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Using a new method for measuring the molecular ratio (R) of inhalation to exhalation, we investigated the effect of high fraction of inspired oxygen (FIO2) on oxygen consumption (VO2), carbon dioxide generation (VCO2), and respiratory quotient (RQ) in mechanically ventilated rats. Twelve rats were equally assigned into two groups by anesthetics: intravenous midazolam/fentanyl vs. inhaled isoflurane. R, VO2, VCO2, and RQ were measured at FIO2 0.3 or 1.0. R error was ± 0.003. R was 1.0099 ± 0.0023 with isoflurane and 1.0074 ± 0.0018 with midazolam/fentanyl. R was 1.0081 ± 0.0017 at an FIO2 of 0.3 and 1.0092 ± 0.0029 at an FIO2 of 1.0. There were no differences in VCO2 among the groups. VO2 increased at FIO2 1.0, which was more notable when midazolam/fentanyl was used (isoflurane-FIO2 0.3: 15.4 ± 1.1; isoflurane-FIO2 1.0: 17.2 ± 1.8; midazolam/fentanyl-FIO2 0.3: 15.4 ± 1.1; midazolam/fentanyl-FIO2 1.0: 21.0 ± 2.2 mL/kg/min at STP). The RQ was lower at FIO2 1.0 than FIO2 0.3 (isoflurane-FIO2 0.3: 0.80 ± 0.07; isoflurane-FIO2 1.0: 0.71 ± 0.05; midazolam/fentanyl-FIO2 0.3: 0.79 ± 0.03; midazolam/fentanyl-FIO2 1.0: 0.59 ± 0.04). R was not affected by either anesthetics or FIO2. Inspired 100% O2 increased VO2 and decreased RQ, which might be more remarkable when midazolam/fentanyl was used. [ABSTRACT FROM AUTHOR]

The pituitary gland plays an important endocrinal role, however its damage after cardiac arrest (CA) has not been well elucidated. The aim of this study was to determine a pituitary gland damage induced by CA. Rats were subjected to 10-min asphyxia and cardiopulmonary resuscitation (CPR). Immunohistochemistry and ELISA assays were used to evaluate the pituitary damage and endocrine function. Samples were collected at pre-CA, and 30 and 120 min after cardio pulmonary resuscitation. Triphenyltetrazolium chloride (TTC) staining demonstrated the expansion of the pituitary damage over time. There was phenotypic validity between the pars distalis and nervosa. Both CT-proAVP (pars nervosa hormone) and GH/IGF-1 (pars distalis hormone) decreased over time, and a different expression pattern corresponding to the damaged areas was noted (CT-proAVP, 30.2 ± 6.2, 31.5 ± 5.9, and 16.3 ± 7.6 pg/mg protein, p < 0.01; GH/IGF-1, 2.63 ± 0.61, 0.62 ± 0.36, and 2.01 ± 0.41 ng/mg protein, p < 0.01 respectively). Similarly, the expression pattern between these hormones in the end-organ systems showed phenotypic validity. Plasma CT-proAVP (r = 0.771, p = 0.025) and IGF-1 (r = −0.775, p = 0.024) demonstrated a strong correlation with TTC staining area. Our data suggested that CA induces pathological and functional damage to the pituitary gland. [ABSTRACT FROM AUTHOR]

A subset of patients with chronic subdural hematoma (CSDH) remains refractory to standard treatment with hematoma drainage by burr-hole craniotomy and irrigation. We recently reported the usefulness of middle meningeal artery (MMA) embolization for intractable CSDH in patients with multiple intractable risk factors. We present the midterm outcomes of MMA embolization in patients with intractable CSDHs. Seventeen consecutive patients (average age, 76.4 years; 12 men [71%]) underwent MMA embolization of CSDH from January 2014 to July 2017. Earlier interventions included embolization using N -butyl-2-cyanoacrylate (although trisacryl gelatin microspheres were used in recent cases), followed by burr-hole craniotomy and irrigation in all cases. None of the patients experienced perioperative complications or postoperative recurrence. The modified Rankin Scale scores, which were unfavorable at admission, improved significantly at discharge but were comparable to those at the time of hospitalization when measured during the follow-up period. Although the patients required rehospitalization at other departments for unrelated causes, none required rehospitalization in our department. Despite the known unfavorable outcomes of patients with intractable CSDHs, MMA embolization was not associated with recurrent CSDH or rehospitalization in our department in the current case series. MMA embolization should be considered a preferred therapeutic option for intractable CSDHs. [ABSTRACT FROM AUTHOR]

