Translational value of choroid plexus imaging for tracking neuroinflammation in mice and humans.
Neuroinflammation is a pathophysiological hallmark of multiple sclerosis and has a close mechanistic link to neurodegeneration. Although this link is potentially targetable, robust translatable models to reliably quantify and track neuroinflammation in both mice and humans are lacking. The choroid plexus (ChP) plays a pivotal role in regulating the trafficking of immune cells from the brain parenchyma into the cerebrospinal fluid (CSF) and has recently attracted attention as a key structure in the initiation of inflammatory brain responses. In a translational framework, we here address the integrity and multidimensional characteristics of the ChP under inflammatory conditions and question w…
Resolving the transcriptional transitions associated with oligodendrocyte generation from adult neural stem cells by single cell sequencing
AbstractThe subventricular zone (SVZ) is the largest neurogenic niche in the adult forebrain. Notably, neural stem cells (NSCs) of the SVZ generate not only neurons, but also oligodendrocytes, the myelin-forming cells of the central nervous system. Transcriptomic studies have provided detailed knowledge of the molecular events that regulate neurogenesis, but little is understood about adult oligodendrogenesis from SVZ-NSCs. To address this, we performed in-depth single-cell transcriptomic analyses to resolve the major differences in neuronal and oligodendroglial lineages derived from the adult SVZ. A hallmark of adult oligodendrogenesis was the stage-specific expression of transcriptional m…
Taking Advantage of Nature’s Gift: Can Endogenous Neural Stem Cells Improve Myelin Regeneration?
Irreversible functional deficits in multiple sclerosis (MS) are directly correlated to axonal damage and loss. Neurodegeneration results from immune-mediated destruction of myelin sheaths and subsequent axonal demyelination. Importantly, oligodendrocytes, the myelinating glial cells of the central nervous system, can be replaced to some extent to generate new myelin sheaths. This endogenous regeneration capacity has so far mainly been attributed to the activation and recruitment of resident oligodendroglial precursor cells. As this self-repair process is limited and increasingly fails while MS progresses, much interest has evolved regarding the development of remyelination-promoting strateg…
Cortical gene expression in spinal cord injury and repair: insight into the functional complexity of the neural regeneration program
Traumatic spinal cord injury (SCI) results in the formation of a fibrous scar acting as a growth barrier for regenerating axons at the lesion site. We have previously shown (Klapka et al., 2005) that transient suppression of the inhibitory lesion scar in rat spinal cord leads to long distance axon regeneration, retrograde rescue of axotomized cortical motoneurons, and improvement of locomotor function. Here we applied a systemic approach to investigate for the first time specific and dynamic alterations in the cortical gene expression profile following both thoracic SCI and regeneration-promoting anti-scarring treatment (AST). In order to monitor cortical gene expression we carried out micr…