Magnetic Resonance Spectroscopy

Magnetic resonance spectroscopy (MRS) is noninvasive and may be readily combined with magnetic resonance imaging (MRI). Attention has focussed on proton (¹H) and phosphorus (³¹P) MRS, and studies have been undertaken by using single voxels or many voxels simultaneously (chemical-shift imaging, magnetic resonance spectroscopic imaging). The latter is more difficult and prone to artefact but potentially yields significantly more information. ¹H MRS has principally yielded data on concentrations of N-acetyl aspartate (NAA), choline, creatine, and phosphocreatine. NAA is located primarily within neurons, and reduction of the ratio of NAA to choline, creatine, and phosphocreatine is a marker of neu-ronal loss and dysfunction. This technique may be useful as a noninvasive tool for localizing epileptogenic foci, but its role requires further evaluation. As with all functional imaging methods, coregistration with high-quality MRI is essential for interpreting data. ¹H MRS can be used also to estimate cerebral concentrations of several neurotrans-mitters: glutamate, glutamine, and γ-aminobutyric acid (GABA). This may prove useful for characterizing the neurometabolic profiles of patients with different epilepsy syndromes and for evaluating the effects of medical and surgical treatments. ³¹P MRS can detect adenosine tri-phosphate, phosphodiesters, phosphomonoesters, phosphocreatine, and inorganic phosphate, and estimate intra-cerebral pH. Abnormalities that have been associated with epileptogenic brain areas include increased inorganic phosphate, reduced phosphomonoesters, and increased pH. Only small numbers of patients have been studied, however, so that conclusions are not definitive, and the clinical role of this technique is not yet established.     

Quantitative magnetic resonance spectroscopy of schizophrenia: relationship between decreased N-acetylaspartate and frontal lobe dysfunction

Numerous studies using proton magnetic resonance spectroscopy (1H-MRS) have detected signal changes in schizophrenia. However, most studies investigated relative concentrations such as N-acetylaspartate/creatine plus phosphocreatine (NAA/Cre) and choline-containing compounds/creatine plus phosphocreatine (Cho/Cre), and individual metabolite concentrations have not been clarified. Using absolute quantification measurement of 1H-MRS, the aim of the present paper was to demonstrate the changes in metabolite concentrations in the frontal lobe of patients with chronic schizophrenia. The 1H-MRS was performed in the left frontal lobe in 14 patients with schizophrenia and in 13 healthy comparison subjects. Individual MRS peak concentration was quantified based on a frequency-domain fitting program: LCModel. The scores on the Positive and Negative Symptoms Scale and Wisconsin Card Sorting Test were used for clinical assessment. The NAA concentration was reduced in schizophrenic patients (average, 7.94 mmol/L, t=2.28, P<0.05) compared with healthy subjects (average=8.45 mmol/L) while choline, creatine or NAA/Cre ratio did not show any differences. The reduction in NAA concentration had a significant correlation with the severity of negative symptoms (r=-0.536, P<0.05) and poor performance in Wisconsin Card Sorting Test (r=-0.544, P<0.05). Using quantitative MRS, decreased NAA concentration was confirmed in the left frontal lobe of schizophrenic patients and was demonstrated to be correlated with negative symptoms and cognitive dysfunction in schizophrenia.     

Cardiac and skeletal muscle involvement in myotonic dystrophy type 2 (DM2): a quantitative 31P-MRS and MRI study

