Importance of home cage condition for contextual fear memory, fear extinction and spontaneous recovery: Cage size and bedding material.

Home cage condition influences the central nervous system of experimental animals. However, little is known about the effect of home cage size and bedding material on fear-related behaviors. Thus, in this study, the effects of home cage size (large or small) and/or bedding material (paper or wood) on acquisition, retrieval, extinction, and spontaneous recovery of contextual fear memory were investigated in both male and female mice. The present study demonstrated that males housed in small cages with wood bedding showed a low fear response during fear extinction when compared to males housed in small or large cages with paper bedding. In females, mice housed in small cages with wood bedding showed low fear response during fear conditioning and extinction when compared to mice housed in large cages with paper bedding. Moreover, small cages with wood bedding, but not small or large cages with paper bedding, prevented the spontaneous recovery of fear memory in females. Thus, home cage conditions, and particularly bedding material, influence contextual fear extinction and spontaneous recovery. This finding may help to obtain reproducibility of results by researchers and explain discrepancies of results among research groups.

Association of the body mass index with poor outcome at discharge in patients with aneurysmal subarachnoid hemorrhage: a registry study.

Although several studies have reported on the impact of the body mass index (BMI) on functional outcome of aneurysmal subarachnoid hemorrhage (aSAH), the relationship remains unclear. This study aimed to investigate the risk factors of poor outcome of aSAH, with particular attention to BMI. A total of 860 patients with aSAH were enrolled in our registry at Shimane Prefectural Central Hospital between 2000 and 2017, of whom 393 were included in the analysis. Basic patient characteristics, including BMI, and data related to aSAH were recorded. We conducted a univariable analysis, followed by a multivariable analysis to identify the risk factors of poor outcome, defined as a modified Rankin Scale score > 2 at discharge. We also compared our study with previous studies that reported a relationship between BMI and aSAH. Multivariable analysis revealed that age (odds ratio [OR], 1.09; 95% confidence interval [CI], 1.07-1.12), underweight (OR, 2.36; 95% CI, 1.13-4.90), overweight (OR, 2.22; 95% CI, 1.06-4.64), World Federation of Neurosurgical Societies grade (III vs I: OR, 3.10; 95% CI, 1.03-9.35; IV vs I: OR, 8.02; 95% CI, 3.54-18.19; V vs I: OR, 13.37; 95% CI, 5.33-33.54), and symptomatic vasospasm (OR, 3.40; 95% CI, 1.73-6.70) were risk factors for poor outcome at discharge. This study showed the association of underweight (BMI < 18.5 kg/m2) and overweight (≥ 25 kg/m2) with poor outcome; therefore, both high and low BMI are associated with a poor outcome at discharge for patients with aSAH. Clinical trial registry: University Hospital Medical Information Network (UMIN000035160; date of registration: December 6, 2018).

Different Risk Factors Between Cerebral Infarction and Symptomatic Cerebral Vasospasm in Patients with Aneurysmal Subarachnoid Hemorrhage.

OBJECTIVE: Cerebral infarction due to cerebral vasospasm (IVS) after aneurysmal subarachnoid hemorrhage is associated with poor outcomes and symptomatic cerebral vasospasm (SVS). However, the difference of risk factors between SVS and IVS was unclear to date. In this study, we aimed to elucidate the risk factors for SVS and IVS based on the registry study. METHODS: The modified World Federation of Neurosurgical Societies scale study comprises 1863 cases. Patients with aneurysmal subarachnoid hemorrhage who underwent radical treatment within 72 hours with a premorbid modified Rankin Scale score 0-2 as the inclusion criteria were retrospectively examined. The risk factors for SVS and IVS were analyzed using multivariable logistic regression analysis. RESULTS: Among them, 1090 patients who met the inclusion criteria were divided into 2 groups according to SVS and IVS; 273 (25%) patients with SVS and 92 (8.4%) with IVS. Age was not a risk factor for SVS, but for IVS, and Fisher scale was a risk factor for SVS, but not for IVS. CONCLUSIONS: The prevalence of IVS was not associated with the Fisher scale but with older age, suggesting possible factors other than SVS. Different associated factors between SVS and IVS were confirmed in this study.

