Expression of DeltaNp73 in hippocampus of APP/PS1 transgenic mice following GFP-BMSCs transplantation

Abstract

Objective: To study the effect of hippocampal bone marrow stromal cells (GFP-BMSCs) transplantation on spatial memory and DeltaNp73 expression in APP/PS1 transgenic mice.

Methods: Twelve APP/PS1 transgenic mice randomly received either 10 μl GFP-BMSCs suspension in medium (GFP-BMSCs transplantation group) or 10 μl complete medium (sham-operated group). Learning and memory function of mice in both groups were observed and tested in Morris water maze experiment at 2 weeks after surgery. Senile plaques and DeltaNp73 protein in hippocampuses were determined by immunohistochemistry and western blot at 3 weeks after surgery, respectively.

Results: APP/PS1 mice treated with BMSCs performed significantly better on the water maze test than those in sham-operated group (P<0·05). Immunohistochemistry showed that GFP-BMSCs distributed uniformly and the number of Alzheimer’s senile plaques reduced after transplantation. Western blot showed that quantified DeltaNp73 protein expression was significantly higher in BMSCs transplantation group when compared with sham-operated group (P<0·01).

Conclusions: Our results suggest that BMSCs transplatation could retard Alzheimer’s disease (AD) like pathology and upregulate DeltaNp73 expression in hippocampuses of APP/PS1 transgenic mice. GFP-BMSCs transplantation will be a potential treatment for AD.     

Atrophy/hypertrophy cell signaling in muscles of young athletes trained with vibrational-proprioceptive stimulation

Abstract

Objective: To compare the effects of isokinetic (ISO-K) and vibrational-proprioceptive (VIB) trainings on muscle mass and strength.

Methods: In 29 ISO-K- or VIB-trained young athletes we evaluated: force, muscle fiber morphometry, and gene expression of muscle atrophy/hypertrophy cell signaling.

Results: VIB training increased the maximal isometric unilateral leg extension force by 48·1%. ISO-K training improved the force by 24·8%. Both improvements were statistically significant (P0·01). The more functional effectiveness of the VIB training in comparison with the ISO-K training was shown by the statistical significance changes only in VIB group in: rate of force development in time segment 0-50 ms (P<0·001), squat jump (P<0·05) and 30-m acceleration running test (P<0·05). VIB training induced a highly significant increase of mean diameter of fast fiber (+9%, P<0·001), but not of slow muscle fibers (?3%, not significant). No neural cell adhesion molecule-positive (N-CAM⁺) and embryonic myosin heavy chain-positive (MHC-emb⁺) myofibers were detected. VIB induced a significant twofold increase (P<0·05) of the skeletal muscle isoform insulin-like growth factor-1 (IGF-1) Ec mRNA. Atrogin-1 and muscle ring finger-1 (MuRF-1) did not change, but myostatin was strongly downregulated after VIB training (P<0·001). Peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) expression increased in post-training groups, but only in VIB reached statistical significance (+228%, P<0·05).

Discussion: We demonstrated that both trainings are effective and do not induce muscle damage. Only VIB-trained group showed statistical significance increase of hypertrophy cell signaling pathways (IGF-1Ec and PGC-1α upregulation, and myostatin downregulation) leading to hypertrophy of fast twitch muscle fibers.     