In myotonic dystrophy type 2 (DM2/PROMM), cardiac muscle involvement is usually more benign than in DM1, but clinically severe cardiomyopathy has been reported in some patients. Using a novel method of magnetic resonance spectroscopy (MRS), we examined the left ventricular myocardium and the left gastrocnemius muscle in 11 unselected DM2/PROMM patients without overt cardiac disease. Data on cardiac morphology and function were obtained by gradient echo two-dimensional cine magnetic resonance imaging (MRI); no significant differences were found between DM2 patients and healthy controls, but using a median split approach older patients showed mildly increased left ventricular (LV) volumes, i.e., 59% increase of end-systolic volume index (ESVI) and 35% increase of end-diastolic volume index (EDVI), and an increase of LV mass (26%). On cardiac MRS, DM2/PROMM patients showed a reduction of phosphocreatine (PCr) and adenosine triphosphate (ATP) by 25 and 20% compared to matched healthy controls. No significant differences were found between younger and older patients. In skeletal muscle of the DM2 patients, no significant decrease of PCr and ATP concentrations was found. However, in older patients, who commonly show overt hip flexor muscle weakness, we observed reduced values for PCr and ATP. Our MRS and MRI findings reveal evidence for subclinical cardiomyopathy in DM2/PROMM patients without overt heart disease. Future prospective studies are needed to clarify the risk of developing overt cardiac disease in DM2 and to define prognostic factors.     

Multivoxel proton magnetic resonance spectroscopy in facioscapulohumeral muscular dystrophy

Introduction: Facioscapulohumeral muscular dystrophy (FSHD) is a hereditary disorder that causes progressive muscle wasting. This study evaluates the use of proton magnetic resonance spectroscopy (¹H MRS) as a biomarker of muscle strength and function in FSHD. Methods: Thirty‐six individuals with FSHD and 15 healthy controls underwent multivoxel ¹H MRS of a cross‐section of the mid‐thigh. Concentrations of creatine, intramyocellular and extramyocellular lipids, and trimethylamine (TMA)‐containing compounds in skeletal muscle were calculated. Metabolite concentrations for individuals with FSHD were compared with those of controls. The relationship between metabolite concentrations and muscle strength was also examined. Results: The TMA/creatine (Cr) ratio in individuals with FSHD was reduced compared with controls. The TMA/Cr ratio in the hamstrings also showed a moderate linear correlation with muscle strength. Discussion: ¹H MRS offers a potential method of detecting early muscle pathology in FSHD prior to the development of fat infiltration. Muscle Nerve 57 : 958–963, 2018     

H magnetic resonance spectroscopy in the investigation of intractable epilepsy

We have been using proton magnetic resonance spectroscopy (¹H MRS) in the investigation of adults and children with intractable epilepsy. Spectra were obtained from 2 × 2 times 2 cm cubes in the medial region of the temporal lobe, and were analyzed on the basis of signals from N-acetylaspartate (NAA), creatine+phosphocreatine (Cr), and choline-containing compounds (Cho). In comparison with control subjects, the epilepsy patients as a group show significant reductions in the NAA signal and in the NAA/Cho + Cr ratio, with increases in the Cho and Cr signals. The reduction in NAA is interpreted in terms of neuronal loss or damage, while the increase in Cr and Cho signals may be a reflection of reactive astrocytosis.     

In Vivo 1H Magnetic Resonance Spectroscopic Measurement of Brain Glycine Levels in Nonketotic Hyperglycinemia

Nonketotic hyperglycinemia (NKH) is an autosomal recessive disorder of glycine metabolism. Defective glycine cleavage causes elevated concentrations of glycine in plasma, urine, and cerebrospinal fluid. A longitudinal study using magnetic resonance imaging (MRI) and single-voxel 1H magnetic resonance spectroscopy (MRS) was performed on an infant with the typical clinical picture of NKH. He was examined twice during the course of treatment with sodium benzoate and dextromethorphan. At the age of 10 months, MRI showed normal brain structure, while MRS detected a prominent glycine peak in the brain. Repeat MRS at the age of 13 months showed a small increase in glycine peak and a prominent glutamate/glutamine peak not previously detected. The MRS measurements were consistent with the slight increase in blood glycine level and the elevation in glutamine level, indicating that 1HMRS can be a valuable tool in the diagnosis and monitoring of treatment effects in patients with NKH.     