Perioperative Surgical Risks in Patients With Hemangioblastomas: A Retrospective Nationwide Review in Japan.

BACKGROUND: The perioperative risk of sporadic hemangioblastomas (HBs) and von Hippel-Lindau disease (VHL)-associated hemangioblastomas (VHL-associated HBs) remains unclear due to the rare prevalence of HB. Therefore, this study aimed to clarify risk factors for better surgical management of patients with HBs. METHODS: A retrospective analysis of surgically treated HB patients registered in the Diagnosis Procedure Combination database of Japan, between 2010 and 2015, was performed. Age, sex, sporadic HBs or VHL-associated HBs, medical history, tumor location, hospital case load, postoperative complications, and Barthel index (BI) deterioration were assessed. We also evaluated the outcomes and factors of perioperative BI deterioration. RESULTS: In total, 676 patients with 609 intracranial lesions, 64 spinal lesions, and 3 with both types were eligible. Among them, 618 and 58 patients had sporadic HBs and VHL-associated HBs, respectively. The rates of perioperative BI deterioration were 12.5% and 12.2% for sporadic HBs and VHL-associated HBs, respectively. Perioperative mortality was 1.8% and 0% for sporadic HBs and VHL-associated HBs, respectively. Male sex, old age, high hospital case load, and medical history of diabetes mellitus were significantly associated with perioperative BI deterioration in all cases and sporadic HBs. Only medical history of diabetes mellitus was a significant risk factor for perioperative BI deterioration in VHL-associated HBs. CONCLUSIONS: No differences in perioperative BI deterioration rates between sporadic HBs and VHL-associated HBs were found. However, different risk factors for perioperative BI deterioration were identified. Consideration of these risk factors is recommended in all patients undergoing surgery for HB.

[Research for sex differences in fear extinction].

Fear memory has an important role in survival, but excess fear memory could be cause to fear-related disorders such as post traumatic disorder (PTSD). People who undergo a fearful event do not always develop PTSD, suggesting that there are vulnerable factors to develop the disorder. It is believed that sex, in particular female, is one of the factors as it is known that the prevalence rate of PTSD is higher in women than in men. However, the biological mechanisms underlying the sex differences in their prevalence rate remain unclear. Because previous studies reported that patients with fear-related disorders show an impairment of fear extinction, investigation of sex differences in fear extinction may be useful for understanding the greater vulnerability of women to fear-related disorders. Although number of papers investigating sex differences in fear extinction, these reports have increased recently. This review introduces fear extinction, sex differences in fear extinction is low, and the molecular mechanisms of sex differences in fear extinction. In the molecular mechanisms, we focused brain-derived neurotrophic factor (BDNF)-tropomyosin-related kinase B (TrkB) receptor signal which has been investigated by independent research groups.

Factors associated with the location of perivascular space enlargement in middle-aged individuals undergoing brain screening in Japan.

OBJECTIVE: In elderly populations, the enlargement of the perivascular space is related to small vessel disease and the glymphatic system. Enlarged perivascular spaces (EPVS) in the basal ganglia (EPVS-BG) and EPVS in the centrum semiovale (EPVS-CSO) are associated with different pathophysiological processes. However, the prevalence of EPVS and the factors associated with EPVS location in healthy middle-aged individuals are still unclear. We aimed to determine the prevalence of EPVS and the factors associated with EPVS location among healthy individuals in their 40 s METHODS: This study included 5000 consecutive healthy individuals who underwent screening for brain diseases in Japan from August to December 2018. Of them, the data of individuals in their 40 s were extracted and analyzed. The associations of age, sex, body mass index, smoking and drinking history, and medical history with EPVS location were investigated. Similar analyses were performed for the other age groups. A literature review on the factors associated with EPVS location was also performed. RESULTS: A total of 1720 individuals in their 40 s were finally included. The prevalence of EPVS-BG and EPVS-CSO was 7.7% and 9.2%, respectively. Age (years), smoking history, and hypertension were associated with EPVS-BG; none of the studied factors were found to be associated with EPVS-CSO. In the elderly, the factors previously reported to be associated with EPVS-BG included atherosclerosis change, while the factors associated with EPVS-CSO were cerebral amyloid angiopathy-related formation. CONCLUSION: Both EPVS-BG and EPVS-CSO occurred among healthy individuals in their 40 s, but they did so rarely, and less prevalently than in older age groups. EPVS-BG and EPVS-CSO may represent early imaging signs of the atherosclerotic and cerebral amyloid angiopathy processes, respectively. DATA AVAILABILITY: The anonymized data for this study will be shared upon any qualified investigator's request to the corresponding author. Primary data from this study will be made available upon reasonable request in accordance with the review board of the research institute.

