Comprehensive behavioral study of C57BL/6.KOR-ApoEshl mice.

Background: Apolipoprotein E (ApoE) is associated with Alzheimer's disease (AD) and cognitive dysfunction in elderly individuals. There have been extensive studies on behavioral abnormalities in ApoE-deficient (Apoeshl) mice, which have been described as AD mouse models. Spontaneously hyperlipidemic mice were discovered in 1999 as ApoE-deficient mice due to ApoE gene mutations. However, behavioral abnormalities in commercially available Apoeshl mice remain unclear. Accordingly, we aimed to investigate the behavioral abnormalities of Apoeshl mice. Results: Apoeshl mice showed decreased motor skill learning and increased anxiety-like behavior toward heights. Apoeshl mice did not show abnormal behavior in the Y-maze test, open-field test, light/dark transition test, and passive avoidance test. Conclusion: Our findings suggest the utility of Apoeshl mice in investigating the function of ApoE in the central nervous system.

Component-specific reduction in perineuronal nets in senescence-accelerated mouse strains.

With increased life expectancy, age-related diseases are a significant health concern in Western societies. Animal models (e.g., rodents) have been used to understand age-related changes in brain function-particularly through the senescence-accelerated mouse (SAM) strain. Previous reports have shown that the senescence-accelerated mouse propensity (SAMP)8 and SAMP10 strains have learning disabilities. In this study, we analyzed the prefrontal cortex, which is involved in cognitive function. We aimed to clarify the changes in parvalbumin-positive interneurons (PV-positive neurons), which are related to cognitive function, and perineuronal nets (PNNs), which are special extracellular matrix molecules formed around them. We performed histological analysis of PV-positive neurons and PNNs in the prefrontal cortex to elucidate the mechanism of behavioral abnormalities in SAMP8 and SAMP10 strains. Expression of Cat-315-positive PNN was not confirmed in the prefrontal cortex of SAMP10 mice. However, the density of AB1031-positive PNN, tenascin-R-positive PNN, and brevican-positive PNN decreased in the prefrontal cortex of SAMP8 and SAMP10 mice compared to that of the senescence-accelerated mouse resistance (SAMR1) mice. In addition, the density of PV-positive neurons was lower in SAMP8 mice than in SAMR1 mice. These mice, which exhibited behavioral and neuropathological phenotypes with age, showed different PV-positive neurons and PNNs in the prefrontal cortex compared with the SAMR1 mice. We believe that the results of this study will be useful for elucidating the mechanisms of age-related decline in cognitive and learning functions using SAM.

The prevention of home-cage grid climbing affects muscle strength in mice.

Experimenters and treatment methods are the major contributors to data variability in behavioral neuroscience. However, home cage characteristics are likely associated with data variability. Mice housed in breeding cages spontaneously exhibit behavioral patterns such as biting into the wire grid and climbing on the grid lid. We aimed to clarify the effect of covering the stainless steel wire grid lid in commonly used home cage with Plexiglas to prevent climbing on muscle strength in mice. Furthermore, we investigated the effects of climbing prevention on activity and anxiety-like behavior, and the impact of climbing prevention during the postnatal development period and adulthood on muscle strength. Muscle strength, anxiety-like behavior, and locomotor activity were assessed by a battery of tests (wire hang, suspension, grip strength, rotarod, elevated-plus maze, and open field tests). Mice prevented from climbing the wire grid during postnatal development displayed lower muscle strength than those able to climb. Moreover, mice prevented from climbing for 3 weeks following maturity had weakened muscles. The muscle strength was decreased with 3 weeks of climbing prevention in even 1-year-old mice. In summary, the stainless steel wire grid in the home cage contributed to the development and maintenance of muscle strength in mice.

Chronic Inhibition of Aggressive Behavior Induces Behavioral Change in Mice.