Background High mobility group box 1 (HMGB1) protein plays a key role in triggering inflammatory responses in many diseases. Our previous study showed that HMGB1 is found upstream of secondary damage in traumatic brain injury (TBI). We found that anti-HMGB1 monoclonal antibody (mAb) effectively decreased acute brain damage, including the disruption of the blood-brain barrier, brain edema, and neurologic dysfunction. This effect of anti-HMGB1 mAb lasts for at least 1 week. In this study, we explored subacute effects of anti-HMGB1 mAb after TBI. Methods TBI was induced in rats by fluid percussion. Anti-HMGB1 mAb or control mAb was given intravenously after TBI. Histochemical staining, plasma levels of HMGB1, motor activity and memory, and video electroencephalography monitoring were evaluated 2 weeks after fluid percussion injury. Results Anti-HMGB1 mAb remarkably attenuated accumulation of activated microglia in the rat cortex in the ipsilateral hemisphere after TBI. Anti-HMGB1 mAb also prevented neuronal death in the hippocampus in the ipsilateral hemisphere after TBI. Treatment of rats with anti-HMGB1 mAb inhibited HMGB1 translocation and suppressed impairment of motor function. The beneficial effects of anti-HMGB1 mAb on motor and cognitive function persisted for 14 days after injury. Treatment with anti-HMGB1 mAb also had positive effects on electroencephalography activity. Conclusions The beneficial effects of anti-HMGB1 mAb continued during the subacute postinjury phase, suggesting that anti-HMGB1 mAb may prevent cognitive dysfunction after TBI. [ABSTRACT FROM AUTHOR]

Highlights: [•] We hypothesized that glycerol or mannitol might enhance the therapeutic benefits of cell transplantation in a rat TBI model. [•] Compared to PBS or glycerol, the administration of mannitol resulted in increased BBB disruption. [•] More MSCs were observed in the injured brain tissues of mannitol-treated rats than in glycerol or PBS-treated rats at 24h after transplantation. [•] Intra-arterial transplantation of MSCs combined with mannitol is an effective treatment in a TBI model of rats. [ABSTRACT FROM AUTHOR]

Objective: High mobility group box-1 (HMGB1) plays an important role in triggering inflammatory responses in many types of diseases. In this study, we examined the involvement of HMGB1 in traumatic brain injury (TBI) and evaluated the ability of intravenously administered neutralizing anti-HMGB1 monoclonal antibody (mAb) to attenuate brain injury. Methods: Traumatic brain injury was induced in rats or mice by fluid percussion. Anti-HMGB1 mAb or control mAb was administered intravenously after TBI. Results: Anti-HMGB1 mAb remarkably inhibited fluid percussion-induced brain edema in rats, as detected by T2-weighted magnetic resonance imaging; this was associated with inhibition of HMGB1 translocation, protection of blood-brain barrier (BBB) integrity, suppression of inflammatory molecule expression, and improvement of motor function. In contrast, intravenous injection of recombinant HMGB1 dose-dependently produced the opposite effects. Experiments using receptor for advanced glycation end product (RAGE)−/−, toll-like receptor-4 (TLR4)−/−, and TLR2−/− mice suggested the involvement of RAGE as the predominant receptor for HMGB1. Interpretation: Anti-HMGB1 mAb may provide a novel and effective therapy for TBI by protecting against BBB disruption and reducing the inflammatory responses induced by HMGB1. ANN NEUROL 2012;72:373-384 [ABSTRACT FROM AUTHOR]

