A prolonged stress rat model recapitulates some PTSD-like changes in sleep and neuronal connectivity.

Chronic post-traumatic stress disorder (PTSD) exhibits psychological abnormalities during fear memory processing in rodent models. To simulate long-term impaired fear extinction in PTSD patients, we constructed a seven-day model with multiple prolonged stress (MPS) by modifying manipulation repetitions, intensity, and unpredictability of stressors. Behavioral and neural changes following MPS conveyed longitudinal PTSD-like effects in rats for 6 weeks. Extended fear memory was estimated through fear retrieval induced-freezing behavior and increased long-term serum corticosterone concentrations after MPS manipulation. Additionally, memory retrieval and behavioral anxiety tasks continued enhancing theta oscillation activity in the prefrontal cortex-basal lateral amygdala-ventral hippocampus pathway for an extended period. Moreover, MPS and remote fear retrieval stimuli disrupted sleep-wake activities to consolidate fear memory. Our prolonged fear memory, neuronal connectivity, anxiety, and sleep alteration results demonstrated integrated chronic PTSD symptoms in an MPS-induced rodent model.

Hypocretin role in posttraumatic stress disorder-like behaviors induced by a novel stress protocol in mice.

Introduction: Posttraumatic stress disorder (PTSD) is a psychiatric disorder developed in individuals who expose to traumatic events. These patients may experience symptoms, such as recurrent unwanted memory of the traumatic event, avoidance of reminders of the trauma, increased arousal, and cognitive difficulty. The hypocretinergic system originates from the lateral hypothalamic area (LHA) and projects diffusely to the whole brain, and hypocretin may be involved in the features of stress-related disorder, PTSD. Methods: Our study aimed to investigate the role of basolateral amygdala (BLA) hypocretin signals in the pathophysiology of PTSD-like symptoms induced by the modified multiple-prolonged stress (MPS) protocol. The BLA, a brain region involved in fear-related behaviors, receives the hypocretin projections. In this study, TCS1102, a dual hypocretin receptor antagonist, was used to block the hypocretin signal in BLA. Results: Our data indicated that the MPS protocol is a potential PTSD-like paradigm in mice. Meanwhile, the blockade of hypocretin signaling in the BLA relieved the MPS-induced fear response, and partially reduced PTSD-like anxiety behaviors performed by the open field test (OFT) and elevated plus maze (EPM) task. Discussion: Our findings suggest that the hypocretinergic system is a potential therapeutic approach for PTSD treatment. With further research, the hypocretin-based medication can be a candidate for human PTSD treatment.

Hericium erinaceus mycelium ameliorate anxiety induced by continuous sleep disturbance in vivo.

BACKGROUND: Sleep disruption is a major public health issue and may increase the risk of mortality by ten-folds if an individual is sleeping less than 6 h per night. Sleep has changed dramatically during to the COVID-19 pandemic because COVID symptoms can lead to psychological distress including anxiety. Hericium erinaceus mycelium has been widely investigated in both the in vivo studies and clinical trials for its neuroprotective functions because the mycelium contains hericenones and erinacines, which synthesize the nerve growth factor and brain-derived neurotrophic factor (BDNF). Recent in vivo reports have shown showed that erinacine A-enriched Hericium erinaceus mycelium can modulate BDNF/TrkB/PI3K/Akt/GSK-3ß pathways to induce an antidepressant-like effect. A large body of evidence indicates that erinacine can pass the blood-brain barrier and suggests its neuroprotective function in both peripheral and central nervous systems. Thus, Hericium erinaceus mycelium may be a dual-function supplement for sleep disruption improvement while sustaining anxiolytic effects. METHOD: To simulate the condition of sleep disruption, the mice were subjected to the tail suspension test (TST) for 15 min every day during the same period for nine consecutive days. Two different doses (75 and 150 mg/kg) of Hericium erinaceus mycelium were administered orally 20 min prior to the TSTs before entering the light period of 12:12 h L:D cycle. All sleep-wake recording was recorded for 24 h using electroencephalogram and electromyogram. The elevated-plus-maze and open-field tests were conducted to record the behavior activities. RESULTS: Consecutive TSTs prior to the light period could cause significant sleep disturbance and anxiety behavior in the elevated-plus-maze experiments. Results showed that administration with Hericium erinaceus mycelium at 150 mg/kg ameliorated the rodent anxiety (p < 0.05) and reversed the TST-induced NREM sleep disturbance in the dark period. CONCLUSION: This is the first in vivo study suggesting that Hericium erinaceus mycelium has a dual potential role for anxiety relief through improving sleep disruptions.

