Hepatic-portal vein infusions of glucagon-like peptide-1 reduce meal size and increase c-Fos expression in the nucleus tractus solitarii, area postrema and central nucleus of the amygdala in rats

We recently reported that brief, remotely controlled intrameal hepatic-portal vein infusions of glucagon-like peptide-1 (GLP-1) reduced spontaneous meal size in rats. To investigate the neurobehavioural correlates of this effect, we equipped male Sprague-Dawley rats with hepatic-portal vein catheters and assessed (i) the effect on eating of remotely triggered infusions of GLP-1 (1 nmol/kg, 5 min) or vehicle during the first nocturnal meal after 3 h of food deprivation and (ii) the effect of identical infusions performed at dark onset on c-Fos expression in several brain areas involved in the control of eating. GLP-1 reduced (P < 0.05) the size of the first nocturnal meal and increased its satiety ratio. Also, GLP-1 increased (P < 0.05) the number of c-Fos-expressing cells in the nucleus tractus solitarii, the area postrema and the central nucleus of the amygdala, but not in the arcuate or paraventricular hypothalamic nuclei. These data suggest that the nucleus tractus solitarii, the area postrema and the central nucleus of the amygdala play a role in the eating-inhibitory actions of GLP-1 infused into the hepatic-portal vein; it remains to be established whether activation of these brain nuclei reflect satiation, aversion, or both.

The effect of high-energy extracorporeal shock waves on hyaline cartilage of adult rats in vivo

The aim of this study was to determine if extracorporeal shock wave therapy (ESWT) in vivo affects the structural integrity of articular cartilage. A single bout of ESWT (1500 shock waves of 0.5 mJ/mm(2)) was applied to femoral heads of 18 adult Sprague-Dawley rats. Two sham-treated animals served as controls. Cartilage of each femoral head was harvested at 1, 4, or 10 weeks after ESWT (n = 6 per treatment group) and scored on safranin-O-stained sections. Expression of tenascin-C and chitinase 3-like protein 1 (Chi3L1) was analyzed by immunohistochemistry. Quantitative real-time polymerase chain reaction (PCR) was used to examine collagen (II)alpha(1) (COL2A1) expression and chondrocyte morphology was investigated by transmission electron microscopy no changes in Mankin scores were observed after ESWT. Positive immunostaining for tenascin-C and Chi3L1 was found up to 10 weeks after ESWT in experimental but not in control cartilage. COL2A1 mRNA was increased in samples 1 and 4 weeks after ESWT. Alterations found on the ultrastructural level showed expansion of the rough-surfaced endoplasmatic reticulum, detachment of the cell membrane and necrotic chondrocytes. Extracorporeal shock waves caused alterations of hyaline cartilage on a molecular and ultrastructural level that were distinctly different from control. Similar changes were described before in the very early phase of osteoarthritis (OA). High-energy ESWT might therefore cause degenerative changes in hyaline cartilage as they are found in initial OA.

Uninephrectomy reduces 11β-hydroxysteroid dehydrogenase type 1 and type 2 concomitantly with an increase in blood pressure in rats

Renal allograft donors are at risk of developing hypertension. Here, we hypothesized that this risk is at least in part explained by an enhanced intracellular availability of 11β-hydroxyglucocorticoids due to an increased 11β-hydroxysteroid dehydrogenase type 1 enzyme (11β-HSD1), an intracellular prereceptor activator of biologically inactive 11-ketocorticosteroids in the liver, and/or a diminished 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2), an inactivator of 11β-hydroxyglucocorticoids in the kidney. To test this hypothesis, uninephrectomized (UNX) (n=9) and sham-operated (n=10) adult Sprague-Dawley rats were investigated. Mean arterial blood pressure and heart rate were measured continuously by telemetry for 6 days in week 5 after UNX. The mRNA of 11β-Hsd1 and 11β-Hsd2 in liver and kidney tissues were assessed by RT-PCR and the 11β-HSD activities were directly quantified in their corresponding tissues by determining the ratios of (tetrahydrocorticosterone+5α-tetrahydrocorticosterone)/tetrahydrodehydrocorticosterone ((THB+5α-THB)/THA) and of corticosterone/dehydrocorticosterone (B/A) by gas chromatography-mass spectrometry. The apparent total body activities of 11β-HSD1 and 11β-HSD2 were estimated using the urinary and plasma ratios of (THB+5α-THB)/THA and B/A. Mean arterial blood pressure was increased after UNX when compared with sham operation. Hepatic mRNA content of 11β-Hsd1 and hepatic, plasma, and urinary ratios of (THB+5α-THB)/THA were decreased after UNX, indicating diminished access of glucocorticoids to its receptors. In renal tissue, 11β-Hsd2 mRNA was reduced and B/A ratios measured in kidney, plasma, and urine were increased, indicating reduced 11β-HSD2 activity and enhanced access of glucocorticoids to mineralocorticoid receptors. Both 11β-HSD1 and 11β-HSD2 are downregulated after UNX in rats, a constellation considered to induce hypertension.

