Stretch-Induced Injury Alters Mitochondrial Membrane Potential and Cellular ATP in Cultured Astrocytes and Neurons

Strain rate-dependent induction of reactive astrogliosis and cell death in three-dimensional neuronal–astrocytic co-cultures

“…Similarly, our outcome measures were based on cumulative culture alterations, and we cannot rule out cell-specific changes following loading that did not alter aggregate outcome measures. Nonetheless, the relative alterations in cell viability following the loading regimes used in this study are consistent with those following both in vivo and in vitro models of neural trauma (Gennarelli et al, 1982;Ellis et al, 1995;Meaney et al, 1995;Ahmed et al, 2000). Strain rate-dependent responses to mechanical loading have previously been reported for neural cells (Ellis et al, 1995;Cargill and Thibault, 1996;LaPlaca et al, 1997;Geddes and Cargill, 2001;LaPlaca et al, 2005), but this is the first report of such a response in neural co-cultures based on 3-D biomechanical inputs.…”

Ionizing radiation modulates vascular endothelial growth factor (VEGF) expression through multiple mitogen activated protein kinase dependent pathways

“…Generation of primary astrocytes Primary astrocytes were isolated and prepared from the brains of Fisher 344 rats as described in Ahmed et al (2000). Cells were cultured for 3 weeks prior to study.…”

Neuroprotective roles of the P2Y2 receptor

“…P2Y 2 and P2Y 6 receptors have been suggested to play complementary roles in the regulation of apoptosis, since P2Y 6 R activation inhibits tumor necrosis factor-α (TNF-α) receptor signaling [78] and P2Y 2 R activation upregulates anti-apoptotic proteins [79] to promote survival mechanisms in astrocytic cells. P2YR functions associated with the pathogenesis of inflammation in the CNS, a process involving astrocyte and microglial cell proliferation and migration to a site of injury (i.e., gliosis), can be induced by a variety of conditions (e.g., oxidative stress or excessive β-amyloid (Aβ) peptide production) that stimulate the release of proinflammatory mediators, including cytokines [15,75,76,[80][81][82][83][84][85][86]. Among these mediators, ATP and other nucleotides also can be released into the extracellular space due to cell damage, oxidative stress, hypoxia, ischemia, or mechanical stress [17,[81][82][83][84], whereupon the nucleotides activate P2X and P2Y receptors expressed in surrounding cells.…”

“…P2YR functions associated with the pathogenesis of inflammation in the CNS, a process involving astrocyte and microglial cell proliferation and migration to a site of injury (i.e., gliosis), can be induced by a variety of conditions (e.g., oxidative stress or excessive β-amyloid (Aβ) peptide production) that stimulate the release of proinflammatory mediators, including cytokines [15,75,76,[80][81][82][83][84][85][86]. Among these mediators, ATP and other nucleotides also can be released into the extracellular space due to cell damage, oxidative stress, hypoxia, ischemia, or mechanical stress [17,[81][82][83][84], whereupon the nucleotides activate P2X and P2Y receptors expressed in surrounding cells. Several studies have proposed the involvement of P2Rs, including the P2X7R and P2Y 2 R, in proinflammatory responses mediated by glial cells that are associated with neurodegenerative diseases [15,20,57,75,76,85].…”