Suppression of anger is more common than its expression among Asian individuals. Emotional suppression is considered an unhealthy emotional regulation. Most studies on emotional suppression have concluded that suppression adversely affects social outcomes, with approximately 5% of the world's population suffering from emotional disorders. However, anger suppression has not received academic attention, and details of the effects of chronic anger suppression on the central nervous system remain unclear. In this study, we performed the resident-intruder test to investigate the effect of chronic suppression of aggressive behavior in mice using a behavioral test battery and to clarify whether suppression of this aggressive behavior is stressful for mice. Mice chronically inhibited aggressive behavior and lost weight. Mice with inhibited aggressive behavior showed a reduced percentage of immobility time during the tail suspension test as well as no changes in activity, anxiety-like behavior, muscle strength, or temperature sensitivity. This study provides scientific evidence for the effects of chronic aggressive behavior inhibition on the body and central nervous system.

Ryanodine receptors are involved in the improvement of depression-like behaviors through electroconvulsive shock in stressed mice.

BACKGROUND: Electroconvulsive therapy (ECT) is effective for treating depression. However, the mechanisms underlying the antidepressant effects of ECT remain unknown. Depressed patients exhibit abnormal Ca2+ kinetics. Early stages of the intracellular Ca2+ signaling pathway involve the release of Ca2+ from the endoplasmic reticulum (ER) via Ca2+ release channels. OBJECTIVE: We considered that depression may be improved via ECT-induced normalization of intracellular Ca2+ regulation through the Ca2+ release channels. The current study aimed to investigate the effects of ECT on two Ca2+ release channels, ryanodine receptors (RyRs) and inositol 1,4,5-trisphosphate receptors (IP3Rs). METHODS: A mouse depression-like model subjected to water immersion with restraint stress was administered electroconvulsive shock (ECS) therapy. Their depression-like status was behaviorally and histologically assessed using forced swimming tests, novelty-suppressed feeding tests, and by evaluating neurogenesis in the hippocampal dentate gyrus, respectively. A RyRs blocker, dantrolene, was administered prior to ECS, and the changes in depression-like conditions were examined. RESULTS: The protein expressions of RyR1 and RyR3 significantly increased in the hippocampus of the mouse model with depression-like symptoms. This increase was attenuated as depression-like symptoms were reduced due to ECS application. However, pre-injection with dantrolene reduced the antidepressant effects of ECS. CONCLUSIONS: A significant increase in RyRs expression in a depression-like state and exacerbation of depression-like symptoms by RyRs inhibitors may be caused by RyRs dysfunction, suggesting overexpression of RyRs is a compensatory effect. Normalization of RyRs expression levels by ECS suggests that ECT normalizes the Ca2+ release via RyRs. Thus, normalizing the function of RyRs may play an important role in the therapeutic effect of ECT.

An Autopsy Case of Injuries Caused by Automobile Dragging for a Distance of 3.4 km Without Thoracoabdominal Organ Injuries.

Dragging injuries caused by automobiles involved in an accident are occasionally reported; however, those without injury to the thoracoabdominal organs are rare. We present an autopsy case of a man in his 20s found dead on the road after being dragged by a passenger automobile for a distance of 3.4 km. The accident caused fatal dragging injuries but no thoracoabdominal injuries. The victim appeared to be drunk and was lying on the road in front of the parked automobile. Dragging injuries are a unique type of traffic accident that sometimes result from limited and poor visibility due to darkness, rain, or fog. In particular, lying on the road in a drunken state is a specific risk factor for dragging injuries. The dragging distance, road-surface properties, strength of pressure applied by the underbody of the automobile, and the victim's posture are considered to affect the distribution and degree of dragging injuries. Based on autopsy findings and eyewitness testimonies, we discuss the injury mechanism and attempt to reconstruct the accident.

Pilsicainide Poisoning: An Autopsy Case and Review of Literature.