Creatine kinase B-driven energy transfer in the brain is important for habituation and spatial learning behaviour,mossy fibre field size and determination of seizure susceptibility

Creatine kinases are important in maintaining cellular-energy homeostasis, and neuroprotective effects have been attributed to the administration of creatine and creatine-like compounds. Herein we examine whether ablation of the cytosolic brain-type creatine kinase (B-CK) in mice has detrimental effects on brain development, physiological integrity or task performance. Mice deficient in B-CK (B-CK-/-) showed no gross abnormalities in brain anatomy or mitochondrial ultrastructure, but had a larger intra- and infrapyramidal mossy fibre area. Nuclear magnetic resonance spectroscopy revealed that adenosine triphosphate (ATP) and phosphocreatine (PCr) levels were unaffected, but demonstrated an apparent reduction of the PCr left arrow over right arrow ATP phosphorus exchange capacity in these mice. When assessing behavioural characteristics B-CK-/- animals showed diminished open-field habituation. In the water maze, adult B-CK-/- mice were slower to learn, but acquired the spatial task. This task performance deficit persisted in 24-month-old, aged B-CK-/- mice, on top of the age-related memory decline normally seen in old animals. Finally, a delayed development of pentylenetetrazole-induced seizures (creating a high-energy demand) was observed in B-CK-/- mice. It is suggested that the persistent expression of the mitochondrial isoform ubiquitous mitochondrial CK (UbCKmit) in the creatine/phospho-creatine shuttle provides compensation for the loss of B-CK in the brain. Our studies indicate a role for the creatine-phosphocreatine/CK circuit in the formation or maintenance of hippocampal mossy fibre connections, and processes that involve habituation, spatial learning and seizure susceptibility. However, for fuelling of basic physiological activities the role of B-CK can be compensated for by other systems in the versatile and robust metabolic-energy network of the brain.     

MRS Findings in Cerebral Coenurosis due to Taenia Multiceps

Cerebral coenurosis due to Taenia multiceps is a rare infection with no case reports from India. A 55‐year‐old male patient had presented with progressive symptoms of hemiparesis of 1‐year duration. Magnetic resonance imaging (MRI) with magnetic resonance spectroscopy (MRS) of the lesion was performed that showed a septated cystic lesion in left parieto‐occipital lobe. Multivoxel MRS through the lesion was performed using repetition time of 1500 ms and time to echo of 144 ms at 3T MRI. MRS showed mildly elevated choline (Cho), depressed creatine (Cr), and N‐acetyl aspartate (NAA), a large peak of lactate, pyruvate, and acetate peaks. To best of our knowledge, there has been no reported case of in vivo proton MRS finding ever reported. We present MRS findings in this operatively proven case of T. multiceps cyst of the brain.     

In vivo phosphocreatine and ATP in piglet cerebral gray and white matter during seizures

The creatine kinase (CK) reaction is thought to be important in coupling ATP metabolism and regulating ADP concentration in tissues with high and variable ATP turnover, including cerebral gray matter (GM). There is low phosphocreatine (PCr), low CK reaction rates, and high mitochondrial CK (MiCK) isoenzyme activity in GM compared to white matter (WM). To compare the CK reaction in GM and WM when ATP metabolism is high, CK reactants and reaction rates were measured in predominantly GM and WM slices in vivo in 2 and 14-day old piglets during pentylenetetrazole (PTZ) seizures using ³¹P nuclear magnetic resonance (NMR) 1-dimensional chemical shift imaging (CSI). Arterial pressure, temperature, and blood gasses were stable at both ages. Before seizures, the PCr/nucleoside triphosphate (NTP) ratio was higher in WM than GM at both ages with a developmental increase seen in WM. The CK reaction rate constant increased in both regions between 2 and 14 days. During seizures, PCr/NTP increased in GM at 14 days due to increased PCr while the ratio and PCr decreased in WM. The NTP was more stable in WM and GM at both ages. The CK reaction rate decreased in both regions more at 2 than at 14 days. Thus, brain ATP, deduced from NTP, is stable during seizures in the piglet. In GM stable ATP is associated with a unique increase in PCr concentration.     

