Induction of secretory phospholipase A₂ in reactive astrocytes in response to transient focal cerebral ischemia in the rat brain

Abstract

Although mRNA expression of group IIA secretory phospholipase A 2 (sPLA 2 -IIA) has been implicated in responses to injury in the CNS, information on protein expression remains unclear. In this study, we investigated temporal and spatial expression of sPLA 2 -IIA mRNA and immunoreactivity in transient focal cerebral ischemia induced in rats by occlusion of the middle cerebral artery. Northern blot analysis showed a biphasic increase in sPLA 2 -IIA mRNA expression following 60-min of ischemia-reperfusion: an early phase at 30 min and a second increase at a late phase ranging from 12 h to 14 days. In situ hybridization localized the early-phase increase in sPLA 2 -IIA mRNA to the affected ischemic cortex and the late-phase increase to the penumbral area. Besides sPLA 2 -IIA mRNA, glial fibrillary acidic protein (GFAP) and cyclo-oxygenase-2 mRNAs, but not cytosolic PLA 2 , also showed an increase in the penumbral area at 3 days after ischemia-reperfusion. Immunohistochemistry of sPLA 2 -IIA indicated positive cells in the penumbral area similar to the GFAP-positive astrocytes but different from the isolectin B4-positive microglial cells. Confocal microscopy further confirmed immunoreactivity of sPLA 2 -IIA in reactive astrocytes but not in microglial cells. Taken together, these results demonstrate for the first time an up-regulation of the inflammatory sPLA 2 -IIA in reactive astrocytes in response to cerebral ischemia-reperfusion.

Omega-3 Fatty Acid Ethyl-Eicosapentaenoate Attenuates IL-1β-Induced Changes in Dopamine and Metabolites in the Shell of the Nucleus Accumbens: Involved with PLA2 Activity and Corticosterone Secretion

“…AA can also modulate neurotransmitter release, activate the HPA axis and change behavior (Smith et al, 1994;Narumiya et al, 1999). sPLA2 has been shown to participate in the PGE2 production (Kuwata et al, 1998) and involved in cerebral ischemia and neuroinflammation (Lin et al, 2004;Rosenberger et al, 2004). LPS and inflammatory cytokines can trigger the activity and expression of these PLA2 enzymes (Morioka et al, 2002;Rosenberger et al, 2004).…”

Integration of cytokine biology and lipid metabolism in stroke

“…These studies demonstrate that cPLA 2 is up-regulated after stroke and expression is largely confined to astrocytes. However, other studies did not observe any obvious change in the cPLA 2 mRNA expression in the penumbral area of the ischemic cortex at 3 days after tMCAO (129), which may be due to the selection of time points. To assess the role of cPLA 2 in stroke, transgenic 129/Sv mice (derived from C57BL/6) deficient in cPLA 2 were developed.…”

Inhibitors of Brain Phospholipase A2Activity: Their Neuropharmacological Effects and Therapeutic Importance for the Treatment of Neurologic Disorders

“…This process plays a central role in presynaptic neurotransmission (Moskowitz et al, 1983;Matsuzawa et al, 1996;Wei et al, 2003). In brain, Data summarized from Hirashima et al (1992); Matsuzawa et al (1996); Yang et al (1999);and Farooqui et al (2000b EFFECTS OF PLA 2 INHIBITORS 593 astrocytes express sPLA 2 , which can be induced in response to proinflammatory cytokines such as tumor necrosis factor-␣ and interleukin-1␤ (Lin et al, 2004). Mitochondrial fractions from rat brain, PC12, and U251 astrocytoma cell cultures contain significant sPLA 2 and iPLA 2 activities (Macchioni et al, 2004).…”