We describe an autopsy case of fatal poisoning due to accidental overdose of pilsicainide, which is a Vaughan Williams class IC antiarrhythmic drug (a pure sodium channel blocker). A man in his 50s was found dead in his home at approximately noon. He had ischemic heart disease and insomnia, and had previously demonstrated improper prescription drug adherence. The autopsy revealed old coronary artery bypass grafting and mild fibrosis of myocardium, but no acute myocardial infarction was found in microscopic examination. Toxicological analysis also identified a high blood concentration of pilsicainide (femoral vein blood, 14.9 µg/mL), more than 15 times higher than reported therapeutic levels. The blood concentrations of other drugs were at therapeutic levels, and no alcohol was detected. We concluded that the cause of death was pilsicainide poisoning, based on the results of the autopsy and the toxicological examination. This is the first autopsy report of fatal poisoning due to pilsicainide as a single agent.

Nontraumatic Convexal Subarachnoid Hemorrhage Accompanied by Sylvian Hematoma: An Autopsy Case of Ruptured Distal Middle Cerebral Artery Aneurysm.

We describe an autopsy case of nontraumatic convexal subarachnoid hemorrhage (cSAH) accompanied by sylvian hematoma. A woman in her 50s was found dead in her house. On autopsy, massive cSAH accompanied by sylvian hematoma was observed. Because of the absence of subarachnoid hemorrhage (SAH) in the basal cistern, initial suspicion was that of a traumatic SAH. After a detailed investigation, a ruptured cerebral aneurysm of the distal middle cerebral artery was found in the hematoma, and the cSAH in this case was confirmed to be endogenous. Convexal subarachnoid hemorrhages typically result from traumatic injury, whereas endogenous cSAHs are exceedingly rare. Autopsy findings of a sylvian hematoma with SAH may result from endogenous hemorrhage from ruptured aneurysm of the distal middle cerebral artery. Detailed investigation of the hematoma may help identify the culprit lesion and help arrive at the correct postmortem diagnosis.

An experimental study of postmortem decomposition of methomyl in blood.

Methomyl (S-methyl-1-N-[(methylcarbamoyl)oxy]thioacetimidate) is a carbamate pesticide. It has been noted that in some cases of methomyl poisoning, methomyl is either not detected or detected only in low concentrations in the blood of the victims. However, in such cases, methomyl is detected at higher concentrations in the vitreous humor than in the blood. This indicates that methomyl in the blood is possibly decomposed after death. However, the reasons for this phenomenon have been unclear. We have previously reported that methomyl is decomposed to dimethyl disulfide (DMDS) in the livers and kidneys of pigs but not in their blood. In addition, in the field of forensic toxicology, it is known that some compounds are decomposed or produced by internal bacteria in biological samples after death. This indicates that there is a possibility that methomyl in blood may be decomposed by bacteria after death. The aim of this study was therefore to investigate whether methomyl in blood is decomposed by bacteria isolated from human stool. Our findings demonstrated that methomyl was decomposed in human stool homogenates, resulting in the generation of DMDS. In addition, it was observed that three bacterial species isolated from the stool homogenates, Bacillus cereus, Pseudomonas aeruginosa, and Bacillus sp., showed methomyl-decomposing activity. The results therefore indicated that one reason for the difficulty in detecting methomyl in postmortem blood from methomyl-poisoning victims is the decomposition of methomyl by internal bacteria such as B. cereus, P. aeruginosa, and Bacillus sp.

Investigation of an anatomically variant isolated bicuspid pulmonary valve: A case report.

INTRODUCTION: We provide a discussion of the anatomical characteristics of the bicuspid pulmonary valve (BPV) in this paper. We performed an autopsy of an isolated BPV found in the heart of a deceased individual. The deceased was a man in his 60s and had no previous history of cardiovascular disease. The heart weighed 260 g and had mild right ventricular hypertrophy. The pulmonary valve had a fish-mouth-like shape that was convex to the pulmonary trunk and both cusps were thickened and hardened. The anterior and left semilunar cusps of the pulmonary valve were fused. Post-stenotic dilatation was noted. CONCLUSIONS: In comparing the present case with previous reports, we found that, in human BPVs, cusps are fused in at least 2 patterns.