The earliest MR imaging and proton MR spectroscopy abnormalities in adult-onset Krabbe disease

BACKGROUND: Adult-onset Krabbe disease is an uncommon form of leukodystrophy. Its magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) manifestations are not well documented. AIM OF THE STUDY: To describe early MR findings in adult-onset Krabbe disease. MATERIALS AND METHODS: A 28-year-old woman who had spastic paraparesis and a 5-year history of gait problems underwent MRI of the brain and cervical spine. Proton MRS was performed at 1.5 T using a short echo time. Metabolites were analyzed in the areas of MR signal abnormalities and normal-appearing brain. Six healthy volunteers were examined as controls. RESULTS: MRI revealed changes in the upper corticospinal tracts, splenium and, minimally, adjacent to the atria of the lateral ventricles. MRS showed decreased creatine, choline, N-acetylaspartate and glutamate and probably elevated lactate in the upper corticospinal tract but not in the normal-appearing frontal lobe. The spinal cord was thin. Laboratory tests verified Krabbe disease. CONCLUSIONS: These results indicate early involvement of the upper corticospinal tract in adult-onset Krabbe disease. The cases reported earlier had imaging changes indicating a more advanced disease or no MR findings. Thinning of the spinal cord is a new finding in Krabbe disease.     

Altered brain phosphocreatine and ATP regulation when mitochondrial creatine kinase is absent.

In cerebral gray matter, ATP concentration is closely maintained despite rapid, large increases in turnover and low substrate reserves. As seen in vivo by (31)P nuclear magnetic resonance (NMR) spectroscopy, brain ATP is stable early in seizures, a state of high energy demand, and in mild hypoxia, a state of substrate deficiency. Like other tissues with high and variable ATP turnover, cerebral gray matter has high phosphocreatine (PCr) concentration and both cytosolic and mitochondrial creatine kinase (UbMi-CK) isoenzymes. To understand the physiology of brain creatine kinases, we used (31)P NMR to study PCr and ATP regulation during seizures and hypoxia in mice with targeted deletion of the UbMi-CK gene. The baseline CK reaction rate constant (k) was higher in mutants than wild-types. During seizures, PCr and ATP decreased in mutants but not in wild-types. The k-value for the CK catalyzed reaction rate increased in wild-types but not in the mutants. Hypoxic mutants and wild-types showed similar PCr losses and stable ATP. During recovery from hypoxia, brain PCr and ATP concentrations returned to baseline in wild-types but were 20% higher than baseline in the mutants. We propose that UbMi-CK couples ATP turnover to the CK catalyzed reaction rate and regulates ATP concentration when synthesis is increased.     

Reduced brain glutamine in female varsity rugby athletes after concussion and in non‐concussed athletes after a season of play

The purpose of this study was to use non‐invasive proton magnetic resonance spectroscopy (MRS) and diffusion tensor imaging (DTI) to monitor changes in prefrontal white matter metabolite levels and tissue microstructure in female rugby players with and without concussion (ages 18–23, n = 64). Evaluations including clinical tests and 3 T MRI were performed at the beginning of a season (in‐season) and followed up at the end of the season (off‐season). Concussed athletes were additionally evaluated 24–72 hr (n = 14), three months (n = 11), and six months (n = 8) post‐concussion. Reduced glutamine at 24–72 hr and three months post‐concussion, and reduced glutamine/creatine at three months post‐concussion were observed. In non‐concussed athletes (n = 46) both glutamine and glutamine/creatine were lower in the off‐season compared to in‐season. Within the MRS voxel, an increase in fractional anisotropy (FA) and decrease in radial diffusivity (RD) were also observed in the non‐concussed athletes, and correlated with changes in glutamine and glutamine/creatine. Decreases in glutamine and glutamine/creatine suggest reduced oxidative metabolism. Changes in FA and RD may indicate neuroinflammation or re‐myelination. The observed changes did not correlate with clinical test scores suggesting these imaging metrics may be more sensitive to brain injury and could aid in assessing recovery of brain injury from concussion.     

