Influence of Platelet-Activating Factor on Cerebral Microcirculation in Rats

Uhl, Eberhard; Pickelmann, Sven; Röhrich, F.; Baethmann, A.; Schürer, L.; Faraci, Frank M.

doi:10.1161/01.str.30.4.880

Cited by 20 publications

(16 citation statements)

References 33 publications

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“…As an initial attempt to understand what role PAF might play in modulation of corticostriatal synapses, we chose low and high doses of cPAF that we believed would result in synaptic potentiation and failure of activity-dependent synaptic transmission, respectively, based on our in vitro studies of PAF-mediated effects on neuronal apoptosis, neuronal migration, and synaptic architecture and neurotransmission (Perry et al 1998;Tong et al 2001;Bellizzi et al 2005), and published data on PAF-mediated intracarotid effects on leukocyte-trafficking in an in vivo model of the blood-brain barrier (Uhl et al 1999). Thus, in our model system of cerebellar granule neuronal cultures (Tong et al 2001), a 130-nM dose of cPAF had no effect on neuronal apoptosis, and a 1,300-nM dose acutely induced loss of normal synaptic architecture and neurotransmission (Bellizzi et al 2005) and later induced neuronal apoptosis.…”

Section: Discussionmentioning

confidence: 99%

“…Thus, in our model system of cerebellar granule neuronal cultures (Tong et al 2001), a 130-nM dose of cPAF had no effect on neuronal apoptosis, and a 1,300-nM dose acutely induced loss of normal synaptic architecture and neurotransmission (Bellizzi et al 2005) and later induced neuronal apoptosis. Additionally, doses ≥1 μM of PAF induced arterial hypotension and increased leukocyte adhesion to cerebral microvessels (Uhl et al 1999), conditions that might predispose toward adverse outcomes in brain parenchyma supported by this microcirculation. We reasoned that these two concentrations of cPAF might approximate a physiologic and pathophysiologic level of PAF in our model system.…”

Section: Discussionmentioning

confidence: 99%

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The Phospholipid Mediator Platelet-Activating Factor Mediates Striatal Synaptic Facilitation

Tong

Gelbard

2007

Jrnl Neuroimmune Pharm

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The phospholipid mediator platelet-activating factor (PAF), an endogenous modulator of glutamatergic neurotransmission, can also be secreted by brain mononuclear phagocytes during HIV-1 infection. Platelet-activating factor can induce neuronal apoptosis by NMDA receptor-dependent and independent mechanisms. We now demonstrate that acute administration of sublethal doses of PAF to striatal slices augments synaptic facilitation in striatal neurons following high-frequency stimulation, which can be blocked by PAF receptor antagonists, suggesting that striatal synaptic facilitation can be augmented by PAF receptor agonism. We also demonstrate that repeated sublethal doses of PAF during tetanic stimulation can greatly increase the magnitude of postsynaptic potentials and action potentials, but a lethal dose of PAF destroys the capacity of corticostriatal synapses to achieve this augmented synaptic facilitation. Thus, the relative concentration and temporal pattern of PAF expression at glutamatergic synapses may govern whether it acts in a physiologic or pathophysiologic manner during striatal neurotransmission.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

The Phospholipid Mediator Platelet-Activating Factor Mediates Striatal Synaptic Facilitation

Tong

Gelbard

2007

Jrnl Neuroimmune Pharm

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“…Most studies suggested that PLA2 plays a potentially deleterious role in TBI by producing of inflammatory mediators and other second messengers (Stephenson et al, 1999;Sapirstein and Bonventre, 2000). PLA2 can hydrolyze membrane phospholipids and liberate free fatty acids including arachidonic acid, diacylglycerol (DAG), and precursor platelet activating factor (PAF), all of which are important components in immune and inflammatory responses (Dhillon et al, 1995;Bazan, 1998;Uhl et al, 1999).…”

Section: Inflammation-associated Genesmentioning

confidence: 99%

Altered expression of randomly selected genes in mouse hippocampus after traumatic brain injury

Long

Zou

et al. 2002

J of Neuroscience Research

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Using a cDNA microarray method, we analyzed gene expression profiles in mouse hippocampus after traumatic brain injury (TBI). Of 6,400 randomly selected arrayed genes and expressed sequence tags from a mouse cDNA library, 253 were found to be differentially expressed (106 increased and 147 decreased). Genes involved in cell homeostasis and calcium signaling were primarily up-regulated while those encoding mitochondrial enzymes, metabolic molecules, and structural proteins were predominantly down-regulated. Equal numbers of genes related to inflammatory reactions showed increased or decreased expression. Importantly, a large proportion of the dysregulated genes we identified have not been reported as differentially expressed in TBI models. Semiquantitative reverse-transcriptase polymerase chain reaction (RT-PCR) analyses of representative genes confirmed the validity of the corresponding microarray findings. Thus, our microarray-based evaluation of gene expression in traumatically injured hippocampus identified both known and novel genes that respond to TBI. Further investigation of these candidate molecules may suggest new ways to attenuate the traumatic effects of brain injury.