Oral Administration of Armillaria mellea Mycelia Promotes Non-Rapid Eye Movement and Rapid Eye Movement Sleep in Rats.

The present study aimed to explore whether water and ethanol extracts of Armillaria mellea mycelia produce sedative and hypnotic effects in rats. Male Sprague-Dawley rats were surgically implanted with two electroencephalogram electrodes on the skull and an electromyogram electrode on neck muscle to evaluate the alterations in rapid eye movement (REM) and non-REM (NREM) sleep after oral administration of the water and ethanol extracts. Following post-surgical recovery, thirty-six rats were randomly divided into four treatment groups and two control groups. They were treated orally with vehicle, 75 and 150 mg/kg doses of water and ethanolic extracts 15 min prior to the onset of dark (active) period. Electroencephalography results showed that the low dose of A. mellea mycelia water extract increased REM sleep time while the high dose enhanced both REM and NREM sleep times during the subsequent light (rest) period. On the other hand, although the low dose of A. mellea mycelia ethanolic extract did not alter both NREM sleep and REM sleep during the dark and light periods, the high dose increased both REM and NREM sleep during the light periods in naive rats. The HPLC-DAD analyses of both extracts allowed the identification of GABA and seven sesquiterpenoids. Based on these findings, the present study showed for the first time that water and ethanolic extracts of A. mellea mycelia, containing a source of biologically active compounds, could increase both NREM sleep and REM sleep during the rest period and may be useful for the treatment of insomnia.

Outcomes of hepatectomy for hepatolithiasis.

AIM: Surgical and nonsurgical procedures for management of hepatolithiasis have been reported. The aim of this study was to evaluate immediate and long-term results of hepatectomy as treatment for hepatolithiasis. MATERIALS AND METHODS: Immediate and long-term outcomes of 123 consecutive patients who underwent hepatectomy for hepatolithiasis at our institution from 2000 to 2005 were analyzed retrospectively. Acute cholangitis was the major presenting symptom (in 106 out of 123, 86.2% of cases). RESULTS: The immediate stone clearance rate was 92.7% (114 out of 123) and final stone clearance rate was 96% (118 out of 123) after subsequent T-tube route or endoscopic retrograde cholangiopancreatography (ERCP). Residual stones were identified in 5 patients (4%). The surgical morbidity and mortality rates were 33.3% (41 out of 123) and 1.6% (2 out of 123) respectively. Of the 123 patients, 3 (2.4%) had associated cholangiocarcinoma at the time of hepatectomy. With a median follow-up of 40.3 months (range 5-58), a recurrent stone developed in 7 patients (5.7%) and cholangiocarcinoma in 2 (1.6%). Ten patients died during the follow-up period, with 4 of them (out of 123, 3.2%) due to recurrent stone with sepsis. CONCLUSION: Hepatectomy is a safe and effective treatment for hepatolithiasis, with a high stone clearance rate and fair rate of surgical complications. Recurrent stone-induced sepsis and cholangiocarcinoma are the major factors compromising long-term survival in these patients.

Anatomic resection for severe blunt liver trauma.

Despite recent advances in management of severe blunt liver trauma, the operative mortality rate in patients with complicated blunt liver trauma (grades IV and V) is still high. The purpose of this study was to assess the results of anatomic liver resection for severe liver trauma in the institution in which liver transplant surgeons are responsible for the management of liver injuries.