Proton magnetic resonance spectroscopy in childhood brainstem lesions

Background Diagnosis of brainstem lesions in children based on magnetic resonance imaging alone is a challenging problem. Magnetic resonance spectroscopy (MRS) is a noninvasive technique for spatial characterization of biochemical markers in tissues and gives information regarding cell membrane proliferation, neuronal damage, and energy metabolism. Methods We measured the concentrations of biochemical markers in five children with brainstem lesions and evaluated their potential diagnostic significance. Images and spectra were acquired on a 1.5-T imager. The concentrations of N-acetylaspartate, tetramethylamines (e.g., choline), creatine, phosphocreatine, lactate, and lipids were measured within lesions located at the brainstem using Point-resolved spectroscopy sequences. Results Diagnosis based on localized proton spectroscopy included brainstem glioma, brainstem encephalitis, demyelination, dysmyelination secondary to neurofibromatosis type 1 (NF 1), and possible infection or radiation necrosis. In all but one patient, diagnosis was confirmed by biopsy or by clinical follow-up. Conclusions This small sample of patients suggests that MRS is important in the differential diagnosis between proliferative and nonproliferative lesions in patients without neurofibromatosis. Unfortunately, in cases of NF 1, MRS can have a rather misdiagnosis role.     

Neurochemical correlates of caudate atrophy in Huntington's disease

The precise pathogenic mechanisms of Huntington's disease (HD) are unknown but can be tested in vivo using proton magnetic resonance spectroscopy (¹H MRS) to measure neurochemical changes. The objective of this study was to evaluate neurochemical differences in HD gene mutation carriers (HGMCs) versus controls and to investigate relationships among function, brain structure, and neurochemistry in HD. Because previous ¹H MRS studies have yielded varied conclusions about HD neurochemical changes, an additional goal was to compare two ¹H MRS data analysis approaches. HGMCs with premanifest to early HD and controls underwent evaluation of motor function, magnetic resonance imaging, and localized ¹H MRS in the caudate and the frontal lobe. Analytical approaches that were tested included absolute quantitation (unsuppressed water signal as an internal reference) and relative quantification (calculating ratios of all neurochemical signals within a voxel). We identified a suite of neurochemicals that were reduced in concentration proportionally to loss of caudate volume in HGMCs. Caudate concentrations of N‐acetylaspartate (NAA), creatine, choline, and caudate and frontal lobe concentrations of glutamate plus glutamine (Glx) and glutamate were correlated with caudate volume in HGMCs. The relative, but not the absolute, quantitation approach revealed disease‐related differences; the Glx signal was decreased relative to other neurochemicals in the caudate of HGMCs versus controls. This is the first study to demonstrate a correlation among structure, function, and chemical measures in HD brain. Additionally, we demonstrate that a relative quantitation approach may enable the magnification of subtle differences between groups. Observation of decreased Glx suggests that glutamate signaling may be disrupted relatively early in HD, which has important implications for therapeutic approaches. © 2014 International Parkinson and Movement Disorder Society     

Tai Chi Improves Brain Metabolism and Muscle Energetics in Older Adults

BACKGROUND AND PURPOSE

Tai Chi is a mind‐body exercise that has been shown to improve both mental and physical health. As a result, recent literature suggests the use of Tai Chi to treat both physical and psychological disorders. However, the underlying physiological changes have not been characterized. The aim of this pilot study is to assess the changes in brain metabolites and muscle energetics after Tai Chi training in an aging population using a combined brain‐muscle magnetic resonance spectroscopy (MRS) examination.

METHODS

Six healthy older adults were prospectively recruited and enrolled into a 12‐week Tai Chi program. A brain ¹H MRS and a muscle ³¹P MRS were scanned before and after the training, and postprocessed to measure N‐acetylaspartate to creatine (NAA/Cr) ratios and phosphocreatine (PCr) recovery time. Wilcoxon‐signed rank tests were utilized to assess the differences between pre‐ and post‐Tai Chi training.