Background: High-quality cardiopulmonary resuscitation (HQ-CPR) is of paramount importance to improve neurological outcomes of cardiac arrest (CA). The purpose of this study was to evaluate chest compression methods by combining two theories: cardiac and thoracic pumps. Methods: Male Sprague-Dawley rats were used. Three types of chest compression methods were studied. The 1-side method was performed vertically with 2 fingers over the sternum. The 2-side method was performed horizontally with 2 fingers, bilaterally squeezing the chest wall. The 3-side method combined the 1-side and the 2-side methods. Rats underwent 10 min of asphyxial CA. We examined ROSC rates, the left ventricular functions, several arterial pressures, intrathoracic pressure, and brain tissue oxygen. Results: The 3-side group achieved 100% return of spontaneous circulation (ROSC) from asphyxial CA, while the 1-side group and 2-side group achieved 80% and 60% ROSC, respectively. Three-side chest compression significantly shortened the time for ROSC among the groups (1-side, 105 ± 36.0; 2-side, 141 ± 21.7; 3-side, 57.8 ± 12.3 s, respectively, P < 0.05). Three-side significantly increased the intrathoracic pressure (esophagus, 7.6 ± 1.9, 7.3 ± 2.8, vs. 12.7 ± 2.2; mmHg, P < 0.01), the cardiac stroke volume (the ratio of the baseline 1.2 ± 0.6, 1.3 ± 0.1, vs. 2.1 ± 0.6, P < 0.05), and the common carotid arterial pressure (subtracted by femoral arterial pressure 4.0 ± 2.5, 0.3 ± 1.6, vs. 8.4 ± 2.6; mmHg, P < 0.01). Three-side significantly increased the brain tissue oxygen (the ratio of baseline 1.4±0.1, 1.3±0.2, vs. 1.6 ± 0.04, P < 0.05). Conclusions: These results suggest that increased intrathoracic pressure by 3-side CPR improves the cardiac output, which may in turn help brain oxygenation during CPR. [ABSTRACT FROM AUTHOR]

Cardiac arrest (CA) patients suffer from systemic ischemia–reperfusion (IR) injury leading to multiple organ failure; however, few studies have focused on tissue-specific pathophysiological responses to IR-induced oxidative stress. Herein, we investigated biological and physiological parameters of the brain and heart, and we particularly focused on the lung dysfunction that has not been well studied to date. We aimed to understand tissue-specific susceptibility to oxidative stress and tested how oxygen concentrations in the post-resuscitation setting would affect outcomes. Rats were resuscitated from 10 min of asphyxia CA. Mechanical ventilation was initiated at the beginning of cardiopulmonary resuscitation. We examined animals with or without CA, and those were further divided into the animals exposed to 100% oxygen (CA_Hypero) or those with 30% oxygen (CA_Normo) for 2 h after resuscitation. Biological and physiological parameters of the brain, heart, and lungs were assessed. The brain and lung functions were decreased after CA and resuscitation indicated by worse modified neurological score as compared to baseline (222 ± 33 vs. 500 ± 0, P < 0.05), and decreased PaO2 (20 min after resuscitation: 113 ± 9 vs. baseline: 128 ± 9 mmHg, P < 0.05) and increased airway pressure (2 h: 10.3 ± 0.3 vs. baseline: 8.1 ± 0.2 mmHg, P < 0.001), whereas the heart function measured by echocardiography did not show significant differences compared before and after CA (ejection fraction, 24 h: 77.9 ± 3.3% vs. baseline: 82.2 ± 1.9%, P = 0.2886; fractional shortening, 24 h: 42.9 ± 3.1% vs. baseline: 45.7 ± 1.9%, P = 0.4658). Likewise, increases of superoxide production in the brain and lungs were remarkable, while those in the heart were moderate. mRNA gene expression analysis revealed that CA_Hypero group had increases in Il1b as compared to CA_Normo group significantly in the brain (P < 0.01) and lungs (P < 0.001) but not the heart (P = 0.4848). Similarly, hyperoxia-induced increases in other inflammatory and apoptotic mRNA gene expression were observed in the brain, whereas no differences were found in the heart. Upon systemic IR injury initiated by asphyxia CA, hyperoxia-induced injury exacerbated inflammation/apoptosis signals in the brain and lungs but might not affect the heart. Hyperoxia following asphyxia CA is more damaging to the brain and lungs but not the heart. [ABSTRACT FROM AUTHOR]