Recent Declining Trend of Incidence Rate of Subarachnoid Hemorrhage in Shimane, Japan: The Japan Incidence of Subarachnoid Hemorrhage (JIS) Study.

The "Izumo Study" revealed the incidence rate of subarachnoid hemorrhage (SAH) in Izumo City, Shimane Prefecture, Japan, from 1980 to 1998. However, no study has been published regarding the incidence of SAH in Shimane Prefecture after 1998. Most studies reporting the incidence of SAH in Japan have been conducted before 2000, although a few have been reported after 2000. This study aimed to assess the estimated age-adjusted incidence rate (AAIR) of SAH in Shimane Prefecture after 1998, following the Izumo Study. A retrospective study was conducted to identify the estimated AAIR of SAH in Shimane Prefecture, using the age-adjusted SAH mortality rate for this population from 1999 to 2017 and assuming that the case-fatality rate of SAH decreased by 0.7% annually from 45% in 1999 to 32.4% in 2017. We used linear regression analysis for trend to the estimated AAIR of SAH. Sensitivity analyses were also conducted by various case-fatality rates of SAH using assuming case-fatality rate based on previous reports. The estimated AAIR of SAH in Shimane Prefecture declined from 33.6 (95% confidence interval [CI]: 29.7-37.9) per 100,000 person-years in 1999, by 26.5%, to 24.7 (95% CI: 21.4-28.5) in 2017 (p < 0.01, r = 0.58). Declining trend of incidence rate of SAH in Shimane Prefecture from 1999 to 2017 was confirmed in this study.

Changes in Short-Term Outcomes After Discharge in Patients with Aneurysmal Subarachnoid Hemorrhage: A Multicenter, Prospective, Observational Study.

OBJECTIVE: The objective of the study was to clarify the prevalence of and factors associated with changes in patients' outcomes between discharge and 3 months after the onset of aneurysmal subarachnoid hemorrhage (aSAH). Additionally, the World Federation of Neurosurgical Societies (WFNS) and modified WFNS (mWFNS) scales were compared. METHODS: The data of curatively treated patients with aSAH, collected prospectively in the mWFNS scale study between January 2010 and December 2012, were analyzed retrospectively. The improvement or decline in the modified Rankin Scale (mRS) scores between discharge and 3 months after onset was determined. A multivariable logistic regression analysis was performed to identify factors, such as age and WFNS and mWFNS grades, associated with changes in the outcome. RESULTS: The mRS scores improved in 28.3% and declined in 2.5% of the patients. WFNS and mWFNS grades Ⅱ-V on admission were significantly associated with improved mRS scores at 3 months after onset. Older age (age: 65-74 years vs. age <65 years, odds ratio: 6.59, 95% confidence interval: 1.28-34.01; age ≥75 years vs. age <65 years, odds ratio: 17.67, 95% confidence interval: 2.11-148.26) and WFNS grade III were significantly associated with a decline in mRS scores at 3 months after onset. CONCLUSIONS: The optimal timing for postdischarge assessment of outcomes may be at 3 months after onset, especially in older patients with aSAH. The mWFNS scale is presumed to more accurately assess the outcomes of patients with aSAH than the WFNS scale, as demonstrated in this study.

Hypertension and Advanced Age Increase the Risk of Cognitive Impairment after Mild Traumatic Brain Injury: A Registry-Based Study.