Immediate and delayed transplantation of mesenchymal stem cells improve muscle force after skeletal muscle injury in rats

Mesenchymal stem cell (MSC) therapy is a promising approach for regaining muscle function after trauma. Prior to clinical application, the ideal time of transplantation has to be determined. We investigated the effects of immediate and delayed transplantation. Sprague-Dawley rats received a crush trauma to the left soleus muscle. Treatment groups were transplanted locally with 2 × 10(6) autologous MSCs, either immediately or 7 days after trauma. Saline was used as sham therapy. Contraction force tests and histological analyses were performed 4 weeks after injury. GFP-labelled MSCs were followed after transplantation. The traumatized soleus muscles of the sham group displayed a reduction of twitch forces to 36 ± 17% and of tetanic forces to 29 ± 11% of the non-injured right control side, respectively. Delayed MSC transplantation resulted in a significant improvement of contraction maxima in both stimulation modes (twitch, p = 0.011; tetany, p = 0.014). Immediate transplantation showed a significant increase in twitch forces to 59 ± 17% (p = 0.043). There was no significant difference in contraction forces between muscles treated by immediate and delayed cell transplantation. We were able to identify MSCs in the interstitium of the injured muscles up to 4 weeks after transplantation. Despite the fundamental differences of the local environment, which MSCs encounter after transplantation, similar results could be obtained with respect to functional muscle regeneration. We believe that transplanted MSCs residing in the interstitial compartment evolve their regenerative capabilities through paracrine pathways. Our data suggest a large time window of the therapeutical measures.

Noninvasive Doppler-derived myocardial performance index in rats with myocardial infarction: validation and correlation by conductance catheter

The rodent model of myocardial infarction (MI) is extensively used in heart failure studies. However, long-term follow-up of echocardiographic left ventricular (LV) function parameters such as the myocardial performance index (MPI) and its ratio with the fractional shortening (LVFS/MPI) has not been validated in conjunction with invasive indexes, such as those derived from the conductance catheter (CC). Sprague-Dawley rats with left anterior descending coronary artery ligation (MI group, n = 9) were compared with a sham-operated control group (n = 10) without MI. Transthoracic echocardiography (TTE) was performed every 2 wk over an 8-wk period, after which classic TTE parameters, especially MPI and LVFS/MPI, were compared with invasive indexes obtained by using a CC. Serial TTE data showed significant alterations in the majority of the noninvasive functional and structural parameters (classic and novel) studied in the presence of MI. Both MPI and LVFS/MPI significantly (P < 0.05 for all reported values) correlated with body weight (r = -0.58 and 0.76 for MPI and LVFS/MPI, respectively), preload recruitable stroke work (r = -0.61 and 0.63), LV end-diastolic pressure (LVEDP) (r = 0.82 and -0.80), end-diastolic volume (r = 0.61 and -0.58), and end-systolic volume (r = 0.46 and -0.48). Forward stepwise linear regression analysis revealed that, of all variables tested, LVEDP was the only independent determinant of MPI (r = 0.84) and LVFS/MPI (r = 0.83). We conclude that MPI and LVFS/MPI correlate strongly and better than the classic noninvasive TTE parameters with established, invasively assessed indexes of contractility, preload, and volumetry. These findings support the use of these two new noninvasive indexes for long-term analysis of the post-MI LV remodeling.

