Abstract An understanding of the regulators neurogenesis in normal and diseased brain is necessary order to recruit endogenously produced neural precursors for cell replacement neurodegenerative disorders such as Parkinson's disease. The location dopaminergic projections from midbrain neostriatum nucleus accumbens overlaps with most active region adult brain, subventricular zone anterior lateral ventricle. This suggests that dopamine may contribute regulation niche neurogenesis. Here, we...

We have investigated the neuroprotective effects of recombinant human ciliary neurotrophic factor (CNTF) for injured dopaminergic neurons adult rat substantia nigra compacta. Fourteen days after a unilateral transection nigrostriatal pathway two-thirds (identified by retrograde labeling) had degenerated. In sharp contrast, 73% (a few cases, > 90%) this cell loss was prevented continuous infusion CNTF close to neurons. However, did not prevent disappearance transmitter-synthesizing enzyme...

The functions of the low-affinity p75 nerve growth factor receptor (p75 NGFR ) in central nervous system were explored vivo. In normal mice, approximately 25 percent cholinergic basal forebrain neurons did not express TrkA and died between postnatal day 6 15. This loss occur -deficient mice or systemically injected with a -inhibiting peptide. Control, but -deficient, also had fewer striatal interneurons. Apparently, mediates apoptosis these developing absence TrkA, modulation can promote...

Injured adult mammalian axons are unable to regenerate spontaneously in the central nervous tissue. This study investigated two rat models effects of nerve growth factor (NGF) on capacity primary sensory back into spinal cord. Sensory fibers were conditioned by transection peripheral 1 week prior experiment and identified anterograde tracing with cholera toxin B subunit injected sciatic nerve. In first model, a predegenerated autologous graft was implanted as bridge for transected resection...

Neurogenesis continues in the adult forebrain subventricular zone (SVZ) and dentate gyrus of hippocampal formation. Degeneration dopaminergic projections Parkinson's disease animals reduces, whereas ciliary neurotrophic factor (CNTF) promotes, neurogenesis. We tested whether system promotes neurogenesis through CNTF. Astrocytes SVZ expressed CNTF were close to terminals. Dopaminergic denervation mice reduced mRNA by ∼60%, systemic treatment with D 2 agonist quinpirole increased formation,...

Abstract Two rabbit polyclonal antibodies were raised against synthetic peptides corresponding to residue numbers 45–59 and 181–200 of rat ciliary neuronotrophic factor (CNTF). The resulting purified by affinity chromatography both reacted enzyme‐linked immunoassay (ELISA) immunoblotting with sciatic nerve CNTF. anti‐CNTF peptide used immunostain sections adult nerve, previously known as the richest tissue source By light microscopy appeared stain exclusively Schwann cells axons did so same...

Abstract Discrete regions of the adult CNS, including subventricular zone (SVZ), do retain capacity for neurogenesis. These progenitor cells may represent a potential new source replacement therapies in neuroregenerative diseases. An understanding microenvironmental signals regulating neurogenesis brain would facilitate development such therapeutic approaches. A particularly strong expression dopamine D 3 receptor mRNA occurs proliferative SVZ during prenatal and early postnatal ontogeny....

We have investigated the effects of nerve growth factor (NGF), brain-derived neurotrophic (BDNF), and neurotrophin-3 (NT-3) on intraspinal regeneration anterogradely labeled axotomized ascending primary sensory fibers in adult rat. These were allowed to grow across a predegenerated peripheral graft back into thoracic spinal cord. In control animals that had been infused with vehicle for two weeks dorsal column, 3 mm rostral graft, essentially no extended from The number end was not...

The well-documented but little-understood failure of lengthy axonal regeneration after injury the adult mammalian CNS may be caused by an insufficient availability local growth-promoting factors. If so, identifying and supplying missing factors result in better central regeneration. This hypothesis was tested rat model which peripheral nerve grafts were placed into a lesion cavity between septum hippocampal formation. Continuous infusion growth factor (NGF) dorsal tissue dramatically...

Abstract After traumatic spinal cord injury (SCI), disruption and plasticity of the microvasculature within injured tissue contribute to pathological cascades associated with evolution both primary secondary injury. Conversely, preserved vascular function most likely results in sparing subsequent functional recovery. It has been difficult identify subclasses damaged or regenerating blood vessels at cellular level. Here, adult mice received a single intravenous injection Griffonia...

Blood vessel loss and inflammation cause secondary degeneration following spinal cord injury. Angiopoietin-1 through the Tie2 receptor, other ligands αvβ3 integrin, promote endothelial cell survival during developmental or tumour angiogenesis. Here, daily intravenous injections with an αvβ3-binding peptide named C16 angiopoietin-1 mimetic a contusion at thoracic level 9 in mice rescued epicentre blood vessels, white matter locomotor function, reduced detrimental inflammation. Preserved...

STAT3 is increasingly becoming known for its non-transcriptional regulation of mitochondrial bioenergetic function upon activation S727 residue (S727-STAT3). Lengthy dysfunction can lead to cell death. We tested whether an integrin-FAK-STAT3 signaling pathway we recently discovered regulates and survival, treatments thereof.Cultured mouse brain bEnd5 endothelial cells were treated with integrin, FAK or inhibitors, siRNA, as well integrin activators. null transfected mutant plasmids. Outcome...

We found that blood vitronectin (VTN) leaks into the brain and exacerbates tissue loss after stroke by increasing pro-inflammatory IL-6 expression in female, but not male, mice. VTN signals through integrins downstream focal adhesion kinase (FAK). Here, a two day systemic treatment with small molecule FAK inhibitor starting 6 h middle cerebral artery occlusion reduced ipsilateral injury size ∼40–45% at 7 14 d, as well inflammation motor dysfunction wild-type inhibition also injured female...

The effect of intraspinally implanted predegenerated peripheral nerve grafts and/or conditioning lesions on the regenerative capacity central ascending sensory axons was investigated in adult rat. Regenerating fibers were analyzed after their transganglionic labeling with cholera toxin B subunit, usually 1 month implantation. A lesion (transection tibial and peroneal nerve) caused a fivefold increase number within fresh graft when applied day grafting sevenfold week before. In latter case,...

Abstract The role of nerve growth factor (NGF) as a target derived neurotrophic agent for specific cell populations in the peripheral nervous system has been well documented and much evidence suggests that NGF may serve similar CNS supporting cholinergic neurons basal forebrain. Previous attempts to localize by immunocytochemical methods, however, have not yielded confirming regional distribution expected based upon reported levels extractable NGF. In present study, affinity purified...