Online citations, reference lists, and bibliographies.
← Back to Search

Neuroprotective Effects Of A Nanocrystal Formulation Of SPLA2 Inhibitor PX-18 In Cerebral Ischemia/reperfusion In Gerbils

Q. Wang, A. Sun, J. Pardeike, R. Mueller, G. Sun
Published 2009 · Biology, Medicine

Cite This
Download PDF
Analyze on Scholarcy
Share
The group IIA secretory phospholipase A2 (sPLA(2)-IIA) has been studied extensively because of its involvement in inflammatory processes. Up-regulation of this enzyme has been shown in a number of neurodegenerative diseases including cerebral ischemia and Alzheimer's disease. PX-18 is a selective sPLA(2) inhibitor effective in reducing tissue damage resulting from myocardial infarction. However, its use as a neuroprotective agent has been hampered due to its low solubility. In this study, we test the possible neuroprotective effects of PX-18 formulated as a suspension of nanocrystals. Transient global cerebral ischemia was induced in gerbils by occlusion of both common carotid arteries for 5 min. Four days after ischemia/reperfusion (I/R), extensive delayed neuronal death, DNA damage, and increases in reactive astrocytes and microglial cells were observed in the hippocampal CA1 region. PX-18 nanocrystals (30 and 60 mg/kg body wt) and vehicle controls were injected i.p. immediately after I/R. PX-18 nanocrystal injection significantly reduced delayed neuronal death, DNA damage, as well as glial cell activation. These findings demonstrated the effective neuroprotection of PX-18 in the form of nanocrystal against I/R-induced neuronal damage. The results also suggest that nanocrystals hold promise as an effective strategy for the delivery of compounds with poor solubility that would otherwise be precluded from preclinical development.
This paper references
10.1016/J.PLEFA.2006.12.004
Prostaglandin production in human coronary artery endothelial cells is modulated differentially by selective phospholipase A(2) inhibitors.
P. Rastogi (2007)
10.1016/S1385-299X(99)00012-4
Neuronal apoptosis studied by a sequential TUNEL technique: a method for tract-tracing.
A. Hara (1999)
10.1016/J.IJPHARM.2006.02.045
Oral bioavailability of cyclosporine: solid lipid nanoparticles (SLN) versus drug nanocrystals.
R. Mueller (2006)
10.1016/0006-8993(94)90719-6
Expression of group II phospholipase A2 in rat brain after severe forebrain ischemia and in endotoxic shock
I. Lauritzen (1994)
10.2174/1381612053507521
Phospholipase A2 inhibitors as potential anti-inflammatory agents.
M. Meyer (2005)
10.1016/J.BIOMATERIALS.2006.01.038
Lectin-conjugated PEG-PLA nanoparticles: preparation and brain delivery after intranasal administration.
X. Gao (2006)
10.1016/J.IJPHARM.2005.03.027
Preparation and in vitro evaluation of chitosan nanoparticles containing a caspase inhibitor.
Y. Aktaş (2005)
10.1016/S0378-5173(00)00639-6
The role of plasma proteins in brain targeting: species dependent protein adsorption patterns on brain-specific lipid drug conjugate (LDC) nanoparticles.
A. Gessner (2001)
10.1021/BC050217O
Development and brain delivery of chitosan-PEG nanoparticles functionalized with the monoclonal antibody OX26.
Y. Aktaş (2005)
10.2174/187152906777441830
Inhibition of sPLA2-IIA, C-reactive protein or complement: new therapy for patients with acute myocardial infarction?
P. Krijnen (2006)
10.1194/JLR.R300016-JLR200
Phospholipase A2 in the central nervous system: implications for neurodegenerative diseases.
G. Sun (2004)
10.1016/S0006-8993(02)03543-6
Resveratrol protects against global cerebral ischemic injury in gerbils
Q. Wang (2002)
10.1166/JNN.2006.480
New method for the effective production of ultrafine drug nanocrystals.
J. Möschwitzer (2006)
10.1016/J.EJPB.2005.05.009
Drug nanocrystals of poorly soluble drugs produced by high pressure homogenisation.
C. Keck (2006)
10.1002/jnr.10131
Secreted phospholipase A2 potentiates glutamate‐induced calcium increase and cell death in primary neuronal cultures
M. DeCoster (2002)
10.1016/0005-2760(89)90013-1
Oligomers of prostaglandin B1 inhibit in vitro phospholipase A2 activity.
R. Franson (1989)
10.1016/j.neuropharm.2005.02.011
S-2474, a novel nonsteroidal anti-inflammatory drug, rescues cortical neurons from human group IIA secretory phospholipase A2-induced apoptosis
T. Yagami (2005)
10.1186/1742-2094-3-1
Serum antibodies from Parkinson's disease patients react with neuronal membrane proteins from a mouse dopaminergic cell line and affect its dopamine expression
V. C. Huber (2005)
10.1161/01.ATV.19.5.1291
Role of group II secretory phospholipase A2 in atherosclerosis: 2. Potential involvement of biologically active oxidized phospholipids.