Continuous thoracic epidural anesthesia improves gut mucosal microcirculation in rats with sepsis

Microcirculatory dysfunction contributes significantly to tissue hypoxia and multiple organ failure in sepsis. Ischemia of the gut and intestinal hypoxia are especially relevant for the evolution of sepsis because the mucosal barrier function may be impaired, leading to translocation of bacteria and toxins. Because sympathetic blockade enhances intestinal perfusion under physiologic conditions, we hypothesized that thoracic epidural anesthesia (TEA) may attenuate microcirculatory perturbations during sepsis. The present study was designed as a prospective and controlled laboratory experiment to assess the effects of continuous TEA on the mucosal microcirculation in a cecal ligation and perforation model of sepsis in rats. Anesthetized Sprague-Dawley rats underwent laparotomy and cecal ligation and perforation to induce sepsis. Subsequently, either bupivacaine 0.125% (n = 10) or isotonic sodium chloride solution (n = 9) was continuously infused via the thoracic epidural catheter for 24 h. In addition, a sham laparotomy was carried out in eight animals. Intravital videomicroscopy was then performed on six to ten villi of ileum mucosa. The capillary density was measured as areas encircled by perfused capillaries, that is, intercapillary areas. The TEA accomplished recruitment of microcirculatory units in the intestinal mucosa by decreasing total intercapillary areas (1,317 +/- 403 vs. 1,001 +/- 236 microm2) and continuously perfused intercapillary areas (1,937 +/- 512 vs. 1,311 +/- 678 microm2, each P < 0.05). Notably, TEA did not impair systemic hemodynamic variables beyond the changes caused by sepsis itself. Therefore, sympathetic blockade may represent a therapeutic option to treat impaired microcirculation in the gut mucosa resulting from sepsis. Additional studies are warranted to assess the microcirculatory effects of sympathetic blockade on other splanchnic organs in systemic inflammation.

Baclofen and gamma-hydroxybutyrate differentially altered behavior, EEG activity and sleep in rats.

OBJECTIVES Animal and human studies have shown that sleep may have an impact on functional recovery after brain damage. Baclofen (Bac) and gamma-hydroxybutyrate (GHB) have been shown to induce physiological sleep in humans, however, their effects in rodents are unclear. The aim of this study is to characterize sleep and electroencelphalogram (EEG) after Bac and GHB administration in rats. We hypothesized that both drugs would induce physiological sleep. METHODS Adult male Sprague-Dawley rats were implanted with EEG/electromyogram (EMG) electrodes for sleep recordings. Bac (10 or 20 mg/kg), GHB (150 or 300 mg/kg) or saline were injected 1 h after light and dark onset to evaluate time of day effect of the drugs. Vigilance states and EEG spectra were quantified. RESULTS Bac and GHB induced a non-physiological state characterized by atypical behavior and an abnormal EEG pattern. After termination of this state, Bac was found to increase the duration of non-rapid eye movement (NREM) and rapid eye movement (REM) sleep (∼90 and 10 min, respectively), reduce sleep fragmentation and affect NREM sleep episode frequency and duration (p<0.05). GHB had no major effect on vigilance states. Bac drastically increased EEG power density in NREM sleep in the frequencies 1.5-6.5 and 9.5-21.5 Hz compared to saline (p<0.05), while GHB enhanced power in the 1-5-Hz frequency band and reduced it in the 7-9-Hz band. Slow-wave activity in NREM sleep was enhanced 1.5-3-fold during the first 1-2 h following termination of the non-physiological state. The magnitude of drug effects was stronger during the dark phase. CONCLUSION While both Bac and GHB induced a non-physiological resting state, only Bac facilitated and consolidated sleep, and promoted EEG delta oscillations thereafter. Hence, Bac can be considered a sleep-promoting drug and its effects on functional recovery after stroke can be evaluated both in humans and rats.

Histological evidence of delayed ischemic brain tissue damage in the rat double-hemorrhage model

The rat double-SAH model is one of the standard models to simulate delayed cerebral vasospasm (CVS) in humans. However, the proof of delayed ischemic brain damage is missing so far. Our objective was, therefore, to determine histological changes in correlation with the development of symptomatic and perfusion weighted imaging (PWI) proven CVS in this animal model. CVS was induced by injection of autologous blood in the cisterna magna of 22 Sprague-Dawley rats. Histological changes were analyzed on day 3 and day 5. Cerebral blood flow (CBF) was assessed by PWI at 3 tesla magnetic resonance (MR) tomography. Neuronal cell count did not differ between sham operated and SAH rats in the hippocampus and the cerebral cortex on day 3. In contrast, on day 5 after SAH the neuronal cell count was significantly reduced in the hippocampus (p<0.001) and the inner cortical layer (p=0.03). The present investigation provides quantitative data on brain tissue damage in association with delayed CVS for the first time in a rat SAH model. Accordingly, our data suggest that the rat double-SAH model may be suitable to mimic delayed ischemic brain damage due to CVS and to investigate the neuroprotective effects of drugs.