Temporal changes of the adrenal endocrine system in a restraint stressed mouse and possibility of postmortem indicators of prolonged psychological stress.

We investigated temporal changes of adrenal endocrine systems through the hypothalamic-pituitary-adrenal (HPA) and sympathetic-adrenomedullary (SA) axis in restraint stressed mice. Restraint stress for 1 day to 3 weeks caused a significant increase in serum levels of ACTH and glucocorticoids accompanied with an increase in adrenal weights, indicating activation of the HPA axis. Reflecting the overproduction of glucocorticoids, adrenal cholesterol content decreased. Moreover, adrenal gene expression involved in cholesterol supply, including scavenger receptor-class B type I, HMG-CoA reductase, and hormone-sensitive lipase, was increased over the same period. After 4 weeks stress, all of these changes returned to control levels. In contrast, adrenal gene expression of chromogranin A, which is cosecreted with catecholamine via the SA axis, was increased with 1 day to 2 weeks of stress, and decreased with 3-4 weeks of stress. Our results suggest that analyses of adrenal endocrine systems based on the combination of several markers examined here would be useful for not only proving prolonged psychological stress experience but also determining its duration.

Anaphylactic shock caused by sting of crown-of-thorns starfish (Acanthaster planci).

A 40s-year-old woman with previous history of injury due to contact with crown-of-thorns starfish, Acanthaster planci, was stung on the right middle finger. After immediately losing consciousness, she died 13 h after injury despite intensive medical treatment. Examination of the respiratory system revealed narrowing due to severe edema of the laryngopharynx, as well as alveolar hemorrhage, eosinophilic infiltration, and extensive neutrophil and eosinophil aggregation in the intravascular lumen of the lungs. Examination of the liver revealed severe diffuse hepatocellular necrosis and extremely high levels of liver transaminases, indicating severe liver damage. Based on these findings, we concluded that she had died from anaphylactic shock induced by circulation of crown-of-thorns starfish venom in the bloodstream. Injurious contact with the spine of the crown-of-thorns starfish can cause severe symptoms as well as systematic reactions, including anaphylaxis. To our knowledge, this is the first case of anaphylactic shock or death caused by human contact with the crown-of-thorns starfish reported in the English-language literature. Although rare, anaphylaxis due to injury by marine animals is potentially fatal. Saving lives requires providing education regarding prevention and enabling prompt response to possible anaphylaxis, including preparation of adrenaline for auto-injection.

Detection of imidacloprid in biological fluids in a case of fatal insecticide intoxication.

Here, we describe a high-performance liquid chromatography/photodiode array detector method for the detection of imidacloprid in biological fluids in a case of suicide by ingestion of liquor mixed with Admire® Flowable insecticide (containing 20% imidacloprid). A plastic bottle containing a cloudy liquid (concentration of ethanol in the liquid was 150 mg/ml and that of imidacloprid was 50 mg/ml) was found near the decedent. The biological fluids collected at autopsy were prepared by deproteinization with acetonitrile. Zolpidem was used as an internal standard. The concentrations of imidacloprid in femoral blood and cerebrospinal fluid were 105 and 58.5 µg/ml, respectively. Ethanol was also detected in the samples, with concentrations of 1.0 mg/ml in femoral blood and 1.4 mg/ml in cerebrospinal fluid.

Morphologic investigation of injury caused by locally applied negative pressure in a rat model.