BACKGROUND: As the global population ages, the incidence of traumatic brain injury (TBI) is increasing. Whereas mild TBI can impair the cognitive function of older adults, the cause and background of mild TBI-induced cognitive impairment remain unclear, and the evaluation of risk factors for cognitive impairment after mild TBI remains open for consideration, especially in the aging population. This study aimed to evaluate the risks associated with cognitive impairment following mild TBI. METHODS: Between January 2006 and December 2018, a total of 2209 patients with TBI required hospitalization in Shimane Prefectural Central Hospital. Mild TBI was defined as a Japan Coma Scale ≤10 at admission. Patients' cognitive function was measured with the Hasegawa Dementia Rating Scale-Revised or Mini-Mental State Examination at least twice during the patients' hospital stays. The odds ratio (OR) and 95% confidence interval (CI) of each considered risk factor was calculated with multivariable logistic regression analysis after univariate analysis. RESULTS: Among 1674 patients with mild TBI, 172 patients underwent cognitive function examinations, of whom 145 (84.3%) were found to have cognitive impairment at discharge. Significant risk factors for cognitive impairment included age (P = 0.008) and hypertension (P = 0.013) in univariate analysis; and age (OR, 1.04: 95% CI, 1.01-1.07) and hypertension (OR, 5.81: 95% CI, 1.22-27.68) by multivariable analysis. CONCLUSIONS: Older patients with hypertension displayed a significantly higher risk for cognitive impairment after even mild TBI. These patients warrant careful management after even mild TBI.

The role of the cannabinoid system in fear memory and extinction in male and female mice.

The prevalence of post-traumatic stress disorder (PTSD) is higher in women than in men. Among both humans and mice, females exhibit higher resistance to fear extinction than males, suggesting that differences between sexes in fear-extinction processes are involved in the pathophysiology of such fear-related diseases. Sex differences in molecular mechanisms underlying fear memory and extinction are unclear. The cannabinoid (CB) system is well known to be involved in fear memory and extinction, but this involvement is based mainly on experiments using male rodents. It is not known whether there are sex differences in the role of the CB system in fear memory and extinction. To explore this possibility, we investigated the effects of pharmacological manipulations of the CB system on the retrieval and extinction of contextual fear memory in male and female mice. WIN55,212-2, a CB receptor (CBR) agonist, augmented the retrieval of fear memory in both sexes, but SR141716 (a CB1R antagonist) did not affect it in either sex. An enhancement of 2-arachidonylglycerol (2-AG, one of the two major endocannabinoids) via JZL184 (an inhibitor of the 2-AG hydrolase monoacylglycerol lipase [MAGL]), augmented the retrieval of fear memory through the activation of CB1R but not CB2R in female mice. In contrast, the enhancement of N-arachidonylethanolamine (AEA, the other major endocannabinoid) via URB597, an inhibitor of an AEA hydrolase (fatty acid amide hydrolase-1) did not show any effects on the retrieval of fear memory in either sex. WIN55,212-2, SR141716, and JZL184 inhibited fear extinction irrespective of sex. URB enhanced fear extinction in females that were in diestrus phase at the first extinction session, but not in males. These results suggest that although the role of CB1R in the retrieval and extinction of contextual fear memory is common among males and females, the effects of an increase in endocannabinoid levels on the retrieval or extinction of contextual fear memory differ between the sexes.

The role of endocannabinoids in consolidation, retrieval, reconsolidation, and extinction of fear memory.

Endocannabinoids are involved in various physiological functions, including synaptic plasticity and memory, and some psychiatric disorders, such as posttraumatic stress disorder (PTSD), through the activation of cannabinoid (CB) receptors. Patients with PTSD often show excessive fear memory and impairment of fear extinction (FE). It has been reported that the stability of acquired fear memory is altered through multiple memory stages, such as consolidation and reconsolidation. FE also affects the stability of fear memory. Each stage of fear memory formation and FE are regulated by different molecular mechanisms, including the CB system. However, to the best of our knowledge, no review summarizes the role of the CB system during each stage of fear memory formation and FE. In this review, we summarize the roles of endocannabinoids in fear memory formation and FE. Moreover, based on the summary, we propose a new hypothesis for the role of endocannabinoids in fear regulation, and discuss treatment for PTSD using CB system-related drugs.