Electrospun PLLA nanofiber scaffolds and their use in combination with BMP-2 for reconstruction of bone defects

Introduction Adequate migration and differentiation of mesenchymal stem cells is essential for regeneration of large bone defects. To achieve this, modern graft materials are becoming increasingly important. Among them, electrospun nanofiber scaffolds are a promising approach, because of their high physical porosity and potential to mimic the extracellular matrix (ECM). Materials and Methods The objective of the present study was to examine the impact of electrospun PLLA nanofiber scaffolds on bone formation in vivo, using a critical size rat calvarial defect model. In addition we analyzed whether direct incorporation of bone morphogenetic protein 2 (BMP-2) into nanofibers could enhance the osteoinductivity of the scaffolds. Two critical size calvarial defects (5 mm) were created in the parietal bones of adult male Sprague-Dawley rats. Defects were either (1) left unfilled, or treated with (2) bovine spongiosa, (3) PLLA scaffolds alone or (4) PLLA/BMP-2 scaffolds. Cranial CT-scans were taken at fixed intervals in vivo. Specimens obtained after euthanasia were processed for histology, histomorphometry and immunostaining (Osteocalcin, BMP-2 and Smad5). Results PLLA scaffolds were well colonized with cells after implantation, but only showed marginal ossification. PLLA/BMP-2 scaffolds showed much better bone regeneration and several ossification foci were observed throughout the defect. PLLA/BMP-2 scaffolds also stimulated significantly faster bone regeneration during the first eight weeks compared to bovine spongiosa. However, no significant differences between these two scaffolds could be observed after twelve weeks. Expression of osteogenic marker proteins in PLLA/BMP-2 scaffolds continuously increased throughout the observation period. After twelve weeks osteocalcin, BMP-2 and Smad5 were all significantly higher in the PLLA/BMP-2 group than in all other groups. Conclusion Electrospun PLLA nanofibers facilitate colonization of bone defects, while their use in combination with BMP-2 also increases bone regeneration in vivo and thus combines osteoconductivity of the scaffold with the ability to maintain an adequate osteogenic stimulus.

High salt intake down-regulates colonic mineralocorticoid receptors, epithelial sodium channels and 11β-hydroxysteroid dehydrogenase type 2

Besides the kidneys, the gastrointestinal tract is the principal organ responsible for sodium homeostasis. For sodium transport across the cell membranes the epithelial sodium channel (ENaC) is of pivotal relevance. The ENaC is mainly regulated by mineralocorticoid receptor mediated actions. The MR activation by endogenous 11β-hydroxy-glucocorticoids is modulated by the 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2). Here we present evidence for intestinal segment specific 11β-HSD2 expression and hypothesize that a high salt intake and/or uninephrectomy (UNX) affects colonic 11β-HSD2, MR and ENaC expression. The 11β-HSD2 activity was measured by means of 3H-corticosterone conversion into 3H-11-dehydrocorticosterone in Sprague Dawley rats on a normal and high salt diet. The activity increased steadily from the ileum to the distal colon by a factor of about 3, an observation in line with the relevance of the distal colon for sodium handling. High salt intake diminished mRNA and protein of 11β-HSD2 by about 50% (p<0.001) and reduced the expression of the MR (p<0.01). The functionally relevant ENaC-β and ENaC-γ expression, a measure of mineralocorticoid action, diminished by more than 50% by high salt intake (p<0.001). The observed changes were present in rats with and without UNX. Thus, colonic epithelial cells appear to contribute to the protective armamentarium of the mammalian body against salt overload, a mechanism not modulated by UNX.

