Eicosanoid Production in the Caudate Nucleus and Dorsal Hippocampus after Forebrain Ischemia: A Microdialysis Study

Abstract

Summary: Thromboxane (Tx)B2 and 6-keto-prosta glandin (6-keto-PG) Flo< formation in the hippocampus and caudate nucleus were evaluated by microdialysis dur ing and following forebrain ischemia. Spontaneously hy pertensive rats were subjected to bilateral carotid artery occlusion with simultaneous hypotension for 8, 14, or 20 min. Dialysate was collected during the ischemic interval and during the reperfusion period. TxB2 and 6-keto PGFlo< levels were measured by radioimmunoassay. In both structures, TxBz production increased significantly during the reperfusion period in all three ischemic groups. By contrast, increased 6-keto-PGF 10< elaboration was ob served after only the longest ischemic duration. While TxB2 levels gradually decreased during the 3-h reperfu sion period in all groups, the levels in the group subjected to 8 min of ischemia returned to control values most rap idly. A relationship between the duration of ischemia andThe liberation of arachidonic acid during cerebral ischemia (Bazan, 1970; Gardiner et aI., 1981; Rehn crona et aI., 1982; Goto et aI., 1988; Yoshida et aI., 1986) and its subsequent metabolism by the cyclo oxygenase and lipoxygenase enzyme systems to yield eicosanoids have been demonstrated by sev eral investigators. The effect of eicosanoids on isch emic neuronal injury has been the subject of exten-

N‐methyl‐D‐aspartate‐evoked release of cyclo‐oxygenase products in rabbit hippocampus: An in vivo microdialysis study

“…The basal levels of both eicosanoids in the dialysis medium of the rabbit hippocampus observed in this study agree with data for the rat hippocampus presented by Patel et al (1992). We did not measure the relative recovery of eicosanoids, either in vitro or in vivo.…”

“…ucts TX B, and 6-keto PGF,, have been detected in brain after ischemia (Gaudet et al, 1980; Shohami et al, 1982; Black et al, 1984; Dempsey et al, 1986;Dorman, 1988; Patel et al, 1992). A documented pathological role of excitatory amino acid receptors in brain ischemia (Benveniste et al, 1984;Choi, 1988; Siesjo, 1992) may suggest the relation between the activation of glutamatergic receptors and the formation of TX B, and 6-keto PGF,, in brain.…”

“…We did not measure the relative recovery of eicosanoids, either in vitro or in vivo. However, considering a 6-7% in vitro recovery found by Patel et al (1992) for their commercial 2 mm CMA-10 probes perfused at the rate of 2 pl/min, one can expect a slightly higher recovery for our 10-mm cuprophan probes perfused at a rate of 2.5 pl/min.…”

“…Different prostanoids, products of arachidonate metabolism via the cyclo-oxygenase pathway, are less hydrophobic, and their release from neurons to the extracellular fluid in the brain may be followed by microdialysis combined with HPLC or radioimmunoassay detection (Yergey and Heyes, 1990; Patel et al, 1992). In vivo microdialysis mainly used in studies on catecholamine and amino acid neurotransmitters (for review, see Benveniste, 1989; Ungerstedt, 1991), has also been utilised in our laboratory in studies on calcium fluxes (Lazarewicz et al, 1986, 1992; Lazarewicz and Salinska, 1993).…”

Arachidonic acid metabolites in CSF in hypoxic‐ischaemic encephalopathy of newborn infants

“…On reperfusion, when oxygen is available, arachidonic acid metabolism can occur, resulting in eicosanoid formation, as well as in generation of activated oxygen species (10). Changes of eicosanoid levels in brain cortex have been described after modifications of oxygen supply in experimental animal models (7,(9)(10)(11)(12)(13). It seems that maximal changes of eicosanoid levels occur during recovery more than during hypoxia-ischaemia and therefore may play a role in the neuronal death subsequent to hypoxia-ischaemia, spinal cord injury, and other neurodegenerative diseases (14).…”