Hurtado O, Lizasoain I, Fernandez-Tome P, Alvarez-Barrientos A, Leza JC, Lorenzo P, Moro MATACE/ADAM17-TNF-alpha pathway in rat cortical cultures after exposure to oxygen-glucose deprivation or glutamate. J Cereb Blood Flow Metab 22:576-585
The role of the tumor necrosis factor (TNF)-alpha convertase (TACE/ADAM17) in the adult nervous system remains poorly understood. The authors have previously demonstrated that TACE is upregulated in rat forebrain slices exposed to oxygen-glucose deprivation (OGD). They have now used rat mixed cortical cultures exposed to OGD or glutamate to study (1) TACE expression and localization, and (2) the effects of TNF-alpha release on cell viability. OGD-or glutamate-caused TNF-alpha release, an effect that was blocked by the TACE inhibitor BB3103 (BB) (0.1-1 micromol/L; control: 1.67 +/- 0.59; OGD: 6.59 +/- 1.52; glutamate: 3.38 +/- 0.66; OGD +/- BB0.1: 3.23 +/- 0.67; OGD +/- BB1: 1.33 +/- 0.22 pg/mL, n = 6, P < 0.05). Assay of TACE activity as well as Western blot showed that TACE expression is increased in OGD-or glutamate-exposed cells. In control cultures, TACE immunoreactivity was present in some microglial cells, whereas, after OGD or glutamate, TACE immunostaining appeared in most microglial cells and in some astrocytes. Conversely, BB3103 (0.1 micromol/L) caused apoptosis after glutamate exposure as shown by annexin and Hoechst 33342 staining and caspase-3 activity, an effect mimicked by the proteasome inhibitor MG-132 (caspase activity: glutamate: 5.1 +/- 0.1; glutamate + BB: 7.8 +/- 0.8; glutamate + MG: 11.9 +/- 0.5 pmol. min(-1) mg(-1) protein, n = 4, P < 0.05), suggesting that translocation of the transcription factor NF-kappaB mediates TNF-alpha-induced antiapoptotic effect. Taken together, these data demonstrate that, in rat mixed neuronal-glial cortical cultures exposed to OGD or glutamate, (1) TACE/ADAM17 activity accounts for the majority of TNF-alpha shedding, (2) an increase in glial TACE expression contributes to the rise in TNF-alpha, and (3) TNF-alpha release in this setting inhibits apoptosis via activation of the transcription factor NF-kappaB.
"Ventricular zone neurogenesis peaks at E14 and recedes at E17 in rats. In contrast, cells originating from the subventricular zone at late embryonic days and early postnatal days (rat E17 to postnatal day [P]14) are destined predominantly for glial lineages29,30). "
[Show abstract][Hide abstract] ABSTRACT: Hypoxic-ischemic encephalopathy is an important cause of neonatal mortality, as this brain injury disrupts normal mitochondrial respiratory activity. Carnitine plays an essential role in mitochondrial fatty acid transport and modulates excess acyl coenzyme A levels. In this study, we investigated whether treatment of primary cultures of rat cortical neurons with L-carnitine was able to prevent neurotoxicity resulting from oxygen-glucose deprivation (OGD).
Cortical neurons were prepared from Sprague-Dawley rat embryos. L-Carnitine was applied to cultures just prior to OGD and subsequent reoxygenation. The numbers of cells that stained with acridine orange (AO) and propidium iodide (PI) were counted, and lactate dehydrogenase (LDH) activity and reactive oxygen species (ROS) levels were measured. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and the terminal uridine deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling assay were performed to evaluate the effect of L-carnitine (1 µM, 10 µM, and 100 µM) on OGD-induced neurotoxicity.
Treatment of primary cultures of rat cortical neurons with L-carnitine significantly reduced cell necrosis and prevented apoptosis after OGD. L-Carnitine application significantly reduced the number of cells that died, as assessed by the PI/AO ratio, and also reduced ROS release in the OGD groups treated with 10 µM and 100 µM of L-carnitine compared with the untreated OGD group (P<0.05). The application of L-carnitine at 100 µM significantly decreased cytotoxicity, LDH release, and inhibited apoptosis compared to the untreated OGD group (P<0.05).
L-Carnitine has neuroprotective benefits against OGD in rat primary cortical neurons in vitro.
Korean Journal of Pediatrics 07/2012; 55(7):238-48. DOI:10.3345/kjp.2012.55.7.238
"At the initiation of angiogenesis, pericytes are involved in induction of endothelial activation accompanied by augmentation of a variety of proteases , adhesion molecules and proteoglycans . Astrocyte expression of tumor necrosis factor converting enzyme (TACE/ADAM-17) may facilitate pericyte PDGFβR signaling mechanisms . Alternatively, at maturation the recruitment of pericytes to the newly-formed endothelial tubes is accompanied by silencing of MMP activities . "
[Show abstract][Hide abstract] ABSTRACT: The French scientist Charles Benjamin Rouget identified the pericyte nearly 140 years ago. Since that time the role of the pericyte in vascular function has been difficult to elucidate. It was not until the development of techniques to isolate and culture pericytes that scientists have begun to understand the true impact of this unique cell in the maintenance of tissue homeostasis. In the brain the pericyte is an integral cellular component of the blood-brain barrier and, together with other cells of the neurovascular unit (endothelial cells, astrocytes and neurons) the pericyte makes fine-tuned regulatory adjustments and adaptations to promote tissue survival. These regulatory changes involve trans-cellular communication networks between cells. In this review we consider evidence for cell-to-cell crosstalk between pericytes and astrocytes during development and in adult brain.
Fluids and Barriers of the CNS 01/2011; 8(1):8. DOI:10.1186/2045-8118-8-8
"of trauma exhibited a significant reduction in motor disturbances, indicates that increased levels of TNF-α at the site of injury may be a cause, rather than an effect, of the SCI induced by compressive trauma (Taoka et al. 1998). Interestingly, contrary to most report, there are certain documented evidences of its ameliorating potentials in CNS injury (Hurtado et al. 2002, Pradillo et al. 2005, for review see: Figiel 2008). A recent study however, ascribed to it, a dual role; depending on the phase of injury: overexpression of TNF-α is deleterious in the acute phase, but beneficial in the chronic phase in the response to SCI (Chi et al. 2010). "
[Show abstract][Hide abstract] ABSTRACT: The pathophysiology of acute spinal cord injury (SCI) involves primary and secondary mechanisms of injury. Though both mechanisms are involved in the neurological dysfunction in SCI most research however has focused on understanding the pathophysiology of the secondary damage and reducing the amount of delayed cell loss following SCI. Research has revealed extensive therapeutic windows in secondary injury mechanisms that could be manipulated by appropriate exogenous interventions. In contrast, primary injury to the cord happens unexpectedly, and it is associated with inevitable delays; ranging from several hours to days before care intervention is administered. Therefore, apart from achieving patient's stabilization, the therapeutic window in the primary phase of injury is essentially obliterated, and consequently inaccessible for specialized. Coupled to this, the exacerbating effect of secondary injury mechanisms has generally commenced before the specialist intervention. Hence, knowledge of secondary injury mechanisms and their intricacies are invaluable requisite for any tailored therapeutic strategy in the persistent search for a cure of SCI. There are about 25 well-established secondary injury mechanisms in SCI, and are found in bits or clusters in literature. A vast number of these articles are not open access. Besides, articles with a comprehensive catalog of these mechanisms are not readily available. This article has cataloged over twenty five identified secondary mechanisms of injury in the spinal cord in an open access portal, and is particularly versatile for starters in spinal cord injury research.
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