Sleep deprivation before stroke is neuroprotective: A pre-ischemic conditioning related to sleep rebound

BACKGROUND AND AIM: We have previously shown in a rat model of focal cerebral ischemia that sleep deprivation after stroke onset aggravates brain damage. Others reported that sleep deprivation prior to stroke is neuroprotective. The main aim of this study was to test the hypothesis that the neuroprotection may be related to an increase in sleep (sleep rebound) during the acute phase of stroke. METHODS: Male Sprague Dawley rats (n=36) were subjected to continuous polygraphic recordings for baseline, total sleep deprivation (TSD), and 24h after ischemia. TSD for 6h was performed by gentle handling and immediately followed by ischemia. Focal cerebral ischemia was induced by permanent occlusion of distal branches of the middle cerebral artery. Control experiments included ischemia without SD (nSD) and sham surgery with TSD (n=6/group). RESULTS: Shortly after stroke, the amount of slow wave sleep (SWS) and paradoxical sleep (PS) increased significantly (p<0.05) in the TSD/ischemia, resulting in an increase in the total sleep time by 30% compared to baseline, or by 20% compared with the nSD/ischemia group. The infarct volume decreased significantly by 50% in the TSD/ischemia compared to nSD group (p<0.02). Removal of sleep rebound by allowing TSD-rats sleep for 24h before ischemia eliminated the reduction in the infarct size. CONCLUSION PRESTROKE: Sleep deprivation results in sleep rebound and reduces brain damage. Sleep rebound may be causally related to the neuroprotection.

Lactate, not glucose, up-regulates mitochondrial oxygen consumption both in sham and lateral fluid percussed rat brains

OBJECTIVE: Failure of energy metabolism after traumatic brain injury may be a major factor limiting outcome. Although glucose is the primary metabolic substrate in the healthy brain, the well documented surge in tissue lactate after traumatic brain injury suggests that lactate may provide an energy need that cannot be met by glucose. We hypothesized, therefore, that administration of lactate or the combination of lactate and supraphysiological oxygen may improve mitochondrial oxidative respiration in the brain after rat fluid percussion injury. We measured oxygen consumption (VO2) to determine what effects glucose, lactate, oxygen, and the combination of lactate and oxygen have on mitochondrial respiration in both injured and uninjured rat brain tissue. METHODS: Anesthetized Sprague-Dawley rats were intubated and ventilated with either 0.21 or 1.0 fraction of inspired oxygen (FIO2). Brain tissue from acute sham animals was subjected in vitro to 1.1 mM, 12 mM and 100 mM concentrations of glucose and L-lactate. In another group, injury (fluid percussion injury of 2.5 +/- 0.02 atmospheres) was induced over the left hemisphere. The VO2 of mug amounts of brain tissues were measured in a microrespirometry system (Cartesian diver). RESULTS: The VO2 was found to be independent of glucose concentrations, but dose-dependent for lactate. Moreover, the lactate dependent VO2s were all significantly higher than those generated by glucose. Injured rats on FIO2 0.21 had brain tissue VO2 rates that were significantly lower than those of shams or preinjury levels. In injured rats treated with FIO2 1.0, the reduction in VO2 levels was prevented. Injured rats that received an intravenous infusion of 100 mM lactate had VO2 rates that were significantly higher than those obtained with FIO2 1.0. Combined treatment further boosted the lactate generated VO2 rates by approximately 15%. CONCLUSION: Glucose sustains mitochondrial respiration at a low level "fixed" rate because, despite increasing its concentration nearly 100-fold, it cannot up-regulate VO2 after fluid percussion injury. Lactate produces a dose-dependent VO2 response, possibly enabling mitochondria to meet the increased energy needs of the injured brain.

The effect of a myocardial infarction on the normalized time-varying elastance curve

It has been suggested that the shape of the normalized time-varying elastance curve [E(n)(t(n))] is conserved in different cardiac pathologies. We hypothesize, however, that the E(n)(t(n)) differs quantitatively after myocardial infarction (MI). Sprague-Dawley rats (n = 9) were anesthetized, and the left anterior descending coronary artery was ligated to provoke the MI. A sham-operated control group (CTRL) (n = 10) was treated without the MI. Two months later, a conductance catheter was inserted into the left ventricle (LV). The LV pressure and volume were measured and the E(n)(t(n)) derived. Slopes of E(n)(t(n)) during the preejection period (alpha(PEP)), ejection period (alpha(EP)), and their ratio (beta = alpha(EP)/alpha(PEP)) were calculated, together with the characteristic decay time during isovolumic relaxation (tau) and the normalized elastance at end diastole (E(min)(n)). MI provoked significant LV chamber dilatation, thus a loss in cardiac output (-33%), ejection fraction (-40%), and stroke volume (-30%) (P < 0.05). Also, it caused significant calcium increase (17-fold), fibrosis (2-fold), and LV hypertrophy. End-systolic elastance dropped from 0.66 +/- 0.31 mmHg/microl (CTRL) to 0.34 +/- 0.11 mmHg/microl (MI) (P < 0.05). Normalized elastance was significantly reduced in the MI group during the preejection, ejection, and diastolic periods (P < 0.05). The slope of E(n)(t(n)) during the alpha(PEP) and beta were significantly altered after MI (P < 0.05). Furthermore, tau and end-diastolic E(min)(n) were both significantly augmented in the MI group. We conclude that the E(n)(t(n)) differs quantitatively in all phases of the heart cycle, between normal and hearts post-MI. This should be considered when utilizing the single-beat concept.