RESULTS

A significant within‐subject increase in both the NAA/Cr ratios (P = .046) and the PCr recovery time (P = .046) was observed between the baseline and the posttraining scans. The median percentage changes were 5.38% and 16.51% for NAA/Cr and PCr recovery time, respectively.

CONCLUSIONS

Our pilot study demonstrates significant increase of NAA/Cr ratios in posterior cingulate gyrus and significantly improved PCr recovery time in leg muscles in older adults following short‐term Tai Chi training, and thus provides insight into the beneficial mechanisms.     

Sex differences in glycolysis during brief, intense isometric contractions

We have previously observed less muscle fatigue in women than men under conditions of intact circulation, but similar fatigue across the sexes during local ischemia. Thus, we hypothesized that women utilize their aerobic metabolic pathways to a greater extent than do men. To test this hypothesis, we examined the extent to which different pathways of intramuscular adenosine triphosphate (ATP) production were utilized by men and women during maximal voluntary isometric contractions. Force production during 15-s and 60-s contractions were recorded in parallel sessions. In one session, central activation was assessed with electrical stimulation. In the other, phosphorus magnetic resonance spectroscopy was used to quantify muscle oxidative capacity, and the contributions of glycolysis and oxidative phosphorylation to ATP synthesis during the 60-s contraction. Fatigue and central activation were similar in men and women during both the 15-s and 60-s contractions. The rate constants of phosphocreatine recovery following the 15-s contraction were similar in men and women, indicating similar oxidative capacities. Men exhibited greater acidosis and peak glycolytic rates compared with women during the 60-s contraction, with no differences observed in creatine kinase flux or the percent of oxidative capacity utilized. We conclude that men exhibit greater in vivo glycolysis during brief, intense isometric contractions. Although this metabolic difference did not contribute to any observable differences in fatigue in the present study, these results highlight a potentially important mechanism to explain sex-related differences in muscle function.     

肌萎缩侧索硬化症病人大脑中央前回运动区磁共振波谱分析

目的 :1H MRS是否可确定ALS病人大脑皮质运动区神经元受损 ,是否适用于监测ALS病情。方法 :病例组包括 9例ALS病人。对照组包括 5例健康人 ,同时测定大脑皮质运动区的NAA、Cho、Cr。结果 :ALS病例组中NAA/Cr显著低于对照组 (P <0 0 5 ) ,Cho/Cr显著高于对照组 (P <0 0 1)。结论 :NAA/Cr下降和Cho/Cr升高 ,提示ALS病人大脑皮质运动区存在神经元破坏和鞘膜功能的异常     

Spectroscopic biomarkers of motor cortex developmental plasticity in hemiparetic children after perinatal stroke

Perinatal stroke causes hemiparetic cerebral palsy and lifelong motor disability. Bilateral motor cortices are key hubs within the motor network and their neurophysiology determines clinical function. Establishing biomarkers of motor cortex function is imperative for developing and evaluating restorative interventional strategies. Proton magnetic resonance spectroscopy (MRS) quantifies metabolite concentrations indicative of underlying neuronal health and metabolism in vivo. We used functional magnetic resonance imaging (MRI)‐guided MRS to investigate motor cortex metabolism in children with perinatal stroke. Children aged 6–18 years with MRI‐confirmed perinatal stroke and hemiparetic cerebral palsy were recruited from a population‐based cohort. Metabolite concentrations were assessed using a PRESS sequence (3T, TE = 30 ms, voxel = 4 cc). Voxel location was guided by functional MRI activations during finger tapping tasks. Spectra were analysed using LCModel. Metabolites were quantified, cerebral spinal fluid corrected and compared between groups (ANCOVA) controlling for age. Associations with clinical motor performance (Assisting Hand, Melbourne, Box‐and‐Blocks) were assessed. Fifty‐two participants were studied (19 arterial, 14 venous, 19 control). Stroke participants demonstrated differences between lesioned and nonlesioned motor cortex N‐acetyl‐aspartate [NAA mean concentration = 10.8 ± 1.9 vs. 12.0 ± 1.2, P < 0.01], creatine [Cre 8.0 ± 0.9 vs. 7.4 ± 0.9, P < 0.05] and myo‐Inositol [Ins 6.5 ± 0.84 vs. 5.8 ± 1.1, P < 0.01]. Lesioned motor cortex NAA and creatine were strongly correlated with motor performance in children with arterial but not venous strokes. Interrogation of motor cortex by fMRI‐guided MRS is feasible in children with perinatal stroke. Metabolite differences between hemispheres, stroke types and correlations with motor performance support functional relevance. MRS may be valuable in understanding the neurophysiology of developmental neuroplasticity in cerebral palsy. Hum Brain Mapp 38:1574–1587, 2017. © 2016 Wiley Periodicals, Inc.     

