In vivo interrogation of central nervous system translatome by polyribosome fractionation.

Multiple processes are involved in gene expression including transcription, translation and stability of mRNAs and proteins. Each of these steps are tightly regulated, affecting the final dynamics of protein abundance. Various regulatory mechanisms exist at the translation step, rendering mRNA levels alone an unreliable indicator of gene expression.

The hematopoietic factor granulocyte-colony stimulating factor improves outcome in experimental spinal cord injury.

Granulocyte-colony stimulating factor (G-CSF) is a potent hematopoietic factor that drives differentiation of neutrophilic granulocytes. We have recently shown that G-CSF also acts as a neuronal growth factor, protects neurons in vitro and in vivo, and has regenerative potential in various neurological disease models. Spinal cord injury (SCI) following trauma or secondary to skeletal instability is a terrible condition with no effective therapies available at present.

CD95-ligand on peripheral myeloid cells activates Syk kinase to trigger their recruitment to the inflammatory site.

Injury to the central nervous system initiates an uncontrolled inflammatory response that results in both tissue repair and destruction. Here, we showed that, in rodents and humans, injury to the spinal cord triggered surface expression of CD95 ligand (CD95L, FasL) on peripheral blood myeloid cells. CD95L stimulation of CD95 on these cells activated phosphoinositide 3-kinase (PI3K) and metalloproteinase-9 (MMP-9) via recruitment and activation of Syk kinase, ultimately leading to increased migration.

The death receptor CD95 activates adult neural stem cells for working memory formation and brain repair.

Adult neurogenesis persists in the subventricular zone and the dentate gyrus and can be induced upon central nervous system injury. However, the final contribution of newborn neurons to neuronal networks is limited. Here we show that in neural stem cells, stimulation of the "death receptor" CD95 does not trigger apoptosis but unexpectedly leads to increased stem cell survival and neuronal specification.

Yes and PI3K bind CD95 to signal invasion of glioblastoma.

Invasion of surrounding brain tissue by isolated tumor cells represents one of the main obstacles to a curative therapy of glioblastoma multiforme. Here we unravel a mechanism regulating glioma infiltration. Tumor interaction with the surrounding brain tissue induces CD95 Ligand expression.

Manganese-enhanced magnetic resonance imaging for in vivo assessment of damage and functional improvement following spinal cord injury in mice.

In past decades, much effort has been invested in developing therapies for spinal injuries. Lack of standardization of clinical read-out measures, however, makes direct comparison of experimental therapies difficult. Damage and therapeutic effects in vivo are routinely evaluated using rather subjective behavioral tests.

Molecular targets in spinal cord injury.

The spinal cord can be compared to a highway connecting the brain with the different body levels lying underneath, with the axons being the ultimate carriers of the electrical impulse. After spinal cord injury (SCI), many cells are lost because of the injury. To reconstitute function, damaged axons from surviving neurons have to grow through the lesion site to their initial targets.

Neutralization of CD95 ligand promotes regeneration and functional recovery after spinal cord injury.

The clinical outcome of spinal cord injury (SCI) depends in part on the extent of secondary damage, to which apoptosis contributes. The CD95 and tumor necrosis factor (TNF) ligand/receptor systems play an essential role in various apoptotic mechanisms. To determine the involvement of these ligands in SCI-induced damage, we neutralized the activity of CD95 ligand (CD95L) and/or TNF in spinal cord-injured mice.