Neuronal death and survival in two models of hypoxic-ischemic brain damage

Walton, M.; Connor, Bronwen; Lawlor, P.; Young, Deborah; Sirimanne, Ernest; Gluckman, Peter D.; Cole, Gregory M.; Dragunow, Michael

doi:10.1016/s0165-0173(98)00053-8

Cited by 154 publications

(89 citation statements)

References 357 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In the context of the physiological role of BDNF, this apparent 'loss of function' is expected; increased BDNF is associated with activity, 40,41 cell survival, [42][43][44] learning and memory, 45 synaptic plasticity, 46,47 increased synthesis of mRNA and other processes that can be looked upon as 'positive' cellular events. Loss of BDNF would therefore be expected to decrease the expression of genes that mediate these effects.…”

Section: Discussionmentioning

confidence: 99%

Specificity and timing of neocortical transcriptome changes in response to BDNF gene ablation during embryogenesis or adulthood

et al. 2006

View full text Add to dashboard Cite

Section: Discussionmentioning

confidence: 99%

Specificity and timing of neocortical transcriptome changes in response to BDNF gene ablation during embryogenesis or adulthood

et al. 2006

View full text Add to dashboard Cite

“…When used in conjunction with propidium iodide exclusion to establish membrane integrity, it indicates cells undergoing apoptosis (34,35). In addition, we used the TUNEL technique to label DNA fragments at the 3Ј-OH DNA and, thus, identify nuclear DNA that is cleaved by endonucleases (35). Fig.…”

Section: Neuronal Death In Neuron/microglial Co-cultures Exposed Tomentioning

confidence: 99%

Mechanisms Underlying Neuronal Death Induced by Chromogranin A-activated Microglia

Ciesielski-Treska¹,

Ulrich²,

Chasserot‐Golaz³

et al. 2001

Journal of Biological Chemistry

View full text Add to dashboard Cite

The neurotoxic effects of activated microglia in neurodegenerative diseases are well established. We recently provided evidence that chromogranin A (CGA), a multifunctional protein localized in dystrophic neurites and in senile plaques, induces an activated phenotype and secretion of neurotoxins by rat microglia in culture. In the present study, we focused on the mechanisms underlying neuronal degeneration triggered by CGAactivated microglia. We found that neuronal death exhibits apoptotic features, characterized by the externalization of phosphatidylserine and the fragmentation of DNA. Microglial neurotoxins markedly stimulate the phosphorylation and activity of neuronal p38 mitogenactivated protein kinase and provoke the release of mitochondrial cytochrome c, which precedes apoptosis. Inhibition of p38 kinase with SB 203580 partially protects neurons from death induced by CGA-activated microglia. Furthermore, neurons are also protected by Fas-Fc, which antagonizes the interactions between the death receptor Fas and its ligand FasL and by cell-permeable peptides that inhibit caspases 8 and 3. Thus, CGA triggers the release of microglial neurotoxins that mobilize several death-signaling pathways in neurons. Our results further support the idea that CGA, which is upregulated in many neuropathologies, represents a potent endogeneous inflammatory factor possibly responsible for neuronal degeneration.

show abstract

“…The outcome after brain injury depends on the balance between mechanisms of injury and protection (Walton et al, 1999). In addition, it has recently been shown that the juvenile and adult brain can generate new neurons through proliferation of progenitor cells, and thus might help to repair brain damage (Arvidsson et al, 2002;Bartley et al, 2005;Daval et al, 2004;Eriksson et al, 1998;Plane et al, 2004;Scheepens et al, 2003;Sun et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

Less Neurogenesis and Inflammation in the Immature than in the Juvenile Brain after Cerebral Hypoxia-Ischemia

Qiu

Zhu

Wang

et al. 2006

J Cereb Blood Flow Metab

View full text Add to dashboard Cite

The effects of hypoxia-ischemia (HI) on proliferation and differentiation in the immature (postnatal day 9) and juvenile (postnatal day 21) mouse hippocampus were investigated by injecting bromodeoxyuridine (50 mg/kg) daily for 7 days after the insult and evaluating the labeling 5 weeks after HI. Phenotypic differentiation was evaluated using NeuN, Iba1, APC, and S100b as markers of neurons, microglia, oligodendrocytes, and astrocytes, respectively. The basal proliferation, in particular neurogenesis, was higher in the immature than in the juvenile hippocampus. Hypoxiaischemia did not increase neurogenesis significantly in the immature dentate gyrus (DG), but it increased several-fold in the juvenile brain, reaching the same level as in the normal, noninjured immature brain. This suggests that the immature hippocampus is already working at the top of its proliferative capacity and that even though basal neurogenesis decreased with age, the injuryinduced generation of new neurons in the juvenile hippocampus could not increase beyond the basal level of the immature brain. Generation of glial cells of all three types after HI was significantly more pronounced in the cornu ammonis of the hippocampus region of the juvenile hippocampus. In the DG, only microglia production was greater in the juvenile brain. Increased microglia proliferation correlated with increased levels of the proinflammatory cytokines MCP-1 and IL-18 3 days after HI, indicating that the inflammatory response is stronger in the juvenile hippocampus. In summary, contrary to what has been generally assumed, our results indicate that the juvenile brain has a greater capacity for neurogenesis after injury than the immature brain.

show abstract

Neuronal death and survival in two models of hypoxic-ischemic brain damage

Cited by 154 publications

References 357 publications

Specificity and timing of neocortical transcriptome changes in response to BDNF gene ablation during embryogenesis or adulthood

Specificity and timing of neocortical transcriptome changes in response to BDNF gene ablation during embryogenesis or adulthood

Mechanisms Underlying Neuronal Death Induced by Chromogranin A-activated Microglia

Less Neurogenesis and Inflammation in the Immature than in the Juvenile Brain after Cerebral Hypoxia-Ischemia

Contact Info

Product

Resources

About