体外培养条件下人骨髓间充质干细胞碱性成纤维细胞生长因子基因的转染与鉴定

背景：骨髓间充质干细胞的定向分化需要合适生长因子的调控,利用细胞因子基因转染促进其生长、定向分化和加速骨缺损修复是近年来研究热点。 目的：探讨在体外培养条件下转染碱性成纤维细胞生长因子基因对人骨髓间充质干细胞生物学特性的影响。 方法：将含人pcDNA3.1-bFGF真核表达载体DH-5α菌扩增,用EndoFree质粒抽提纯化试剂盒抽提质粒,并对所提取的pcDNA3.1-bFGF重组表达质粒进行酶切鉴定和测序。利用脂质体将pcDNA3.1-bFGF质粒转染到生长良好的P3代骨髓间充质干细胞,G418筛选获得抗性克隆。采用荧光定量PCR、免疫组化、免疫荧光、Western-blot检测转染后骨髓间充质干细胞碱性成纤维细胞生长因子基因及其产物的表达,流式细胞仪检测细胞增殖周期。 结果与结论：脂质体介导pcDNA3.1-bFGF重组表达质粒转染骨髓间充质干细胞后,转染细胞确实表达碱性成纤维细胞生长因子,且表达部位主要位于胞浆。转染细胞增殖活力加强,处于增殖周期的细胞比例更高(P < 0.05)。提示采用脂质体转染法能将pcDNA3.1-bFGF成功导入体外培养的骨髓间充质干细胞,碱性成纤维细胞生长因子基因转染后可改善骨髓间充质干细胞的生存状态,促进其增殖。     

Vertebral artery dominance,brainstem auditory evoked potential,and vertigo of vascular origin

Abstract

Objective: Vertebral artery dominance (VAD) is defined when there is a significant difference between the diameters of the vertebral arteries (VAs). VAD may be a risk factor for vertigo of vascular origin. The objectives of this study were: (1) to investigate changes of brainstem auditory evoked potential (BAEP) in patients with vertigo caused by VAD through magnetic resonance; and (2) to understand the possible mechanism(s) by which VAD triggers vertigo of vascular origin.

Methods: This prospective study involved 64 patients with vertigo, including 35 patients with VAD (VAD group) and 29 without VAD (non-VAD group) as detected by head magnetic resonance angiography. Age, sex, and other clinical histories were comparable in both groups. The degree of vertigo was graded and BAEP examination was performed in each patient. BAEP changes as well as their correlations of BAEP with the dominant VA and basilar artery (BA) were analyzed in both groups.

Results: The rate of abnormal BA shapes was 60% in the VAD group compared with 34·5% in the non-VAD group (Chi-square?=?4·135, P<0·05). The median BA curvature was higher in the VAD group than that in the non-VAD group, 3·67 and 1·73 mm, respectively (P<0·01). Peak latencies (I, III, and V) in the VAD group were longer than those in the non-VAD group (P<0·01), but the difference in the III did not reach statistical significance (t?=?1·916, P>0·05). Interpeak latencies (III–V and I–V) were longer in the VAD group than those in the non-VAD group (P<0·05); there was no significant difference in the interpeak latencies of I–III (P>0·05). The III–V/I–III ratios were higher in the VAD group than those in the non-VAD group. The vertigo severity level was significantly higher in the VAD group than that in the non-VAD group (3·2±1·0 versus 2·2±0·7). The vertigo severity level correlated with VAD and every major anomaly index of BAEP; its correlations with III–V/I–III were remarkably significant (r?=?0·617, P?=?0·013).

Conclusion: The incidence of abnormal BA shapes and abnormal BAEP, and the vertigo severity level were higher in VAD patients. Moreover, VAD was found to correlate with abnormal BAEP, suggesting that VAD contributed to vertigo of vascular origin.     

Comparative study of 3D reconstruction of rat sciatic nerve microvessels using Evans blue and lead oxide

Abstract

Background:

The blood supply of peripheral nerve grafts is one of the important factors that affect nerve regeneration. Many investigators have studied how intraneural microvessels are distributed and ways to promote the angiogenesis of grafts. However, there still does not exist an ideal intraneural microvascular model. The purpose of this study was to compare the three-dimensional (3D) reconstruction of microvessels of the sciatic nerve in Sprague-Dawley (SD) rats after systemic perfusion with Evans blue (EB) or lead oxide.

Methods:

Ten adult SD rats were randomized to a fluorography group (EB) or radiography group (lead oxide). After administration of the perfusion agents, imaging information was obtained by fluorescence microscopy and micro-computed tomography (μCT). Three-dimensional reconstruction was performed, and the diameter of microvessels at a constant distance (a cross-section was taken every 1 mm), the vascular index, and volume were measured. Two-dimensional (2D) images were obtained by serial sectioning and μCT scanning using the two methods described.

