Lactate Produced by Glycogenolysis in Astrocytes Regulates Memory Processing

When administered either systemically or centrally, glucose is a potent enhancer of memory processes. Measures of glucose levels in extracellular fluid in the rat hippocampus during memory tests reveal that these levels are dynamic, decreasing in response to memory tasks and loads; exogenous glucose blocks these decreases and enhances memory. The present experiments test the hypothesis that glucose enhancement of memory is mediated by glycogen storage and then metabolism to lactate in astrocytes, which provide lactate to neurons as an energy substrate. Sensitive bioprobes were used to measure brain glucose and lactate levels in 1-sec samples. Extracellular glucose decreased and lactate increased while rats performed a spatial working memory task. Intrahippocampal infusions of lactate enhanced memory in this task. In addition, pharmacological inhibition of astrocytic glycogenolysis impaired memory and this impairment was reversed by administration of lactate or glucose, both of which can provide lactate to neurons in the absence of glycogenolysis. Pharmacological block of the monocarboxylate transporter responsible for lactate uptake into neurons also impaired memory and this impairment was not reversed by either glucose or lactate. These findings support the view that astrocytes regulate memory formation by controlling the provision of lactate to support neuronal functions

Circulatory recovery is as fast with air ventilation as with 100% oxygen after asphyxia-induced cardiac arrest in piglets.

We investigated return of spontaneous circulation and of cerebral oxygenation after asphyxia-induced cardiac arrest, using ventilation with air, throughout, or with 100% oxygen for a shorter or longer period. Arterial pressure, heart rate, regional cerebral oxygen saturation (CrSO2) and brain tissue oxygen tension (PbtO2) were measured in one day old piglets that were hypoventilated with air and left in apnea until cardiac arrest. They were randomly assigned to be resuscitated with air (n=13), or with oxygen for 3 (n=12) or 30 min (n = 13) and then with air. Nine, 10, and 10 animals, respectively, needed closed chest cardiac massage. One, none, and 1, respectively, died. Median (quartile range) times from start of ventilation until heart rate reached 150 bpm were 67 (60-76), 88 (76-126), and 68 (56-81) s. They were not significantly different, nor were the arterial pressure responses, times until CrSO2 reached 30%, or times until PbtO2 had increased by 0.1 kPa from its nadir. Peak PbtO2 values during resuscitation were 4.2 (3.3-5.4), 12 (6.4 - 15), and 25 (15 - 36) kPa. Thus, pure oxygen did not accelerate the recovery of circulation or of cerebral oxygenation, while even a brief exposure caused cerebral hyperoxia

Associations between serum cortisol, cardiovascular function and neurological outcome following acute global hypoxia in the newborn piglet

Perinatal asphyxia is a significant contributor to neonatal brain injury. However, there is significant variability in neurological outcome in neonates after global hypoxiaischemia. The aims of this study were to identify which physiological response/s during global hypoxiaischemia influence the severity of brain injury and to assess their relative importance. Hypoxia/hypercapnia was induced in 20 anaesthetized piglets by reducing the inspired oxygen fraction to 10% and the ventilation rate from 30 to 10 breaths per minute for 45 min. Neurological outcome was assessed using functional markers including cerebral function amplitude (via electroencephalography) and cerebral impedance, and the structural marker microtubule associated protein-2 by immunohistochemistry at 6 h post hypoxia. Significant variability in neurological outcome was observed following the constant hypoxia/hypercapnia insult. There was a high degree of variability in cardiovascular function (mean arterial blood pressure and heart rate) and serum cortisol concentrations in response to hypoxia. More effective maintenance of cardiovascular function and higher serum cortisol concentrations were associated with a better outcome. These two variables were strongly associated with neurological outcome, and together explained 68% of the variation in the severity of neurological outcome. The variability in the cardiovascular and cortisol responses to hypoxia may be a more important determinant of neurological outcome then previously recognized