Transient forebrain ischemia under hyperthermic condition accelerates memory impairment and neuronal death in the gerbil hippocampus by increasing NMDAR1 expression.

Altered expression levels of N­methyl­D­aspartate receptor (NMDAR), a ligand­gated ion channel, have a harmful effect on cellular survival. Hyperthermia is a proven risk factor of transient forebrain ischemia (tFI) and can cause extensive and severe brain damage associated with mortality. The objective of the present study was to investigate whether hyperthermic preconditioning affected NMDAR1 immunoreactivity associated with deterioration of neuronal function in the gerbil hippocampal CA1 region following tFI via histological and western blot analyses. Hyperthermic preconditioning was performed for 1 h before tFI, which was developed by ligating common carotid arteries for 5 min. tFI­induced cognitive impairment under hyperthermia was worse compared with that under normothermia. Loss (death) of pyramidal neurons in the CA1 region occurred fast and was more severe under hyperthermia compared with that under normothermia. NMDAR1 immunoreactivity was not observed in the somata of pyramidal neurons of sham gerbils with normothermia. However, its immunoreactivity was strong in the somata and processes at 12 h post­tFI. Thereafter, NMDAR1 immunoreactivity decreased with time after tFI. On the other hand, NMDAR1 immunoreactivity under hyperthermia was significantly increased in the somata and processes at 6 h post­tFI. The change pattern of NMDAR1 immunoreactivity under hyperthermia was different from that under normothermia. Overall, accelerated tFI­induced neuronal death under hyperthermia may be closely associated with altered NMDAR1 expression compared with that under normothermia.

Neuronal Death in the CNS Autonomic Control Center Comes Very Early after Cardiac Arrest and Is Not Significantly Attenuated by Prompt Hypothermic Treatment in Rats.

Autonomic dysfunction in the central nervous system (CNS) can cause death after recovery from a cardiac arrest (CA). However, few studies on histopathological changes in animal models of CA have been reported. In this study, we investigated the prevalence of neuronal death and damage in various brain regions and the spinal cord at early times after asphyxial CA and we studied the relationship between the mortality rate and neuronal damage following hypothermic treatment after CA. Rats were subjected to 7-8 min of asphyxial CA, followed by resuscitation and prompt hypothermic treatment. Eight regions related to autonomic control (the cingulate cortex, hippocampus, thalamus, hypothalamus, myelencephalon, and spinal cord) were examined using cresyl violet (a marker for Nissl substance) and Fluoro-Jade B (a marker for neuronal death). The survival rate was 44.5% 1 day post-CA, 18.2% 2 days post-CA and 0% 5 days post-CA. Neuronal death started 12 h post-CA in the gigantocellular reticular nucleus and caudoventrolateral reticular nucleus in the myelencephalon and lamina VII in the cervical, thoracic, lumbar, and sacral spinal cord, of which neurons are related to autonomic lower motor neurons. In these regions, Iba-1 immunoreactivity indicating microglial activation (microgliosis) was gradually increased with time after CA. Prompt hypothermic treatment increased the survival rate at 5 days after CA with an attenuation of neuronal damages and death in the damaged regions. However, the survival rate was 0% at 12 days after CA. Taken together, our study suggests that the early damage and death of neurons related to autonomic lower motor neurons was significantly related to the high mortality rate after CA and that prompt hypothermic therapy could increase the survival rate temporarily after CA, but could not ultimately save the animal.

Effects of regional body temperature variation during asphyxial cardiac arrest on mortality and brain damage in a rat model.

To date, hypothermia has focused on improving rates of resuscitation to increase survival in patients sustaining cardiac arrest (CA). Towards this end, the role of body temperature in neuronal damage or death during CA needs to be determined. However, few studies have investigated the effect of regional temperature variation on survival rate and neurological outcomes. In this study, adult male rats (12 week-old) were used under the following four conditions: (i) whole-body normothermia (37 ± 0.5 °C) plus (+) no asphyxial CA, (ii) whole-body normothermia + CA, (iii) whole-body hypothermia (33 ± 0.5 °C)+CA, (iv) body hypothermia/brain normothermia + CA, and (v) brain hypothermia/body normothermia + CA. The survival rate after resuscitation was significantly elevated in groups exposed to whole-body hypothermia plus CA and body hypothermia/brain normothermia plus CA, but not in groups exposed to whole-body normothermia combined with CA and brain hypothermia/body normothermia plus CA. However, the group exposed to hypothermia/brain normothermia combined with CA exhibited higher neuroprotective effects against asphyxial CA injury, i.e. improved neurological deficit and neuronal death in the hippocampus compared with those involving whole-body normothermia combined with CA. In addition, neurological deficit and neuronal death in the group of rat exposed to brain hypothermia/body normothermia and CA were similar to those in the rats subjected to whole-body normothermia and CA. In brief, only brain hypothermia during CA was not associated with effective survival rate, neurological function or neuronal protection compared with those under body (but not brain) hypothermia during CA. Our present study suggests that regional temperature in patients during CA significantly affects the outcomes associated with survival rate and neurological recovery.

Delta neutrophil index: A reliable marker to differentiate perforated appendicitis from non-perforated appendicitis in the elderly.

