Drug delivery to the central nervous system is limited by the blood-brain barrier, which can be circumvented by local delivery. In applications of stroke therapy, for example, stimulation of endogenous neural stem/progenitor cells (NSPCs) by cyclosporin A (CsA) is promising. However, current strategies rely on high systemic drug doses to achieve small amounts of CsA in the brain tissue, resulti...

Spinal cord injury (SCI), resulting in para- and tetraplegia caused by the partial or complete disruption of descending motor and ascending sensory neurons, represents a complex neurological condition that remains incurable. Following SCI, numerous obstacles comprising of the loss of neural tissue (neurons, astrocytes, and oligodendrocytes), formation of a cavity, inflammation, loss of neuronal...

The use of stem cell technologies in retinal defect reparation therapy has produced beneficial results. Nowadays, numerous protocols exist which provide a neural differentiation of the stem cells transplanted into the retina. However, questions concerning the functional replacement of the missing retinal neurons by transplanted cells thus far remain unanswered. The organotypic culture protocol ...

Neural stem/progenitor cells (NSPCs) generate new neurons throughout life in the mammalian hippocampus. Newborn granule cells mature over several weeks to functionally integrate into the pre-existing neural circuitry. Even though an increasing number of genes that regulate neuronal polarization and neurite extension have been identified, the cellular mechanisms underlying the extension of neuri...

White matter dysfunction is an important part of many CNS disorders including multiple sclerosis (MS) and vascular dementia. Within injured areas, myelin loss and oligodendrocyte death may trigger endogenous attempts at regeneration. However, during disease progression, remyelination failure may eventually occur due to impaired survival/proliferation, migration/recruitment, and differentiation ...

Phytochelatin synthase (PCS) uses the substrates glutathione (GSH, γGlu-Cys-Gly) and a cadmium (Cd)-bound GSH (Cd∙GS2) to produce the shortest phytochelatin product (PC2, (γGlu-Cys)2-Gly) through a ping-pong mechanism. The binding of the 2 substrates to the active site, particularly the second substrate binding site, is not well-understood. In this study, we generated a structural model of the ...

The life-long generation of new neurons from radial glia-like neural stem cells (NSCs) is achieved through a stereotypic developmental sequence that requires precise regulatory mechanisms to prevent exhaustion or uncontrolled growth of the stem cell pool. Cellular metabolism is the new kid on the block of adult neurogenesis research and the identity of stage-specific metabolic programs and thei...

Ischemic stroke causes transient increase of neural stem and progenitor cell (NSPC) proliferation in the subventricular zone (SVZ), and migration of newly formed neuroblasts toward the damaged area where they mature to striatal neurons. The molecular mechanisms regulating this plastic response, probably involved in structural reorganization and functional recovery, are poorly understood. The ad...

In the stem cell field there is a lack of non invasive and fast methods to identify stem cell's metabolic state, differentiation state and cell-lineage commitment. Here we describe a label-free method that uses NADH as an intrinsic biomarker and the Phasor approach to Fluorescence Lifetime microscopy to measure the metabolic fingerprint of cells. We show that different metabolic states are rela...

Neural stem/progenitor cells (NPSCs) express receptors for many inflammatory cytokines, with varying effects on differentiation and proliferation depending on the stage of development and the milieu of inflammatory mediators. In primary neurons and astrocytes, we recently showed that interferon gamma (IFNγ), a potent antiviral cytokine that is required for the control and clearance of many cent...