N. Leitinger (1999)
10.1046/j.1471-4159.2003.01712.x
Human group IIA secretory phospholipase A2 potentiates Ca2+ influx through L‐type voltage‐sensitive Ca2+ channels in cultured rat cortical neurons
T. Yagami (2003)
10.1111/j.1471-4159.2004.02540.x
Induction of secretory phospholipase A2 in reactive astrocytes in response to transient focal cerebral ischemia in the rat brain
T. Lin (2004)
10.1016/S0378-5173(97)00311-6
Nanosuspensions for the formulation of poorly soluble drugs: I. Preparation by a size-reduction technique
R. Mueller (1998)
10.1016/j.cellbi.2007.03.005
Activation of cPLA2 and sPLA2 in astrocytes exposed to simulated ischemia in vitro
B. Gabryel (2007)
10.1016/J.BBALIP.2005.08.014
Diverse cellular localizations of secretory phospholipase A2 enzymes in several human tissues.
Seiko Masuda (2005)
10.1186/1742-2094-3-28
Secretory PLA2-IIA: a new inflammatory factor for Alzheimer's disease
Guna S D Moses (2006)
10.1016/S0304-3940(99)00709-0
Secretory phospholipase A2 potentiates glutamate-induced rat striatal neuronal cell death in vivo
M. Kolko (1999)
10.1002/jnr.10239
Glutamate signalling and secretory phospholipase A2 modulate the release of arachidonic acid from neuronal membranes
E. B. Rodriguez de Turco (2002)
10.1016/J.BMC.2004.01.022
Inhibition of the complete set of mammalian secreted phospholipases A(2) by indole analogues: a structure-guided study.
Brian P. Smart (2004)
10.1016/S0006-8993(96)01387-X
Fluoro-Jade: a novel fluorochrome for the sensitive and reliable histochemical localization of neuronal degeneration
L. Schmued (1997)
10.1007/978-1-4615-5325-0_49
PX-52, A novel inhibitor of 14 kDa secretory and 85 kDa cytosolic phospholipases A2.
R. Franson (1997)
10.1152/AJPHEART.00887.2002
Type II secretory phospholipase A2 binds to ischemic flip-flopped cardiomyocytes and subsequently induces cell death.
R. Nijmeijer (2003)
10.1016/J.FREERADBIOMED.2005.08.044
Phospholipase A2, reactive oxygen species, and lipid peroxidation in cerebral ischemia.
Rao Muralikrishna Adibhatla (2006)
10.1161/ATVBAHA.107.139352
Circulating Secretory Phospholipase A2 Activity and Risk of Incident Coronary Events in Healthy Men and Women: The EPIC-NORFOLK Study
Z. Mallat (2007)
10.1097/00001756-200210280-00026
Secretory phospholipase A2-mediated neuronal cell death involves glutamate ionotropic receptors
M. Kolko (2002)
10.1016/J.ATHEROSCLEROSIS.2006.08.062
Expression of secretory phospholipase A2s in human atherosclerosis development.
M. Kimura-Matsumoto (2008)
10.1016/j.jconrel.2008.10.013
Liposome encapsulated polyethylenimine/ODN polyplexes for brain targeting.
Y. Ko (2009)
10.1016/S0304-3940(98)00838-6
Genes encoding multiple forms of phospholipase A2 are expressed in rat brain
G. Y. Molloy (1998)
10.1021/jm800422v
Highly specific and broadly potent inhibitors of mammalian secreted phospholipases A2.
R. Oslund (2008)
10.1080/10611860500071292
Polysorbate-stabilized solid lipid nanoparticles as colloidal carriers for intravenous targeting of drugs to the brain: Comparison of plasma protein adsorption patterns
T. Göppert (2005)
10.1124/MOL.61.1.114
Human group IIA secretory phospholipase A2 induces neuronal cell death via apoptosis.
T. Yagami (2002)
10.1194/JLR.M400469-JLR200
Macrophage-specific expression of group IIA sPLA2 results in accelerated atherogenesis by increasing oxidative stress Published, JLR Papers in Press, May 16, 2005. DOI 10.1194/jlr.M400469-JLR200
U. J. Tietge (2005)
10.1016/j.brainres.2006.11.080
RETRACTED: Secretory phospholipase A2 IIA is up-regulated by TNF-α and IL-1α/β after transient focal cerebral ischemia in rat
R. M. Adibhatla (2007)
10.1021/JM060082N
Inhibition of secreted phospholipase A2. 4-glycerol derivatives of 4,5-dihydro-3-(4-tetradecyloxybenzyl)-1,2,4-4H-oxadiazol-5-one with broad activities.