施普善治疗急性脑梗死的磁共振波谱成像评价

目的观察施普善对急性脑梗死患者磁共振氢质子波谱（H magnetic resonance spectroscopy,MRS）及临床症状、体征改善的影响,评价施普善治疗急性脑梗死的疗效。方法选择发病24h内的急性脑梗死患者40例,随机分为施普善治疗组20例及对照组20例。2组治疗前及治疗2周后行美国国立卫生研究院脑卒中量表评分（NIHSS评分）,应用MRS在兴趣区上测量氮-乙酰天冬氨酸（NAA）与肌酸（Cr）比值（NAA/Cr）、胆碱复合物（Cho）与肌酸（Cr）比值（Cho/Cr）及乳酸（Lac）与肌酸（Cr）比值（Lac/Cr）,并对治疗前后结果进行统计学分析。结果治疗2周后2组NIHSS评分较治疗前均有所降低,施普善治疗组较对照组下降明显（P〈0.05）,2组病人NAA/Cr较治疗前升高,但施普善治疗组较对照组升高明显（P〈0.05）,2组病人CHO/Cr及Lac/Cr均较治疗前降低,但施普善治疗组较对照组降低明显（P〈0.05）。结论施普善是一种有效的治疗急性脑梗死的神经保护剂。     

Endotoxemia causes a paradoxical intracellular pH recovery in exercising rat skeletal muscle

In resting skeletal muscle, endotoxemia causes disturbances in energy metabolism that could potentially disturb intracellular pH (pH(i)) during muscular activity. We tested this hypothesis using in situ (31)P-magnetic resonance spectroscopy in contracting rat gastrocnemius muscle. Endotoxemia was induced by injecting rats intraperitoneally at t(0) and t(0) + 24 h with Klebsiella pneumoniae endotoxin (lipopolysaccharides at 3 mg/kg) or saline vehicle. Muscle function was investigated strictly noninvasively at t(0) + 48 h through a transcutaneous electrical stimulation protocol consisting of 5.7 minutes of repeated isometric contraction at 3.3 HZ, and force production was measured with an ergometer. At rest, endotoxin treatment did not affect pH(i) and adenosine triphosphate concentration, but significantly reduced phosphocreatine and glycogen contents. Endotoxemia produced both a reduction of isometric force production and a marked linear recovery (0.08 +/- 0.01 pH unit/min) of pH(i) during the second part of the stimulation period. This recovery was not due to any phenomenon of fiber inactivation linked to development of muscle fatigue, and was not associated with any change in intracellular proton buffering, net proton efflux from the cell, or proton turnovers through creatine kinase reaction and oxidative phosphorylation. This paradoxical pH(i) recovery in exercising rat skeletal muscle under endotoxemia is likely due to slowing of glycolytic flux following the reduction in intramuscular glycogen content. These findings may be useful in the follow-up of septic patients and in the assessment of therapies.