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

et al.

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 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.

Language: Английский

EEG hyperexcitability and hyperconnectivity linked to GABAergic inhibitory interneuron loss following traumatic brain injury DOI Creative Commons
Hazel G May,

Konstantinos Tsikonofilos,

Cornelius K. Donat

et al.

Brain Communications, Journal Year: 2024, Volume and Issue: 6(6)

Published: Jan. 1, 2024

Abstract Traumatic brain injury represents a significant global health burden and has the highest prevalence among neurological disorders. Even mild traumatic can induce subtle, long-lasting changes that increase risk of future neurodegeneration. Importantly, this be challenging to detect through conventional assessment. This underscores need for more sensitive diagnostic tools, such as electroencephalography, uncover opportunities therapeutic intervention. Progress in field been hindered by lack studies linking mechanistic insights at microscopic level from animal models macroscale phenotypes observed clinical imaging. Our study addresses gap investigating rat model blast using both immunohistochemical staining inhibitory interneurons translationally relevant electroencephalography recordings. Although we no pronounced effects immediately post-injury, chronic time points revealed broadband hyperexcitability increased connectivity, accompanied decreased density interneurons. pattern suggests disruption balance between excitation inhibition, providing crucial link cellular mechanisms hallmarks injury. findings have implications diagnosis, monitoring, treatment The emergence abnormalities points, despite absence immediate effects, highlights importance long-term monitoring patients. decrease interneuron offers potential mechanism underlying may represent target demonstrates value combining cellular-level analysis with neurophysiological recordings elucidate pathophysiology Future research should focus on translating these human exploring strategies targeting excitation-inhibition imbalance

Language: Английский

Citations

1
Adolescent oligodendrogenesis and myelination restrict experience-dependent neuronal plasticity in adult visual cortex DOI Creative Commons
Wendy Xin, Megumi Kaneko, Richard H. Roth

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Sept. 30, 2023

ABSTRACT BACKGROUND Developmental myelination is a protracted process in the mammalian brain. One theory for why oligodendrocytes mature so slowly posits that may stabilize neuronal circuits and temper plasticity as animals age. We tested this hypothesis visual cortex, which has well-defined critical period experience-dependent plasticity. OBJECTIVES/METHODS To prevent myelin progression, we conditionally deleted Myrf, transcription factor necessary oligodendrocyte maturation, from precursor cells (Myrf cKO) adolescent mice. induce plasticity, adult control Myrf cKO mice were monocularly deprived by eyelid suture. Functional structural cortex assessed vivo intrinsic signal optical imaging longitudinal two photon of dendritic spines, respectively. RESULTS During adolescence, experience modulated rate maturation cortex. deletion precursors during adolescence led to inhibition persisted into adulthood. Following monocular deprivation, activity response stimulation eye remained stable mice, expected post-critical animals. By contrast, responses decreased significantly following deprivation reminiscent observed Furthermore, neurons had fewer spines higher level spine turnover. Finally, induced spatially coordinated size decreases cKO, but not control, CONCLUSIONS These results demonstrate role shaping stabilization cortical support concept acting brake on development.

Language: Английский

Citations

2
Neurofilaments in neurologic disease DOI
Christina Mousele, David W. Holden, Sharmilee Gnanapavan

et al.

Advances in clinical chemistry, Journal Year: 2024, Volume and Issue: unknown, P. 65 - 128

Published: Jan. 1, 2024

Language: Английский

Citations

0
Multi-peptide characterization of plasma neurofilament light chain in preclinical and mild Alzheimer’s disease DOI Creative Commons
John B. Coulton, Yingxin He, Nicolas R. Barthélemy

et al.

Brain Communications, Journal Year: 2024, Volume and Issue: 6(4)

Published: Jan. 1, 2024

Although neurofilament light chain is a well-known marker of neuronal damage, its characterization at the proteoform level underdeveloped. Here, we describe new method to profile and quantify in plasma peptide level, using three in-house monoclonal antibodies targeting distinct protein domains nano-liquid chromatography coupled high-resolution tandem mass spectrometry. This study profiled compared CSF 102 older individuals (73.9 ± 6.3 years old), 37 which had clinical dementia rating greater than 0. We observed elevated preclinical Alzheimer's disease for two measures (NfL101 NfL324) seven (NfL92, NfL101, NfL117, NfL137, NfL148, NfL165 NfL530). found five peptides NfL324 NfL530) significantly associated with age (NfL148 body index.

Language: Английский

Citations

0
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

et al.

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 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.

Language: Английский

Citations

0