M. Touaibia (2007)
10.1248/BPB.27.1158
Secretory phospholipase A2.
M. Murakami (2004)
10.1074/jbc.271.51.32722
Synergy by Secretory Phospholipase A2 and Glutamate on Inducing Cell Death and Sustained Arachidonic Acid Metabolic Changes in Primary Cortical Neuronal Cultures*
M. Kolko (1996)
10.1097/MPA.0b013e3185d9b9b
Role of Substance P and Bradykinin in Acute Pancreatitis Induced by Secretory Phospholipase A2
E. Camargo (2008)
10.1093/cvr/cvn234
Secreted phospholipase A2 type IIA as a mediator connecting innate and adaptive immunity: new role in atherosclerosis.
E. Ibeas (2009)
10.1166/JNN.2004.078
Drug delivery to the brain--realization by novel drug carriers.
R. Mueller (2004)
10.1016/J.JBIOTEC.2004.06.007
Challenges and solutions for the delivery of biotech drugs--a review of drug nanocrystal technology and lipid nanoparticles.
R. H. Muller (2004)
10.4049/jimmunol.168.4.1926
Inflammatory Response and Glutathione Peroxidase in a Model of Stroke1
N. Ishibashi (2002)
10.1021/BI048080X
An apolipoprotein E-derived peptide mediates uptake of sterically stabilized liposomes into brain capillary endothelial cells.
I. Sauer (2005)
10.1111/j.1365-2362.2008.01933.x
Secretory type II phospholipase A2 in culprit coronary lesions is associated with myocardial infarction
R. Nijmeijer (2008)



This paper is referenced by
10.3892/mmr.2014.3084
Changes in the expression of DNA-binding/differentiation protein inhibitors in neurons and glial cells of the gerbil hippocampus following transient global cerebral ischemia
J. Lee (2015)
10.1021/acschemneuro.5b00073
Synthetic and natural inhibitors of phospholipases A2: their importance for understanding and treatment of neurological disorders.
W. Ong (2015)
10.1016/j.jns.2014.06.016
Changes and expressions of Redd1 in neurons and glial cells in the gerbil hippocampus proper following transient global cerebral ischemia
C. H. Lee (2014)
10.1016/J.JDDST.2015.07.018
Nanomedicines and stroke: Toward translational research
Alice Gaudin (2015)
10.1186/s12929-015-0135-1
Hydrogen sulfide protects spinal cord and induces autophagy via miR-30c in a rat model of spinal cord ischemia-reperfusion injury
L. Li (2015)
10.1016/j.jep.2011.05.024
Neuroprotective effects of Eleutherococcus senticosus bark on transient global cerebral ischemia in rats.
D. Lee (2012)
10.1007/s12035-010-8108-6
Low Molecular Weight Phospholipases A2 in Mammalian Brain and Neural Cells: Roles in Functions and Dysfunctions
G. Goracci (2010)
10.1002/adhm.201700818
Cell‐Based Drug Delivery and Use of Nano‐and Microcarriers for Cell Functionalization
A. Timin (2018)
10.2217/nnm-2018-0163
Application of nanodiagnostics and nanotherapy to CNS diseases.
W. Zhang (2018)
10.2174/092986712798992138
Nanotechnology based diagnostic and therapeutic strategies for neuroscience with special emphasis on ischemic stroke.
S. B. Nair (2012)
10.1016/j.addr.2011.02.001
Physical and chemical stability of drug nanoparticles.
L. Wu (2011)
10.1016/j.lfs.2017.03.022
ACA, an inhibitor phospholipases A2 and transient receptor potential melastatin‐2 channels, attenuates okadaic acid induced neurodegeneration in rats
M. Çakır (2017)
10.1016/B978-0-12-407178-0.00006-5
Inflammatory pathways in spinal cord injury.
S. David (2012)
10.1021/acs.jnatprod.7b00515
Scalaradial Is a Potent Inhibitor of Transient Receptor Potential Melastatin 2 (TRPM2) Ion Channels.
J. Starkus (2017)
10.1016/j.etap.2012.07.011
Recent advances in benefits and hazards of engineered nanoparticles.
K. Radad (2012)
10.2174/13816128113199990403
Effects of nanosuspension formulations on transport, pharmacokinetics, in vivo targeting and efficacy for poorly water-soluble drugs.
Y. Wang (2014)
10.1016/j.ejpb.2011.01.007
State of the art of nanocrystals--special features, production, nanotoxicology aspects and intracellular delivery.
R. Mueller (2011)
Semantic Scholar Logo Some data provided by SemanticScholar