Brain Protection after Anoxic Brain Injury: Is Lactate Supplementation Helpful?

Abstract

While sudden loss of perfusion is responsible for ischemia, failure to supply the required amount of oxygen to the tissues is defined as hypoxia. Among several pathological conditions that can impair brain perfusion and oxygenation, cardiocirculatory arrest is characterized by a complete loss of perfusion to the brain, determining a whole brain ischemic-anoxic injury. Differently from other threatening situations of reduced cerebral perfusion, i.e., caused by increased intracranial pressure or circulatory shock, resuscitated patients after a cardiac arrest experience a sudden restoration of cerebral blood flow and are exposed to a massive reperfusion injury, which could significantly alter cellular metabolism. Current evidence suggests that cell populations in the central nervous system might use alternative metabolic pathways to glucose and that neurons may rely on a lactate-centered metabolism. Indeed, lactate does not require adenosine triphosphate (ATP) to be oxidated and it could therefore serve as an alternative substrate in condition of depleted energy reserves, i.e., reperfusion injury, even in presence of adequate tissue oxygen delivery. Lactate enriched solutions were studied in recent years in healthy subjects, acute heart failure, and severe traumatic brain injured patients, showing possible benefits that extend beyond the role as alternative energetic substrates. In this manuscript, we addressed some key aspects of the cellular metabolic derangements occurring after cerebral ischemia-reperfusion injury and examined the possible rationale for the administration of lactate enriched solutions in resuscitated patients after cardiac arrest.

Lactate receptor HCAR1 regulates neurogenesis and microglia activation after neonatal hypoxia-ischemia

“…In human HI, reperfusion often occurs, which can lead to reperfusion injury. Although lactate administrations has been shown to reduce reperfusion injury in adult mice and humans ( Annoni et al, 2021 ), a recent study from adult rats suggested that the effect was HCAR1 independent ( Buscemi et al, 2021 ). We are not aware of any studies on the effect of lactate and HCAR1 on reperfusion injury in neonatal HI.…”

Metabolic and Cellular Compartments of Acetyl-CoA in the Healthy and Diseased Brain

“…Such a thesis is supported by the results of clinical trials that revealed beneficial effects of infusion hyperosmic sodium lactate, being a direct acetyl-CoA precursor. It bypasses glycolysis as the ATP consuming pathway and alleviates reperfusion injury in patients after focal cerebral ischemia [ 46 ]. The positive influences of hypertonic lactate infusion in brains of TBI patients or those with acute cardiac failure may be extended beyond its role as an alternative energy precursor, as it is also an anti-oedematous agent, scavenger of free radicals, Zn/Ca chelator and suppressor of reperfusion-evoked glutamate/Zn/NO excitotoxicity [ 46 , 47 ].…”

“…It bypasses glycolysis as the ATP consuming pathway and alleviates reperfusion injury in patients after focal cerebral ischemia [ 46 ]. The positive influences of hypertonic lactate infusion in brains of TBI patients or those with acute cardiac failure may be extended beyond its role as an alternative energy precursor, as it is also an anti-oedematous agent, scavenger of free radicals, Zn/Ca chelator and suppressor of reperfusion-evoked glutamate/Zn/NO excitotoxicity [ 46 , 47 ]. For obvious reasons, the effects of lactate/HB on the acetyl-CoA status in injured brains were not investigated in humans.…”

“…Cardiac arrest in mice lasting 8 min followed by cardiopulmonary resuscitation resulted in a rapid and deepening-with-time decrease in thiamine diphosphate (TDP) and ATP levels in the brain cortex, resulting in a high rate of animal mortality. This was due to phosphorylation-induced inhibition of PDHC activity, yielding a deficit of acetyl-CoA in neurons [ 46 , 52 ]. Daily i.v.…”

Curcumin-Impregnated Drug Delivery Systems May Show Promise in the Treatment of Diseases Secondary to Traumatic Brain Injury: Systematic Review

“…[6][7][8][9] Brain ischemia often occurs after TBI and deaths are common. 10,11 Cerebrovascular autoregulation and CO 2 reactivity, which are vital mechanisms that provide cerebral blood flow, are partially or completely impaired following TBI. 12 Chronic depolarization of vascular smooth muscle cells and cerebral vasospasm resulting in TBI are also seen in most cases.…”