Results:

In the EB group, the diameter, vascular area, and vascular index of microvessels were 11·79 ± 7·23 μm, 0.14 ± 0.05 mm², and 24·19 ± 5·03%, respectively, and in the lead oxide group 26·45 ± 11·81 μm, 0.06 ± 0.02 mm², and 10·73 ± 2·06%, respectively. Microvessels with diameters <20 μm were visualized better in the EB group than in the lead oxide group (P < 0·01). However, there was no significant difference between the groups in the visualization of microvessels with diameters 20–49 μm (P > 0·05).

Conclusions:

Both EB and lead oxide can be used for 2D study of intraneural microvessels and 3D observation after reconstruction. Lead oxide is easy to use, and though its resolution is lower than that of EB for smaller microvessels with diameters <20 μm, it is more suitable for studying a large sample volume.     

Electrophysiological profile of the patients with MuSK positive myasthenia gravis

Abstract

Objectives:

To determine the electrophysiological profile of our cohort of patients with muscle-specific tyrosine kinase (MuSK) positive myasthenia gravis (MG).

Methods:

Repetitive nerve stimulation test (RNS) and jitter analysis using concentric needle electrode were performed in 31 MuSK and in 28 acetylcholine receptor (AChR) positive MG patients.

Results:

Pathological RNS was verified in 16 (51·6%) MuSK and 26 (92·9%) AChR MG patients (P < 0·01). Pathological jitter analysis was registered in 28 (90·3%) MuSK and 26 (92·9%) AChR MG patients (P > 0·05). Increased jitter was present in extensor digitorum communis (EDC) in 23 (74·2%) MuSK and in 25 (89·3%) AChR MG patients (P > 0·05) as well as in orbicularis oculi (OO) muscle in 24 (85·7%) MuSK and 22 (81·5%) AChR MG patients (P > 0·05). Lower mean value of mean consecutive difference (MCD) and fewer potential pairs with increased jitter were registered in MuSK MG compared to AChR MG patients only in EDC muscle (P < 0·05). In MuSK MG patients, increased jitter was observed to be more frequent in patients with longer disease duration (P < 0·05) and also in those patients exhibiting more severe disease forms (P < 0·01) only in EDC muscle.

Discussion:

Repetitive nerve stimulation test has low sensitivity in MuSK MG patients, while jitter analysis shows high sensitivity, especially in facial muscles. The EDC muscle in MuSK MG patients usually shows increased jitter in more severe disease forms and later in the course of the disease.     

Cortical N-acetyl aspartate is a predictor of long-term clinical disability in multiple sclerosis

Abstract

Objective:

To evaluate the prognostic value of the cortical N-acetyl aspartate to creatine ratio (NAA/Cr) in early relapsing-remitting multiple sclerosis (RRMS).

Methods:

Sixteen patients with newly diagnosed RRMS were studied by serial MRI and MR spectroscopic imaging (MRSI) once every 6 months for 24 months. Clinical examinations, including the expanded disability status scale (EDSS), were performed at baseline, month 24, and at year 7.

Results:

Baseline cortical NAA/Cr correlated inversely with EDSS at month 24 (r = ?0·61, P < 0·05), and patients with EDSS ≧ 4 had a lower baseline cortical NAA/Cr compared to those with EDSS less than 4 (P < 0·05). Baseline cortical NAA/Cr also correlated inversely with EDSS at the 7-year follow-up (r = ?0·56, P < 0·05), and patients with EDSS ≧ 4 had a lower baseline cortical NAA/Cr compared to those with EDSS less than 4 (P < 0·05).

Baseline brain parenchymal fraction (BPF) correlated inversely with EDSS at month 24 (r = ?0·61, P < 0·05), but not with EDSS at year 7.

Discussion:

Cortical NAA/Cr in early RRMS correlated with clinical disability after 2 and 7 years and may be used as a predictor of long-term disease outcome.     

THR-18, a 18-mer peptide derived from PAI-1, is neuroprotective and improves thrombolysis by tPA in rat stroke models

Abstract

Objective: The thrombolytic treatment of stroke is limited by a narrow therapeutic time window and is associated with significant adverse side effects. To improve this situation, the modulation of tissue-type plasminogen activator (tPA) activity by a synthetic plasminogen activator inhibitor-1-derived 18-mer peptide (THR-18) was examined in two models of stroke in rats.

