Ischemia‐Induced Changes in Cerebral Mitochondrial Free Fatty Acids, Phospholipids, and Respiration in the Rat

Abstract

Changes in the free fatty acid pool size and fatty acyl chain composition of mitochondrial membrane phospholipids and their relation to disruption of mitochondrial function were examined in rat brains after 30 min of cerebral ischemia (Pulsinelli‐Brierley model) and 60 min of normoxic reoxygenation. During ischemia, significant hydrolysis of polyunsaturated molecular species from diacyl phosphatidylcholine, particularly fatty acyl 20:4 (arachidonic acid; 20% decrease) and 22:6 (docosahexaenoic acid; 15% decrease), was observed. Thirty minutes of ischemia caused a 16% loss of 18:2 (linoleic acid) from phosphatidylethanolamine. Recirculation for 60 min did not return the polyunsaturated fatty acid content of phospholipids to normal. Total content of free fatty acids increased during ischemia, particularly 18:2 and 22:6, which exhibited the most dramatic rise. The free fatty acid pool size continued to increase during 60 min of recirculation. The respiratory control ratio decreased significantly during 30 min of ischemia with no apparent recovery following 60 min of reoxygenation. The degree of free radical‐mediated lipid peroxidation in mitochondria was significantly increased during ischemia and reperfusion. It was concluded that (a) 30 min of cerebral ischemia caused differential degradation in each of the phospholipid classes and preferential hydrolysis of the polyunsaturated molecular species and (b) 60 min of normoxic reperfusion failed to promote reacylation of the mitochondrial phospholipids and restoration of normal respiration.

Examination of Physiological Function and Biochemical Disorders in a Rat Model of Prolonged Asphyxia-Induced Cardiac Arrest followed by Cardio Pulmonary Bypass Resuscitation

“…As shown in Table 4, 2-isomers of lysophospholipids are increased as much as 1-isomers. Furthermore, the data do not support the concept of preferential hydrolysis of certain fatty acids, such as arachidonic acid or docosahexaenoic acid [35], [40]. These results strongly indicate that phospholipase A2 is not solely responsible for the accumulation of lysophospholipids.…”

“…Lysophospholipids are an intermediate of biosynthesis as well as hydrolysis of membrane phospholipid but, in the context of damage and ischemia, predominantly represent degradation [35]. A decrease in phospholipid content with a concomitant increase in lysophospholipids and free fatty acids is often found in pathological conditions including ischemia [36], [37].…”

Chronic daily administration of ethyl docosahexaenoate protects against gerbil brain ischemic damage through reduction of arachidonic acid liberation and accumulation

“…However, under conditions of ischemia, free AA production exceeds utilization, and accumulation ensues [29]. A rapid increase in free AA during ischemia is generally considered as due to impaired phospholipid reacylation secondary to energy failure/ATP depletion because the reacylation process is an energy-requiring process [30,31]. Simultaneously, ischemia-induced glutamate release contributes to increased free AA because glutamate receptor stimulation leads to phosphoinositide hydrolysis and PLA 2 activation, which results in further phospholipid degradation and free AA liberation and accumulation [30,32].…”

Characterization of mitochondrial bioenergetics in neonatal anoxic model of rats

“…This critical requirement is compromised during anoxic injury triggering cascade of biochemical events which lead to excitotoxicity and influx of Ca 2+ ions. This results in overproduction of nitric oxide (NO) apart from other reactive oxygen species (ROS) within the mitochondria (Magistretti and Allaman 2013;Sun and Gilboe 1994;Herrera-Marschitz et al 2014). These mitochondrial events lead to opening of membrane permeability transition pore and release of proapoptotic proteins like cytochrome c which ultimately cause mitochondrial dysfunction and cell death (Morin et al 2003).…”