Ischemia‐Induced Alterations in Lipid Metabolism of the Gerbil Cerebral Cortex: I. Changes in Free Fatty Acid Liberation

Abstract

Does the impaired lipid metabolism during non-lethal transient ischemia truly recover within a few hours after recirculation? In an attempt to answer this question, we first investigated the time course of the changes in the amount and composition of free fatty acids (FFAs) accumulated during 5-min ischemia and after various postischemic recirculation durations (3 min, 1 h, 24 h, 3 days, and 6 days) in the gerbil cerebral cortex. Then those of FFAs liberated in response to the second 5-min ischemia at various recirculation intervals (3 min, 1 h, 3 days, and 6 days) following the initial one were also measured to evaluate the changes in the cellular response. The former study disclosed that the FFA levels transiently returned to the control levels at 1-h recirculation, increased again a few days after the onset of recirculation, followed by the final return to the control levels after 6-day recirculation. The latter study disclosed that the cellular response to the second ischemia was quite different from that to the initial one even after 6-day recirculation, suggesting that membrane lipid metabolism had not yet been recovered even at such a late period. We discuss the significance of the alterations in lipid metabolism.

Induced Tolerance to Ischemia in Gerbil Hippocampal Neurons

“…This change may, in all likelihood, contribute to the induced tolerance to subsequent ischemia that otherwise kills most of the neurons in the hippocampal CAl sector. Nakano et al (1990) have shown that biochemical change in lipid metab olism following brief ischemia continues for a long time. It took 6 days to return to the control levels following an ischemic insult.…”

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

“…Thus, a 5-mm infusion of tracer in our experiments gives ample time for the acyl-C0A pool to reach steady state in ischemia-reperfusion, where a slow (>1-h) recovery to control levels of fatty acids has been demonstrated (Rehncrona et al, 1982;Nakano et al, 1990). The values for~in Table 3 for PAM (0.026 ± 0.004) and for AA (0.0101 ± 0.0014) FATTY ACID METABOLISM IN ISCHEMIA 333 in control gerbil brain agree with previous estimates in rat brain (Washizaki et al, 1994;Grange et al, 1995) and emphasize the rapid turnover of unlabeled fatty acids in brain membrane phospholipids of control animals.…”

“…Furthermore, for both [ 3HIPAM and [3HI AA, a steady state is established within only a few minutes between plasma radioactivity and radioactivity in both the brain free fatty acid and acyl-CoA pools (Washizaki et al, 1994). As this time is much shorter than the time for recovery of normal unlabeled brain concentrations during reperfusion (Rehncrona et al, 1982;Nakano et al, 1990), it is very likely that tracer kinetics following ischemia rapidly reach a steady state for calculating values for X, the steady-state ratio of brain precursor poo1 specific activity to plasma specific activity.…”

“…c 21 is the plasma concentration of unlabeled unesterified fatty acid, in nmol/g, and c~is the plasma concentration of tracer, in dpmlg; Brain concentrations of unesterified fatty acids and acylCoA reach a maximum during ischemia and fall slowly to control levels within 1-2 h (Rehncrona et al, 1982;Nakano et al, 1990;Deutsch eta!., 1996;Rabin et al, 1997;authors' unpublished data). There is no reason to assume that the flux of unesterified radiolabeled fatty acid from plasma into brain across the blood-brain barrier is not the same in postperfusion and control animals, as this flux is independent of cerebral blood flow and is determined by the rate ofdissocia-328 0.…”

A possible role for sPLA2 in oligodendrocyte death and spinal cord injury.

“…Posttraumatic ischemia may result in energy failure that initiates a complex series of metabolic events, ultimately causing neuronal death. One such critical metabolic event is the activation of PLA 2 which can result in hydrolysis of membrane phospholipids, release of free fatty acids, generation of oxygen free radicals, and formation of eicosanoids (Nakano et al, 1990, Phillis and O'Regan, 2004, Muralikrishna Adibhatla and Hatcher, 2006.…”