Objectives: Cardiac arrest and subsequent resuscitation have been shown to deplete plasma phospholipids. This depletion of phospholipids in circulating plasma may contribute to organ damage postresuscitation. Our aim was to identify the diminishment of essential phospholipids in postresuscitation plasma and develop a novel therapeutic approach of supplementing these depleted phospholipids that are required to prevent organ dysfunction postcardiac arrest, which may lead to improved survival.Design: Clinical case control study followed by translational laboratory study.Setting: Research institution.Patients/subjects: Adult cardiac arrest patients and male Sprague-Dawley rats.Interventions: Resuscitated rats after 10-minute asphyxial cardiac arrest were randomized to be treated with lysophosphatidylcholine specie or vehicle.Measurements and Main Results: We first performed a phospholipid survey on human cardiac arrest and control plasma. Using mass spectrometry analysis followed by multivariable regression analyses, we found that plasma lysophosphatidylcholine levels were an independent discriminator of cardiac arrest. We also found that decreased plasma lysophosphatidylcholine was associated with poor patient outcomes. A similar association was observed in our rat model, with significantly greater depletion of plasma lysophosphatidylcholine with increased cardiac arrest time, suggesting an association of lysophosphatidylcholine levels with injury severity. Using a 10-minute cardiac arrest rat model, we tested supplementation of depleted lysophosphatidylcholine species, lysophosphatidylcholine(18:1), and lysophosphatidylcholine(22:6), which resulted in significantly increased survival compared with control. Furthermore, the survived rats treated with these lysophosphatidylcholine species exhibited significantly improved brain function. However, supplementing lysophosphatidylcholine(18:0), which did not decrease in the plasma after 10-minute cardiac arrest, had no beneficial effect.Conclusions: Our data suggest that decreased plasma lysophosphatidylcholine is a major contributor to mortality and brain damage postcardiac arrest, and its supplementation may be a novel therapeutic approach. [ABSTRACT FROM AUTHOR]

Introduction: Although self-expanding carotid stents may dilate gradually, the degrees of residual stenosis have been quantified by the NASCET criteria, which is too simple to reflect the configuration of the stented artery. We measured the volumes of the stent lumens chronologically by 3D-CT in patients after carotid artery stenting (CAS), and analyzed the correlations between the volume change and medical factors. Methods: Fourteen patients with carotid artery stenosis were treated using self-expanding, open-cell stents. All patients underwent preoperative plaque MRI (magnetization-prepared rapid acquisition gradient-echo, MPRAGE) and chronological 3D-CT examinations of their stents immediately after their placement and 1 day, 1 week, and 1 month after the procedure. The volume of the stent lumen was measured using a 3D workstation. The correlations between stent volume and various factors including the presence of underlying diseases, plaque characteristics, and the results of the CAS procedure were analyzed. Results: Stent volume gradually increased in each case and had increased by 1.04-1.55 (mean, 1.25)-fold at 1 postoperative month. The presence of underlying medical diseases, plaque length, the degree of residual stenosis immediately after CAS, and plaque calcification did not have an impact on the change in stent volume. On the other hand, the stent volume increase was significantly larger in the patients with vulnerable plaques that demonstrated high MPRAGE signal intensity ( P < 0.05). Conclusions: A 3D-CT examination is useful for precisely measuring stent volume. Self-expanding stents in carotid arteries containing vulnerable plaques expand significantly more than those without such plaques in a follow-up period. [ABSTRACT FROM AUTHOR]

Epilepsy is a chronic neurological disorder, which presents with various forms of seizures. Traditional treatments, including medication using antiepileptic drugs, remain the treatment of choice for epilepsy. Recent development in surgical techniques and approaches has improved treatment outcomes. However, several epileptic patients still suffer from intractable seizures despite the advent of the multimodality of therapies. In this article, we initially provide an overview of clinical presentation of epilepsy then describe clinically relevant animal models of epilepsy. Subsequently, we discuss the concepts of regenerative medicine including cell therapy, neuroprotective agents, and electrical stimulation, which are reviewed within the context of our data. [ABSTRACT FROM AUTHOR]