Methods: In the first model (thromboembolic), stroke was induced by intra-carotid injection of micro-clots to rats, and tPA (6 mg/kg) was intravenously infused for 30 minutes with or without THR-18 (1 mg/kg) at 4 hours post-induction. In the second model [transient middle cerebral artery occlusion (tMCAO)], stroke was induced for 2 hours by a transient mechanical occlusion. tPA and/or THR-18 (0·02, 0·1, and 1 mg/kg) were intravenously infused for 60 minutes at the time of reperfusion.

Results: In the thromboembolic model, cerebral blood flow, measured before and up to 5·5 hours post-induction, revealed that tPA administration caused reperfusion of flow at 30 minutes post-infusion. Later on, an additional increase in reperfusion was seen in the tPA+THR-18 group, and not with tPA alone. In both models, the frequency of intracranial hemorrhage in the tPA-treated group was found to be significantly higher than the control, and this tPA effect was attenuated by THR-18. In the thromboembolic study, infarct size and brain edema were similar in the control and tPA-treated rats. However, the combination of tPA and THR-18 caused a statistically significant reduction in both parameters (infarct size 17·8 versus 25·0%, brain edema 5 versus 8%, tPA+THR-18 versus control, respectively). In the tMCAO mechanical model, infarct size and brain edema were both increased by tPA treatment as compared to the control group, and this increase was markedly diminished by THR-18 co-administration. Neurobehavioral assessment of the tMCAO animals performed at 72 hours post-stroke induction revealed significant improvements (P<0·05-0·01) in neuroscores in all groups of animals treated with peptide-tPA, as compared to the tPA monotherapy group. A significant (P<0·05) improvement in the neurological outcome was also seen in the THR-18 monoterapy group, as compared to the control animals, thus demonstrating a clear neuroprotective effect by the peptide on its own.

Discussion: The results support the use of THR-18 together with tPA in the thrombolytic therapy of stroke, in order to achieve better patency, less tPA-induced damage, and possibly a widening of tPA therapeutic time window.     

CD40 ligand as a potential biomarker for atherosclerotic instability

Abstract

Objective: The signaling protein CD40 and its ligand, CD40L, are thought to contribute to atherosclerotic plaque formation and rupture. We sought to determine their utility as markers of cerebral atherosclerosis and neurological dysfunction.

Methods: We recruited 82 patients with acute cerebral infarction (ACI) and classified each as having large-artery atherosclerosis (LAA, 30), small-artery occlusion (36), or cardioaortic embolism (16). We also recruited 17 patients who had carotid artery stenosis (CAS) without stroke and 20 healthy individuals as controls. CD40L expression on peripheral blood monocytes (PBMCs) was detected by direct immunofluorescence with flow cytometry, and serum soluble CD40L (sCD40L) was measured by ELISA.

Results: CD40L expression on PBMCs was highest in the LAA group, followed by that in the CAS group (both P < 0·01 versus control). It was also higher in patients with atherosclerotic infarction than in those without atherosclerosis (P < 0·05). PBMC CD40L expression was sensitive and specific for detecting atherosclerosis and LAA cerebral infarction and was superior to serum C-reactive protein for predicting cerebral atherosclerosis (P < 0·01). Serum sCD40L was higher in patients with ACI than in healthy controls (P < 0·01) or patients with CAS (P < 0·01) and correlated with increased disability on three scales (all P < 0·01).

Conclusions: We conclude that patients with ACI have an upregulated CD40–CD40L system, which could be used as a clinical biomarker for assessing atherosclerotic instability and severity of neurological dysfunction.     

Correlation between serum IL-1beta levels and cerebral edema extent in a hypertensive intracerebral hemorrhage rat model

Abstract

Background: Interleukin-1beta (IL-1beta) is a pro-inflammatory cytokine that is increased following hypertensive intracerebral hemorrhage (ICH), potentially related to neural damage by cerebral edema.