Effect of oral D-tagatose on liver volume and hepatic glycogen accumulation in healthy male volunteers

Standard toxicity tests with high levels of D-tagatose showed a reversible enlargement of the liver in Sprague-Dawley rats without increase of liver enzymes. The present study tests the hypotheses that partial substitution of dietary sucrose by D-tagatose for 28 days increases the volume of human liver and the concentration of liver glycogen. Twelve healthy, male volunteers were studied in a double-blind crossover study with ingestion of D-tagatose (3x15 g daily) and placebo (sucrose, 3x15 g daily) for periods of 28 days each. Liver volume and glycogen concentration have been determined by magnetic resonance (MR) imaging and spectroscopy, which were accompanied by routine medical examinations. MR examinations before and after the treatments revealed no effects (P>0.05) of treatment, period, or subject for changes in liver volume or glycogen concentration. A steady increase of liver volumes, independent of the D-tagatose or placebo intake, has been observed over the study in parallel with a slight increase in body weight. The treatment with D-tagatose was not associated with clinically relevant changes of the examined clinico-chemical and hematological parameters, including liver enzymes and uric acid.

Influence of inspired oxygen on glucose-lactate dynamics after subdural hematoma in the rat

The mechanisms causing brain damage after acute subdural hematoma (SDH) are poorly understood. A decrease in cerebral blood flow develops immediately after the hematoma forms, thus reducing cerebral oxygenation. This in turn may activate mitochondrial failure and tissue damage leading to ionic imbalance and possibly to cellular breakdown. The purpose of this study was to test whether a simple therapeutic measure, namely increased fraction of inspired oxygen (FiO2 100), and hence increased arterial and brain tissue oxygen tension, can influence brain glucose and lactate dynamics acutely after subdural hematoma in the rat. Twenty-five male Sprague-Dawley anesthetized rats were studied before, during and after induction of the SDH in two separate groups. The Oxygen group (n = 10) was ventilated with 100% oxygen immediately after induction of the SDH. The Air group (n = 10) was ventilated during the entire study with 21% oxygen. Brain microdialysate samples were analyzed for glucose and lactate. All rats were monitored with femoral arterial blood pressure catheters, arterial blood gas analysis, arterial glucose, lactate and end tidal CO2 (EtCO2). Five male Sprague-Dawley rats were sham operated to measure the effect of oxygen challenge on glucose-lactate dynamics without injury. Arterial oxygen tension in the Oxygen group was 371 +/- 30 mmHg and was associated with significantly greater increase in dialysate lactate in the first 30 min after induction of SDH. Dialysate glucose initially dropped in both groups, after SDH, but then reverted significantly faster to values above baseline in the Oxygen group. Changes in ventilatory parameters had no significant effect on dialysate glucose and lactate parameters in the sham group. Extracellular dialysate lactate and glucose are influenced by administration of 100% O2 after SDH. Dialysate glucose normalizes significantly quicker upon 100% oxygen ventilation. We hypothesize that increased neural tissue oxygen tension, in presence of reduced regional CBF, and possibly compromised mitochondrial function, after acute SDH results in upregulation of rate-limiting enzyme systems responsible for both glycolytic and aerobic metabolism. Similar changes have been seen in severe human head injury, and suggest that a simple therapeutic measure, such as early ventilation with 100% O2, may improve cerebral energy metabolism, early after SDH. Further studies to measure the generation of adenosine triphosphate (ATP) are needed to validate the hypothesis.