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“…Observation of the CNS microcirculation by intravital fluorescence microscopy is hampered by the protected localization of the brain and spinal cord within the skull and the spinal column, respectively. To gain intravital microscopic access to the CNS microcirculation, acute and chronic cranial window techniques have been developed for rodents, which allow observation of the pial and cortical (i.e., CNS grey matter) microcirculation, respectively (11,12). In EAE, however, inflammation is located in the CNS white matter with preference of the spinal cord.…”

Section: Introductionmentioning

confidence: 99%

α4-integrin-VCAM-1 binding mediates G protein–independent capture of encephalitogenic T cell blasts to CNS white matter microvessels

Vajkoczy¹,

Laschinger²,

Engelhardt³

2001

J. Clin. Invest.

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IntroductionThe CNS is considered an immunoprivileged site where the endothelial blood-brain barrier (BBB) tightly controls lymphocyte entry into the CNS. Under physiological conditions lymphocyte traffic into the CNS is low, whereas during inflammatory diseases of the CNS, such as multiple sclerosis (MS) or in the animal model experimental autoimmune encephalomyelitis (EAE), a large number of circulating lymphocytes readily gain access to the CNS. EAE is a CD4 + T cell-mediated autoimmune disease of the CNS, which is initiated by autoaggressive T cells activated outside the CNS. These encephalitogenic T cell blasts enter the CNS parenchyma across the healthy BBB and start the molecular events leading to inflammation, edema, and demyelination. Thus, the interaction of encephalitogenic T cells with the healthy BBB endothelium is a critical initial step in the pathogenesis of EAE.In general, lymphocyte recruitment across the vascular wall is regulated by the sequential interaction of different adhesion or signaling molecules on lymphocytes and endothelial cells lining the vessel wall (1). An initial transient contact of the circulating leukocyte with the vascular endothelium, generally mediated by adhesion molecules of the selectin family and their respective carbohydrate ligands, slows down the leukocyte in the bloodstream. Subsequently, the leukocyte rolls along the vascular wall with greatly reduced velocity. The rolling leukocyte can receive endothelial signals resulting in its firm adhesion to the endothelial surface. These signals are transduced by chemokines via G protein-coupled receptors on the leukocyte surface. Binding of a chemokine to its receptor results in a pertussis toxin-sensitive activation of integrins on the leukocyte surface. Only activated integrins mediate the firm adhesion of the leukocytes to the vascular endothelium by binding to their endothelial ligands, which belong to the Ig superfamily. This ultimately leads to the extravasation of the leukocyte. Successful recruitment of circulating leukocytes into the tissue depends on the productive leukocyte/endothelial interaction during each of these sequential steps.The adhesion molecules mediating the initial contact of T lymphocytes with the BBB endothelium are not yet defined. Selectins are not involved in T cell interaction with the BBB. Encephalitogenic T cell blasts lack expression of L-selectin (2), and E-and Pselectin are neither expressed at the BBB (3) nor functionally involved in the recruitment of autoaggressive T lymphocytes across the BBB during EAE (4). In contrast, constitutive expression of VCAM-1 in the CNS microvasculature of healthy SJL/N mice has been observed (5), and upregulation of ICAM-1 and VCAM-1 was reported on cerebral vessels during EAE preceding the perivascular infiltration by lymphocytes and the onset of disease (6). Direct in vivo evidence is still lacking for α4-integrin-mediated T cell interaction with VCAM-1 on blood-brain barrier-endothelium in experimental autoimmune encephalomyelitis (EAE). To investiga...

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Influence of Platelet-Activating Factor on Cerebral Microcirculation in Rats

Cited by 20 publications

References 33 publications

The Phospholipid Mediator Platelet-Activating Factor Mediates Striatal Synaptic Facilitation

The Phospholipid Mediator Platelet-Activating Factor Mediates Striatal Synaptic Facilitation

Altered expression of randomly selected genes in mouse hippocampus after traumatic brain injury

α4-integrin-VCAM-1 binding mediates G protein–independent capture of encephalitogenic T cell blasts to CNS white matter microvessels

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