Objective: To investigate the correlation between post-ICH serum IL-1beta and cerebral edema in a hypertensive rat model.

Methods: We used 30 successful ICH male spontaneously hypertensive rats (SHR) subjected to autologous blood infusion and displaying behavioral abnormalities (ICH group), and 30 sham-operated rats. Cerebral edema was assessed at 8, 16, 24, 48, 72, and 120 hours using dry and wet right hemisphere weighing, and serum IL-1beta levels were determined by enzyme-linked immunosorbent assay (ELISA). Nonlinear regression was performed between serum IL-1beta levels and cerebral edema extent at different time intervals after ICH.

Results: No significant difference was observed in preoperative blood pressure between the two groups. In ICH rats, behavioral abnormalities were observed at all time points except at 120 hours Intracerebral hemorrhage rats exhibited significantly increased serum IL-1beta levels between 16 and 72 hours, and increased cerebral edema between 24 and 72 hours (all P < 0·05 vs sham-operated rats), but no significant differences were found in the sham-operated group. Serum IL-1beta and cerebral edema in the ICH group returned to baseline by 120 hours Serum IL-1beta levels were positively correlated with cerebral edema (r = 0·906, P = 0·001).

Conclusion: Serum IL-1beta was related to cerebral edema extent in hypertensive ICH rats, which may eventually be useful as an indicator for progression of cerebral edema after ICH, and contributing to the choice of a treatment strategy.     

Long-term follow-up of intra-aneurysmal coil embolization for unruptured paraclinoid aneurysms

Abstract

Objectives: The selection of therapeutic modalities, including endovascular coil embolization and surgical clipping, for management of unruptured paraclinoid aneurysms, remains controversial. Detailed long-term outcome data for endovascular coil embolization of unruptured paraclinoid aneurysms are still lacking. Thus, we evaluated the safety and efficacy of coil embolization of unruptured paraclinoid aneurysms.

Methods: From January 1998 to July 2010, 138 patients underwent endovascular coiling for 140 unruptured paraclinoid aneurysms. Their medical records and radiologic images were reviewed retrospectively.

Results: Complications occurred in 5·7% of 140 procedures and the morbidity rate was 0·7%. Of the 140 unruptured paraclinoid aneurysms, a total of 111 aneurysms underwent follow-up imaging evaluation at 2 years or more, or showing reopening on imaging studies within 2 years (65·6±37·2 months). Multivariate analysis revealed two predictors for reopening of the aneurysms: a maximum diameter of aneurysms and a dome/neck ratio of aneurysms (P<0·05). Reopening rates of aneurysms with maximum sizes of <8, 8–10, and >10 mm were 1%, 25%, and 75%, respectively. Reopening rates were significantly different among the three groups (P<0·05). In aneurysms with a maximum diameter of 8–10 mm, there was a significant difference of dome/neck ratios between the presence and absence of reopened aneurysms (P<0·05).

Discussion: The results indicate that endovascular coil embolization is a safe and effective treatment modality in selected patients with unruptured paraclinoid aneurysms. Consideration of the aneurysm size and the dome/neck ratio could assist in the selection of therapeutic modalities for these aneurysms.     

Dynamic cross-sectional changes of the middle cerebral artery in atherosclerotic stenosis detected by 3·0-Tesla MRI

Abstract

Objectives:

Atherosclerotic stenosis of the middle cerebral artery (MCA) is one of the causes of ischemic stroke, but aside from investigations using magnetic resonance angiography (MRA), studies evaluating stenosis are rare. The purpose of this study was to assess dynamic changes of MCA cross section between the systolic and diastolic phases in patients with cerebral infarction using 3·0-Tesla magnetic resonance imaging (3T MRI).

Methods:

We assessed 12 stroke patients with M1 stenosis in the MCA and 12 healthy volunteers. We measured MCA cross sections (proximal/distal to stenosis and on the stenosis) in the systolic and diastolic phases by synchronizing imaging with heartbeats, as well as the maximum flow velocity by using cine-phase contrast (PC) MRI. Each patient also underwent conventional MRA.