Although some previous studies have reported patients who developed compartment syndrome or died because of locally applied negative pressure, no detailed investigation of pathologic changes caused by negative pressure-induced injury has been reported in the literature. The main purpose of this study was to examine the morphologic characteristics of injury caused by local negative pressure and correlate these with systemic changes. A total of 30 male Wister rats were used. Animals were randomly assigned to 6 groups. Negative pressure was applied to the right hindlimb of each animal in each group for periods of 0 (sham-operated), 30, 60, 90, 120, or 180 min using a vacuum pump. Macroscopic and microscopic changes induced by local negative pressure were already observed after 30 min and were exacerbated with time. The proportion of muscle degeneration was highest in the deep tissues, irrespective of exposure time. The observed increase in the weight of the injured hindlimb at 180 min was caused by an approximately 30% fluid shift to the hindlimb, demonstrating that the application of negative pressure to the hindlimb of rats can induce hypovolemic shock. We here reveal the morphologic changes induced by local negative pressure and discuss possible mechanisms of negative pressure-induced injury.

A transnasal intracranial stab wound by a plastic-covered umbrella tip.

A 48-year-old man died from a transnasal intracranial stab wound caused by an umbrella. The track of the stab passed from the right nostril, through the sphenoid sinus, the left side of the sella turcica and anterior clinoid process, and finally reached the surface of the brain. The stab wound crossed the left internal carotid artery, causing an exsanguination and aspiration of blood into the airway, resulting in death. It is extremely rare that an umbrella tip used during a struggle would stab the nostril of the victim. Transnasal intracranial stab wounds can be overlooked and require sensitive handling.

Peritoneal bleeding due to percutaneous transhepatic gallbladder drainage: An autopsy report.

A 77-year-old man underwent percutaneous transhepatic gallbladder drainage (PTGBD) for acute cholecystitis as a preoperative procedure; however, he suddenly suffered cardiopulmonary arrest 4 h after the PTGBD and died. There were three centesis scars for the PTGBD, and only one pathway from the most dorsal centesis scar reached the gallbladder. Microscopically, the PTGBD pathway crossed and injured the intrahepatic arterial wall, and hepatic parenchymal bleeding extended along the PTGBD pathway to the inferior surface of the liver. Blood flowed to the peritoneal cavity through a small gap between the liver and gallbladder. Consequently, the PTGBD caused lethal bleeding. When the percutaneous transhepatic cholangio drainage/PTGBD pathway runs close to vessels near the liver surface, it might be necessary to deal with the possibility of rapid and lethal peritoneal bleeding.

An autopsy case of suction injury.

The right upper extremity of a 38-year-old man was entrapped in an underwater intake of a water duct of a dam reservoir, and he died despite being promptly rescued. His right upper extremity was swollen and exhibited purplish-red discolourations. The skin had numerous blisters and increased tension. Severe subcutaneous and muscle bleeding were observed in the right upper extremity. The circumference and volume of the right upper extremity were approximately 1.2 and 1.4 times, respectively, that the circumference and volume of the left upper extremity. The increase in weight of the right extremity was calculated to be approximately 2.1 kg; this finding indicates a severe decrease in the victim's central blood volume. Furthermore, it is possible that much more than 2.1 kg of blood accumulated in the upper extremity upon exposure to vacuum pressure. We conclude that the victim died of circulatory collapse that was attributable to haemorrhage and re-distribution of blood as a result of vacuum pressure on the right upper extremity. Thus, we have examined the cause of death and the effects of vacuum pressure on the human body.

Fatal propeller injuries: three autopsy case reports.

Most propeller injuries occur at water recreational facilities such as those with provision for water skiing, boat racing, skin and scuba diving. Propeller injuries resulting from nautical accidents can be fatal. The sharp blades of propellers rotating at high speeds cause multiple and serious injuries such as deep laceration, chop wounds, bone fractures and mutilation of extremities. We present the autopsy reports of three people who died after colliding with boat propellers.

Characteristic features of injuries due to shark attacks: a review of 12 cases.

Shark attacks on humans might not occur as often as is believed and the characteristic features of shark injuries on corpses have not been extensively reviewed. We describe the characteristic features of shark injuries on 12 corpses. The analysis of these injuries might reveal the motivation behind the attacks and/or the shark species involved in the attack. Gouge marks on the bones are evidence of a shark attack, even if the corpse is decomposed. Severance of the body part at the joints without a fracture was found to be a characteristic feature of shark injuries.