Evidence for platelet-activating factor as a novel mediator in experimental stroke in rabbits.

Lindsberg, Perttu J.; Yue, Tian‐Li; Frerichs, Kai U.; Hallenbeck, John M.; Feuerstein, Giora

doi:10.1161/01.str.21.10.1452

Cited by 100 publications

(36 citation statements)

References 37 publications

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“…The involvement of PAF in the development of various CNS disorders, such as cerebral ischemia, 5,6 brain injury, 6 subarachnoid hemorrhage, 20 inflammation, 4 panic disorders, 3 and spinal cord ischemia, 21 has been demonstrated previously. Because selective PAF receptor antagonists ameliorated the brain damage after cerebral infarction, 5,6 activation of the PAF-PAF receptor signaling system appears to play a critical role in the occurrence and progression of neuronal injury induced by cerebral ischemia.…”

Section: Discussionmentioning

confidence: 75%

Neuroprotective Role of Transgenic PAF-Acetylhydrolase II in Mouse Models of Focal Cerebral Ischemia

Umemura

Kato

Hirashima

et al. 2007

Stroke

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Background and Purpose-Platelet-activating factor (PAF) and oxidized unsaturated free fatty acids have been postulated to aggravate neuronal damage in the postischemic brain. Type II PAF-acetylhydrolase (PAF-AH II) not only terminates signals by PAF by its PAF-hydrolyzing activity but also protects cells against oxidative stress. We examined whether PAF-AH II can rescue cerebral neurons against ischemic insults. Methods-Transgenic mice overexpressing human PAF-AH II in neurons were generated and enzyme expressions were examined biochemically and histochemically. The mice were subjected to 60 minutes of transient middle cerebral artery occlusion followed by reperfusion for 24 hours. The infarction and apoptosis were estimated by TTC staining and fluorescence TUNEL staining, respectively. Results-Overexpression of PAF-AH II was found in brains of transgenic mice by Western blot and enzymatic activity analyses. In immunohistochemistry, human PAF-AH II expression was found throughout the central nervous system, especially in neurons of neocortex, hippocampus, and basal ganglia. The neurological deficit scores, cerebral edema index, and relative infarction volume were all significantly (PϽ0.05) lower in transgenic mice (1.30Ϯ0.72, 1.12Ϯ0.04, and 14.0Ϯ7.7%, respectively) than in wild-type mice (2.56Ϯ0.93, 1.23Ϯ0.12, and 31.9Ϯ9.7%, respectively). Percentages of apoptotic cells were also significantly (PϽ0.001) lower in transgenic mice (cortex, 5.2Ϯ3.3%; hippocampus, 3.4Ϯ7.0%) than in wild-type mice (cortex, 41.1Ϯ16.9%; hippocampus, 58.9Ϯ15.3%). Conclusions-These results indicate that PAF-AH II exerts strong neuroprotective effects against ischemic injury and suggest a possibility for clinical use of this enzyme in cerebral ischemia.

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Section: Discussionmentioning

confidence: 75%

Neuroprotective Role of Transgenic PAF-Acetylhydrolase II in Mouse Models of Focal Cerebral Ischemia

Umemura

Kato

Hirashima

et al. 2007

Stroke

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“…Many of these actions have been studied in nonneural cells and are assumed to occur in the nervous system as well. Therefore, excessive PAF promotes neuronal damage, and PAFreceptor antagonists elicit neuroprotection in various models of neural injury (120,(133)(134)(135)(136)(137).…”

Section: Paf-mediated Cell Signal Transduction In the Nervous Systemmentioning

confidence: 99%

Synaptic lipid signaling

Bazán

2003

Journal of Lipid Research

231

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Neuronal cellular and intracellular membranes are rich in specialized phospholipids that are reservoirs of lipid messengers released by specific phospholipases and stimulated by neurotransmitters, neurotrophic factors, cytokines, membrane depolarization, ion channel activation, etc. Secretory phospholipases A 2 may be both intercellular messengers and generators of lipid messengers. The highly networked nervous system includes cells (e.g., astrocytes, oligodendrocytes, microglial cells, endothelial microvascular cells) that extensively interact with neurons; several lipid messengers participate in these interactions. This review highlights modulation of postsynaptic membrane excitability and long-term synaptic plasticity by cyclooxygenase-2-generated prostaglandin E2, arachidonoyldiacylcylglycerol, and arachidonic acid-containing endocannabinoids. The peroxidation of docosahexaenoic acid (DHA), a critical component of excitable membranes in brain and retina, is promoted by oxidative stress. DHA is also the precursor of enzyme-derived, neuroprotective docosanoids. The phospholipid platelet-activating factor is a retrograde messenger of long-term potentiation, a modulator of glutamate release, and an upregulator of memory formation. Lipid messengers modulate signaling cascades and contribute to cellular differentiation, function, protection, and repair in the nervous system. Lipidomic neurobiology will advance our knowledge of the brain, spinal cord, retina, and peripheral nerve function and diseases that affect them, and new discoveries on networks of signaling in health and disease will likely lead to novel therapeutic interventions. -Bazan, N. G. Synaptic lipid signaling: significance of polyunsaturated fatty acids and platelet-activating factor. J. Lipid Res.

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“…Produced by neurons in response to NMDA receptor activation (26), PAF increases glutamate release from presynaptic terminals (27) and can participate in long-term potentiation (LTP) of synaptic transmission (28,29) as well as learning and memory (30,31). PAF brain concentrations are dramatically increased in HAD (32) and other insults (33,34) and are associated with neurotoxicity. PAF has been shown to mediate NMDA excitotoxicity (35), and high concentrations can kill neurons in an NMDA receptor-dependent manner (32,36).…”

Section: Introductionmentioning

confidence: 99%

Synaptic activity becomes excitotoxic in neurons exposed to elevated levels of platelet-activating factor

Bellizzi¹

2005

Journal of Clinical Investigation

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Neurologic impairment in HIV-1-associated dementia (HAD) and other neuroinflammatory diseases correlates with injury to dendrites and synapses, but how such injury occurs is not known. We hypothesized that neuroinflammation makes dendrites susceptible to excitotoxic injury following synaptic activity. We report that platelet-activating factor, an inflammatory phospholipid that mediates synaptic plasticity and neurotoxicity and is dramatically elevated in the brain during HAD, promotes dendrite injury following elevated synaptic activity and can replicate HIV-1-associated dendritic pathology. In hippocampal slices exposed to a stable platelet-activating factor analogue, tetanic stimulation that normally induces long-term synaptic potentiation instead promoted development of calcium-and caspase-dependent dendritic beading. Chemical preconditioning with diazoxide, a mitochondrial ATP-sensitive potassium channel agonist, prevented dendritic beading and restored long-term potentiation. In contrast to models invoking excessive glutamate release, these results suggest that physiologic synaptic activity may trigger excitotoxic dendritic injury during chronic neuroinflammation. Furthermore, preconditioning may represent a novel therapeutic strategy for preventing excitotoxic injury while preserving physiologic plasticity.

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Evidence for platelet-activating factor as a novel mediator in experimental stroke in rabbits.

Cited by 100 publications

References 37 publications

Neuroprotective Role of Transgenic PAF-Acetylhydrolase II in Mouse Models of Focal Cerebral Ischemia

Neuroprotective Role of Transgenic PAF-Acetylhydrolase II in Mouse Models of Focal Cerebral Ischemia

Synaptic lipid signaling

Synaptic activity becomes excitotoxic in neurons exposed to elevated levels of platelet-activating factor

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