Results:

Differences in cross sections between systolic and diastolic phases were significantly smaller in the stenosed artery compared to the distal (P < 0·05) and proximal areas (P < 0·01) in stroke patients. The difference in maximal blood velocity between systolic and diastolic phases at the M1 stenosis was significantly larger than that in the area proximal to the stenosis (P < 0·05).

Discussion:

We clearly demonstrated dynamic cross-sectional changes in the stenotic areas by 3T MRI, suggesting hemodynamic shear stress, which may further enhance MCA atherosclerosis.     

Inhibitor effect of dexketoprofen in rat model of pentylenetetrazol-induced seizures

Objectives: The relationship between epilepsy and inflammation is known, and it has been reported that there is an increase in cyclooxygenase (COX) levels in epilepsy. We aim to reveal the anticonvulsant effects of dexketoprofen in pentylenetetrazol (PTZ)-induced seizures in rats.

Materials and Methods: Forty-eight male Sprague-Dawley rats, 24 of them for EEG recording and 24 of them are for behavioral studies, were randomly divided in two groups: Group A for EEG recordings and Group B for behavioral assessment. A weight of 70 mg/kg PTZ was used for behavioral studies after dexketoprofen administration. Thirty-five milligrams per kilogram PTZ were used for EEG recording after dexketoprofen administration. The electrodes were implanted on dura over the left frontal cortex and the reference electrode was implanted over the cerebellum for EEG recording. The Racine convulsion scale (RCS), first myoclonic jerk (FMJ) onset time, and spike percentages were evaluated between the two groups.

Results: There was a significant (P< 0·05) difference between the RCS, FMJ onset time (P< 0·001), and spike percentage (P< 0·05) between the groups (Group 2 compared with Groups 3 and 4).

Conclusion: Dexketoprofen has an antiepileptic feature and this effect increases as the dosage increases, however it is currently unknown through which mechanism this drug shows its anticonvulsant effect. Dexketoprofen, in the group of NSAIDs, shows an anticonvulsant effect on PTZ-induced epilepsy model. This study suggests that dexketoprofen can preferably be used with NSAIDs for epileptic patients in clinical practice.     

Comparison of the effect of aspirin and amantadine for the treatment of fatigue in multiple sclerosis: a randomized,blinded, crossover study

Abstract

Objectives: The purpose of this study was to compare the relative efficacy of acetylsalicylic acid (ASA) and amantadine for the treatment of fatigue in multiple sclerosis (MS).

Methods: A 10-week, randomized double-blind crossover clinical trial conducted from October 2009 to September 2010. Fifty-two patients with MS presenting fatigue at 21 to 53 years of age were randomly allocated to the two treatment groups. The first group received amantadine (100 mg twice daily) for a total of 4 weeks. The second group received ASA (500 mg once daily) for four weeks. After a 2-week washout period, they crossed over to the alternative treatment for 4 weeks. Patients were rated at baseline and the end of each phase with the Fatigue Severity Scale (FSS).

Results: ASA appeared to be equivalent in efficacy and safety to amantadine. A significant decrease in FSS occurred in both groups. Of the 26 patients treated with amantadine, the mean (SD) of FSS decreased from 4·8 (1·4) to 4·0 (1·4) (P<0·001). In the 26 patients treated with ASA, the mean (SD) of FSS decreased from 4·6 (1·4) to 3·5 (1·5) (P<0·001).

Discussion: This study demonstrates that both ASA and amantadine significantly reduce MS-related fatigue. Both ASA and amantadine have previously been shown to reduce fatigue, and we postulate that treatment with ASA and amantadine may have similar benefits.     

Safety and therapeutic efficacy of the second treatment for new fractures developed after initial vertebroplasty performed for painful vertebral compression fractures

Abstract

Objectives: There is no report on the safety and therapeutic efficacy of the second treatment for new vertebral fractures developed after vertebroplasty. This study aims to examine the therapeutic effects and clinical characteristics in patients undergoing a second vertebroplasty for these new fractures.