BACKGROUND: Delta neutrophil index (DNI) is a new inflammatory marker and the present study aimed to evaluate the predictive value of the DNI for the presence of a perforation in elderly with acute appendicitis. METHODS: This retrospective observational study was conducted on 108 consecutive elderly patients (≥65 years old) with acute appendicitis treated over a 24-month period. RESULTS: Sixty-nine of the 108 patients (median, IQR: 72, 67-77 years) were allocated to the perforated appendicitis group (63.9%) and 39 to the non-perforated appendicitis group (36.1%). WBC, neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio and DNI were significantly higher in the perforated group. In multiple logistic regression analyses, initial DNI was the only independent marker that can significantly predict the presence of perforation in multiple regression [odds ratio 9.38, 95% confidence interval (2.51-35.00), P=.001]. Receiver operator characteristic curve analysis showed that DNI is a good predictor for the presence of appendiceal perforation at an optimal cut-off for DNI being 1.4% (sensitivity 67.7%, specificity 90.0%, AUC 0.807). CONCLUSION: Clinicians can reliably differentiate acute perforated appendicitis from non-perforated appendicitis by DNI level of 1.4 or more in elderly patients.

Neuronal injury and tumor necrosis factor-alpha immunoreactivity in the rat hippocampus in the early period of asphyxia-induced cardiac arrest under normothermia.

Low survival rate occurs in patients who initially experience a spontaneous return of circulation after cardiac arrest (CA). In this study, we induced asphyxial CA in adult male Sprague-Daley rats, maintained their body temperature at 37 ± 0.5°C, and then observed the survival rate during the post-resuscitation phase. We examined neuronal damage in the hippocampus using cresyl violet (CV) and Fluore-Jade B (F-J B) staining, and pro-inflammatory response using ionized calcium-binding adapter molecule 1 (Iba-1), glial fibrillary acidic protein (GFAP), and tumor necrosis factor-alpha (TNF-α) immunohistochemistry in the hippocampus after asphyxial CA in rats under normothermia. Our results show that the survival rate decreased gradually post-CA (about 63% at 6 hours, 37% at 1 day, and 8% at 2 days post-CA). Rats were sacrificed at these points in time post-CA, and no neuronal damage was found in the hippocampus until 1 day post-CA. However, some neurons in the stratum pyramidale of the CA region in the hippocampus were dead 2 days post-CA. Iba-1 immunoreactive microglia in the CA1 region did not change until 1 day post-CA, and they were activated (enlarged cell bodies with short and thicken processes) in all layers 2 days post-CA. Meanwhile, GFAP-immunoreactive astrocytes did not change significantly until 2 days post-CA. TNF-α immunoreactivity decreased significantly in neurons of the stratum pyramidale in the CA1 region 6 hours post-CA, decreased gradually until 1 day post-CA, and increased significantly again 2 days post-CA. These findings suggest that low survival rate of normothermic rats in the early period of asphyxia-induced CA is related to increased TNF-α immunoreactivity, but not to neuronal damage in the hippocampal CA1 region.

The potential mechanism of the detrimental effect of defibrillation prior to cardiopulmonary resuscitation in prolonged cardiac arrest model.

Defibrillation is no longer universally recommended as initial intervention for the reversal of ventricular fibrillation (VF) after a prolonged and untreated cardiac arrest. We sought to examine this issue in an animal model where a prolonged untreated VF was induced. The aim of this study was to investigate the potential mechanism of the detrimental effect of defibrillation prior to cardiopulmonary resuscitation (CPR) in prolonged cardiac arrest model. VF was electrically induced in 32 domestic male swine weighing 40±3 kg and remained untreated for 15 minutes. The animals were then randomly allocated to either the initial defibrillation group or the chest compression group. Mean aortic pressure, right atrial pressure and coronary perfusion pressure (CPP) were continuously measured during the performance. The dimensions of the left ventricle (LV) were assessed by echocardiographic methods. The CPP induced by CPR after defibrillation was significantly lower in the initial defibrillation group than in the chest compression group; 1 minute after defibrillation (9±3 mmHg vs. 14.8±7 mmHg (P<0.05)), and after 5 minutes 16±5 mmHg vs. 21.7±1 mmHg (P<0.05). The LV volumes were reduced from 18±2 mmHg to 14±1 mmHg after defibrillation (P<0.05). In brief, this study showed that the conducting defibrillation prior to chest compression may cause a contracture of the LV, resulting in lowering CPP, thus dropping the efficiency of chest compression in a prolonged cardiac arrest model.

Identification of a novel U2HR mutation in a Korean woman with Marie Unna hereditary hypotrichosis.

Marie Unna hereditary hypotrichosis (MUHH) is a rare autosomal dominant genodermatosis characterized by progressive non-scarring hair loss. Mutation of the U2HR gene, located in chromosome 8p21, is generally responsible for MUHH development. Until now, 17 mutations of U2HR have been identified from various ethnic backgrounds, but U2HR mutations have been identified mostly in Chinese families and only one Japanese patient with MUHH among Asian populations. Here, we report the first Korean case of MUHH with a novel heterozygous missense mutation (c.80C>T) in U2HR that has not been documented to date. Genetic analysis further revealed that this mutation is responsible for the hair morphology phenotype presented in this case. This finding contributes to expansion of the mutant spectrum of U2HR, supporting the possibility of racial differences in terms of genetic mutations of MUHH.