Nanomicellar formulation of coenzyme Q10 (Ubisol-Q10) effectively blocks ongoing neurodegeneration in the mouse 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine model: potential use as an adjuvant treatment in Parkinson's disease.

Although the support for the use of antioxidants, such as coenzyme Q(10) (CoQ(10)), to treat Parkinson's disease (PD) comes from the extensive scientific evidence, the results of conducted thus far clinical trials are inconclusive. It is assumed that the efficacy of CoQ(10) is hindered by insolubility, poor bioavailability, and lack of brain penetration. We have developed a nanomicellar formulation of CoQ(10) (Ubisol-Q(10)) with improved properties, including the brain penetration, and tested its effectiveness in mouse MPTP (1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine) model with the objectives to assess its potential use as an adjuvant therapy for PD.

Neuroprotective effects of GDNF-expressing human amniotic fluid cells.

Brain injury continues to be one of the leading causes of disability worldwide. Despite decades of research, there is currently no pharmacologically effective treatment for preventing neuronal loss and repairing the brain. As a result, novel therapeutic approaches, such as cell-based therapies, are being actively pursued to repair tissue damage and restore neurological function after injury.

Therapeutic potential of amniotic fluid-derived cells for treating the injured nervous system.

There is a need for improved therapy for acquired brain injury, which has proven resistant to treatment by numerous drugs in clinical trials and continues to represent one of the leading causes of disability worldwide. Research into cell-based therapies for the treatment of brain injury is growing rapidly, but the ideal cell source has yet to be determined. Subpopulations of cells found in amniotic fluid, which is readily obtained during routine amniocentesis, can be easily expanded in culture, have multipotent differentiation capacity, are non-tumourigenic, and avoid the ethical complications associated with embryonic stem cells, making them a promising cell source for therapeutic purposes.

Human amniotic fluid cells form functional gap junctions with cortical cells.

The usage of stem cells is a promising strategy for the repair of damaged tissue in the injured brain. Recently, amniotic fluid (AF) cells have received a lot of attention as an alternative source of stem cells for cell-based therapies. However, the success of this approach relies significantly on proper interactions between graft and host tissue.

Development of BMP7-producing human cells, using a third generation lentiviral gene delivery system.

Bone morphogenetic protein 7 (BMP7), a member of the transforming growth factor β (TGF-β) superfamily, plays important roles in the development of various tissues and organs in mouse and human. In particular, BMP7 is critical for the formation of the nervous system and it is considered to have therapeutic potential in brain injury and stroke. One approach to make BMP7 more suitable for therapeutic purposes is the development of efficient vectors that allow the consistent, reliable and cost-effective production of the BMP7 protein.

Detection of acute brain injury by Raman spectral signature.

Brain injury can lead to irreversible tissue loss and functional deficit along with significant health care costs. Raman spectroscopy can be used as a non-invasive technique to provide detailed information on the molecular composition of diseased and damaged tissues. This technique was used to examine acute mouse brain injury, focusing on the motor cortex, a region directly involved in controlling execution of movement.

Proteomic analysis of synaptosomal protein expression reveals that cerebral ischemia alters lysosomal Psap processing.

Cerebral ischemia (CI) induces dramatic changes in synaptic structure and function that precedes delayed post-ischemic neuronal death. Here, a proteomic analysis was used to identify the effects of focal CI on synaptosomal protein levels. Contralateral and ipsilateral synaptosomes, prepared from adult mice subjected to 60 min middle cerebral artery occlusion, were isolated following 3, 6 and 20 h of reperfusion.

Neuropilin 1 directly interacts with Fer kinase to mediate semaphorin 3A-induced death of cortical neurons.

Neuropilins (NRPs) are receptors for the major chemorepulsive axonal guidance cue semaphorins (Sema). The interaction of Sema3A/NRP1 during development leads to the collapse of growth cones. Here we show that Sema3A also induces death of cultured cortical neurons through NRP1.

Neuroregenerative strategies in the brain: emerging significance of bone morphogenetic protein 7 (BMP7).

Every year thousands of people suffer from brain injuries and stroke, and develop motor, sensory, and cognitive problems as a result of neuronal loss in the brain. Unfortunately, the damaged brain has a limited ability to enact repair and current modes of treatment are not sufficient to offset the damage. An extensive list of growth factors, neurotrophic factors, cytokines, and drugs has been explored as potential therapies.

Calpain cleavage of collapsin response mediator proteins in ischemic mouse brain.

Collapsin response mediator proteins (CRMPs) are important brain-specific proteins with distinct functions in modulating growth cone collapse and axonal guidance during brain development. Our previous studies have shown that calpain cleaves CRMP3 in the adult mouse brain during cerebral ischemia [S.T.

Cerebral ischemia causes dysregulation of synaptic adhesion in mouse synaptosomes.

Synaptic pathology is observed during hypoxic events in the central nervous system in the form of altered dendrite structure and conductance changes. These alterations are rapidly reversible, on the return of normoxia, but are thought to initiate subsequent neuronal cell death. To characterize the effects of hypoxia on regulators of synaptic stability, we examined the temporal expression of cell adhesion molecules (CAMs) in synaptosomes after transient middle cerebral artery occlusion (MCAO) in mice.

Role of Sox2 in the development of the mouse neocortex.

The mammalian neocortex is established from neural stem and progenitor cells that utilize specific transcriptional and environmental factors to create functional neurons and astrocytes. Here, we examined the mechanism of Sox2 action during neocortical neurogenesis and gliogenesis. We established a robust Sox2 expression in neural stem and progenitor cells within the ventricular zone, which persisted until the cells exited the cell cycle.

Derivatised alpha-tocopherol as a CoQ10 carrier in a novel water-soluble formulation.

We have derivatised alpha-tocopherol (vitamin E) to a water-soluble polyoxyethanyl-alpha - tocopheryl sebacate (PTS) and discovered that it formed a non-covalent complex with CoQ10 at a molar ratio of 2:1 (PTS-CoQ10). This complex was water-soluble and remained stable for extended periods of time. After oral delivery of the formulation into rats PTS was hydrolysed to vitamin E and elevated levels of both vitamin E and CoQ10 in blood plasma were detected within 1 h.

Absence of the transcription factor E2F1 attenuates brain injury and improves behavior after focal ischemia in mice.

Because of observations that cultured neurons from mice deficient in the transcription factor E2F1 exhibit resistance after treatment with a wide variety of cell-death inducers, the authors investigated whether resistance extended to a cerebral ischemic insult. No differences in cerebral blood flow or physiologic parameters were observed in the mutant E2F1 littermates after the focal ligation. After 2 hours of left middle cerebral artery occlusion and 1 day of reperfusion, a 33% smaller infarct (P < 0.

Characterization of cyclin D1 expression in a rat global model of cerebral ischemia.

During normal development of the central nervous system there is expression of cyclins that regulate the progression of cells through various stages of mitosis. Cyclins have also been implicated in neuronal degeneration and apoptosis in adult brain, especially cyclin D1 as it is permissive for the transition from growth phase to synthesis phase in mitotic cell division. There is controversy as to whether cyclin D1 expression increases in both in vitro and in vivo models of cerebral ischemia.

Decreased brain infarct following focal ischemia in mice lacking the transcription factor E2F1.

E2F1+/- mice subjected to 2 h middle cerebral artery occlusion developed an infarct of 77.0 +/- 3.2 mm3 (mean +/- s.