Methods: The initial treatment group included 182 patients (276 vertebrae) who underwent vertebroplasty. Among 182 patients, the second treatment group included 34 patients (36 vertebrae) who developed new fractures postoperatively, which were retreated. Analgesic effects on the day following surgery, frequency of new fractures during the 12 month period after surgery, and other clinical characteristics were compared between the initial and second treatment groups. Furthermore, similar comparisons were performed between patients with adjacent and non-adjacent vertebral fractures in the second treatment group.

Results: The improvement rates in visual analogue scale (VAS) scores before and after surgery were 83·4% in the initial treatment group and 85·6% in the second treatment group (P = 0·27). The frequencies of new fractures occurring within 12 months after surgery were 20·9% and 20·6%, respectively.

Within the second treatment group, the VAS improvement rates were 76·7% in the adjacent and 88·2% in the non-adjacent vertebral fracture groups (P = 0·83). However, the frequencies of subsequent new fractures after the second treatment were 31·6% and 5·9%, respectively, being significantly higher in the adjacent vertebral fracture group (P < 0·05).

Conclusions: Additional vertebroplasty for new fractures exerts analgesic effects similar to those of the initial procedure. However, we must note that the second treatment for new adjacent vertebral fractures frequently causes more subsequent new fractures in comparison with non-adjacent fractures.     

Poor outcome prediction by burst suppression ratio in adults with post-anoxic coma without hypothermia

Abstract

Purpose:

Burst suppression ratio (BSR) is a quantitative electroencephalography (qEEG) parameter. The purpose of our study was to compare the accuracy of BSR when compared to other EEG parameters in predicting poor outcomes in adults who sustained post-anoxic coma while not being subjected to therapeutic hypothermia.

Methods:

EEG was registered and recorded at least once within 7 days of post-anoxic coma onset. Electrodes were placed according to the international 10–20 system, using a 16-channel layout. Each EEG expert scored raw EEG using a grading scale adapted from Young and scored amplitude-integrated electroencephalography tracings, in addition to obtaining qEEG parameters defined as BSR with a defined threshold. Glasgow outcome scales of 1 and 2 at 3 months, determined by two blinded neurologists, were defined as poor outcome.

Results:

Sixty patients with Glasgow coma scale score of 8 or less after anoxic accident were included. The sensitivity (97·1%), specificity (73·3%), positive predictive value (82·5%), and negative prediction value (95·0%) of BSR in predicting poor outcome were higher than other EEG variables. BSR1 and BSR2 were reliable in predicting death (area under the curve > 0·8, P < 0·05), with the respective cutoff points being 39·8% and 61·6%. BSR1 was reliable in predicting poor outcome (area under the curve = 0·820, P < 0·05) with a cutoff point of 23·9%. BSR1 was also an independent predictor of increased risk of death (odds ratio = 1·042, 95% confidence intervals: 1·012–1·073, P = 0·006).

Discussion:

BSR may be a better predictor in prognosticating poor outcomes in patients with post-anoxic coma who do not undergo therapeutic hypothermia when compared to other qEEG parameters.     

Erythropoietin reduces white matter damage in two-day-old rats exposed to hypoxic/ischemia injury

Objective: The aim of the study was to investigate whether erythropoietin (EPO) could protect against white matter damage (WMD) in a preterm equivalent neonatal rat hypoxic-ischemia (HI) model.

Methods: 113 two-day-old male rat pups were divided randomly into three groups: sham-treated, bilateral carotid artery occlusion (BCAO)-treated, BCAO + EPO-treated group. EPO (50 U/10 g body weight) or saline alone was administered intraperitoneally immediately after BCAO surgery. Body weight, brain weight, brain water content, and expression of myelin basic protein (MBP) were assessed at day 1, 3, 7, and 14 after HI insult. Morris water-maze (MWM) test was used to assess neurological behavior from day 31 to 35 after HI insult.

