findings will ultimately inform ongoing biochemical clinical assay procedures manufacturing practices, giving careful consideration during sample handling method development.

Язык: Английский

Процитировано

0