Skip to Content
MilliporeSigma
  • Neuroprotective effects of a nanocrystal formulation of sPLA(2) inhibitor PX-18 in cerebral ischemia/reperfusion in gerbils.

Neuroprotective effects of a nanocrystal formulation of sPLA(2) inhibitor PX-18 in cerebral ischemia/reperfusion in gerbils.

Brain research (2009-06-17)
Qun Wang, Albert Y Sun, Jana Pardeike, Rainer H Müller, Agnes Simonyi, Grace Y Sun
ABSTRACT

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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
ECO TWEEN® 80, viscous liquid
Sigma-Aldrich
TWEEN® 80, viscous liquid, Preservative Free, Low-peroxide; Low-carbonyls
Sigma-Aldrich
TWEEN® 80, BioXtra, viscous liquid
Sigma-Aldrich
TWEEN® 80, for molecular biology, syrup
Sigma-Aldrich
TWEEN® 80, suitable for cell culture, suitable for insect cell culture, viscous liquid
Sigma-Aldrich
TWEEN® 80, viscous liquid
Sigma-Aldrich
TWEEN® 80, from non-animal source
Sigma-Aldrich
TWEEN® 80, viscous liquid, Low-peroxide