Selective Acceleration of Arachidonic Acid Reincorporation into Brain Membrane Phospholipid Following Transient Ischemia in Awake Gerbil

Abstract

Awake gerbils were subjected to 5 mm of forebrain ischemia by clamping the carotid arteries for 5 mm and then allowing recirculation. Radiolabeled arachidonic or palmitic acid was infused intravenously for 5 mm at the start of recirculation, after which the brains were prepared for quantitative autoradiography or chemical analysis. Dilution of specific activity of the acyl-C0A pool was independently determined for these fatty acids in control gerbils and following 5 mm of ischemia and 5 mm of reperfusion. Using a quantitative method for measuring regional in vivo fatty acid incorporation into and turnover within brain phospholipids and determining unlabeled concentrations of acyl-CoAs following recirculation, it was shown that reperfusion after 5 mm of ischemia was accompanied by a threefold increase compared with the control in the rate of reincorporation of unlabeled arachidonate that had been released during ischemia, whereas reincorporation of released palmitate was not different from the control. Selective and accelerated reincorporation of arachidonate into brain phospholipids shortly after ischemia may ameliorate specific deleterious effects of arachidonate and its metabolites on brain membranes. Key Words: lschemia-Fatty acid metabolism-Phospholipid metabolism-Acyl-C0A-Brain-Gerbil-.Reperfusion-Recovery-Arachidonic acid-Palmitic acid.

Brain lipid metabolism in the cPLA2 knockout mouse

“…The apparent increase in the rate of incorporation and turnover of AA in PtdIns and increased turnover of ChoGpl, suggest that there are compensatory changes in other phospholipid-metabolizing enzymes. However, the reported resistance of the knockout mouse to middle cerebral artery occlusion (17,18) may arise from reduced availability and release of esterified AA during insult as a result of the absence of cPLA 2 activity (61)(62)(63). This interpretation is consistent with evidence that chronically administered LiCl in rats increases their resistance to cerebral ischemia (64), while decreasing brain cPLA 2 expression and AA turnover (21,54).…”

Brain metabolism of nutritionally essential polyunsaturated fatty acids depends on both the diet and the liver

“…Excess AA metabolism can contribute to neuronal damage in experimental ischemia, glutamate excitotoxicity, neuroinflammation, and cerebral trauma 45,[60][61][62][63][64] . This, among other factors, may explain why an n-3 PUFA dietary deficiency might increase brain vulnerability to these insults.…”

Linoleic acid participates in the response to ischemic brain injury through oxidized metabolites that regulate neurotransmission

“…The majority of unesterified AA and DHA are re-esterified into the phospholipid membrane 44 , whereas a small portion (~3%) is converted via non-enzymatic or enzymatic pathways into oxylipins 41, 45–47 that regulate the brain’s response to injury 2–4 . This response involves oxylipins that acutely down-regulate neuronal hyperexcitability 48 and enhance vasodilation 49 as a protective mechanism.…”