Results: Body weights of BCAO + EPO group were greater than those of BCAO group rats (P < 0.05). Specifically, at day 3 and 7 after HI, brain weights of BCAO + EPO-treated rats were higher than BCAO-treated animals (P < 0.05); at day 7 and 14 after HI, MBP of BCAO + EPO-treated rats were higher than BCAO-treated animals (P < 0.05). Similarly, the brain water content at day 3 after HI in BCAO + EPO-treated rats was lower than BCAO-treated animals (P < 0.05). The body weight, brain weight, brain water content, and MBP expression in BCAO + EPO-treated group were comparable to those in the sham-treated group. Spatial learning and memory of BCAO + EPO-treated rats was significantly improved over the BCAO-treated group and was comparable to the sham-operated animals.

Conclusion: EPO treatment could be a potential intervention in treating WMD for preterm infants.     

Increased fasting glucose and the prevalence of arterial stiffness: a cross-sectional study in Chinese adults

Abstract

Objective:

Previous studies have shown that diabetes increases the prevalence of arterial stiffness. However, it remains controversial whether impaired fasting glucose (IFG), a key pre-diabetes condition, is associated with increased risk of arterial stiffness. This study aimed to investigate the relationship between increased fasting plasma glucose (FPG) and the prevalence of arterial stiffness in a Chinese adult population.

Methods:

A random sample of 5039 participants aged 40 years or older (40·0% female) were enrolled in this study. Information on potential risk factors for cardiovascular disease was collected, and the presence of arterial stiffness was assessed by measuring brachial-ankle pulse wave velocity (baPWV). Participants were stratified into three groups: normal fasting glucose (NFG), IFG, and diabetes mellitus (DM). The IFG group was further stratified by quartiles based on the level of FPG into Q1, Q2, Q3, and Q4.

Results:

Fasting plasma glucose level was found to be independently and positively associated with baPWV. The adjusted odds ratios (ORs) (95% confidence interval (CI)) for arterial stiffness were 1·09 (0·80–1·48), 1·33 (0·98–1·81), 1·27 (0·93–1·73), 1·82 (1·31–2·53), and 2·15 (1·66–2·79) for those in IFG Q1, Q2, Q3, Q4, and DM groups compared with NFG group (P < 0·001), respectively, after adjusting for age, sex, and other potential confounders. Moreover, male participants and participants younger than 60 years were closely associated with the presence and severity of arterial stiffness (P < 0·001).

Conclusion:

Our study reports a previously unidentified positive association between increased FPG and the prevalence of arterial stiffness, suggesting the importance of FPG control in the prevention of arterial stiffness.     

A simple clinical and MRI scale to predict good outcome in t-PA patients

Abstract

Background and purpose: The frequency of good outcome at 3 months after tissue plasminogen activator (t-PA) therapy is ～35%. The present study aimed to devise a simple scale to predict good outcome using clinical factors and magnetic resonance imaging (MRI) findings before and immediately after t-PA infusion.

Methods: Consecutive patients with acute ischemic stroke treated with t-PA within 3 hours of stroke onset were studied prospectively. We assessed clinical factors independently associated with good outcome [modified Rankin scale (mRS): 0-1] at 3 months after t-PA therapy. We created a simple scale to predict good outcome in t-PA patients using factors selected by multivariate logistic regression analysis.

Results: Subjects comprised 105 patients (69 men; median age, 74 years). Multivariate logistic regression analysis revealed the following independent factors associated with good outcome: baseline National Institutes of Health Stroke Scale (NIHSS) <11 [odds ratio (OR), 13·64; 95% confidence interval (CI), 3·588-51·822; P = 0·0001], glucose <150 mg/dl (OR, 3·76; 95%CI, 1·014-13·963; P = 0·0475), and early recanalization within 1 hour after t-PA infusion (OR, 5·28; 95%CI, 1·179-23·656; P = 0·0296). Those three variables were selected for use in the good outcome scale, with NIHSS <11 as 2 points, glucose <150 mg/dl as 1 point, and early recanalization as 1 point. Frequencies of patients with good outcome for each score were as follows: score 0, 0·0%; score 1, 7·1%; score 2, 43·5%; score 3, 65·4%; and score 4, 71·4%. The C statistic for the score was 0·849 (95%CI, 0·776-0·922).

Conclusion: A simple clinical and MRI scale can predict good outcome in t-PA patients.