Prevalence and risk factors for brain white matter changes in young and middle-aged participants with Brain Dock (brain screening): a registry database study and literature review.

This study aimed to determine the prevalence and risk factors for brain white matter changes in normal young and middle-aged participants who underwent Brain Dock (brain screening). We analyzed 5,000 consecutive healthy participants from the Brain Dock registry between August to December 2018. Age, sex, body mass index (BMI), medical history, deep subcortical white matter high intensity (DSWMH), periventricular high intensity (PVH), and enlargement of perivascular space (EPVS) were investigated in relation to age. The prevalence of DSWMH, PVH, and EPVS were 35.3%, 14.0%, and 17.8%, respectively. Multivariate logistic regression analyses for brain white matter changes were conducted. The significant risk factors in participants aged < 50 years were: age (OR:1.09, 95% CI:1.07-1.12), the female sex (1.29, 1.03-1.60), BMI obesity (1.86, 1.12-3.08), and hypertension (1.67, 1.18-2.35) for DSWMH; age (1.08, 1.04-1.13) and the female sex (1.56, 1.03-2.36) for PVH; and age (1.07, 1.05-1.10) and the female sex (0.77, 0.60-1.00) for EPVS. In conclusion, age was consistently identified as a significant risk factor in young and middle-aged participants. Some risk factors for brain white matter changes were identified even in young and middle-aged participants in this study. Further longitudinal studies should be done in the future.

Development and Validation of Scoring Indication of Surgical Clipping and Endovascular Coiling for Aneurysmal Subarachnoid Hemorrhage from the Post Hoc Analysis of Japan Stroke Data Bank.

There are no scoring methods for optimal treatment of patients with aneurysmal subarachnoid hemorrhage (aSAH). We developed a scoring model to predict clinical outcomes according to aSAH risk factors using data from the Japan Stroke Data Bank (JSDB). Of 5344 patients initially registered in the JSDB, 3547 met the inclusion criteria. Patients had been diagnosed with aSAH and treated with surgical clipping or endovascular coiling between 1998 and 2013. We performed multivariate logistic regression for poor outcomes at discharge, indicated by a modified Rankin Scale (mRS) score >2, and in-hospital mortality for both treatment methods. Based on each risk factor, we developed a scoring model assessing its validity using another dataset of our institution. In the surgical clipping group, scoring criteria for aSAH were age >72 years, history of more than once stroke, World Federation of Neurological Societies (WFNS) grades II-V, aneurysmal size >15 mm, and vertebrobasilar artery (VBA) aneurysm location. In the endovascular coiling group, scoring criteria were age >80 years, history of stroke, WFNS grades III-V, computed tomography (CT) Fisher group 4, and aneurysmal location in the middle cerebral artery (MCA) and anterior cerebral artery (ACA). The rates of poor outcome of mRS score >2 in an isolated dataset using these scoring criteria were significantly correlated with our model's scores, so this scoring model was validated. This scoring model can help in the more objective treatment selection in patients with aSAH.

Aging Changes of Aneurysmal Subarachnoid Hemorrhage: A 35-year, Hospital-Based Study.

BACKGROUND: The etiology and background factors which cause decreases in the size of ruptured intracranial aneurysms remain unclear. OBJECTIVE: To clarify the age- and sex-related differences in aneurysmal subarachnoid hemorrhage (SAH) based on a 35-year-old hospital database and demographic data. METHODS: A database of patients admitted to our hospital with aneurysmal SAH from 1983 to 2017 was split into 5-year intervals and analyzed. Demographic data of the general population were also analyzed for reference. RESULTS: Altogether, 1,523 aneurysmal SAH events were enrolled in the analysis. Age (p<0.001), proportion of elderly patients ≥ 65 years old (p<0.001), female sex (p=0.005), very small aneurysms less than 5 mm (p<0.001), and the yearly-averaged number of fatal events showed increasing trends. The proportion of aneurysm size of 10 mm or more (p = 0.011) and the yearly-averaged population of Shimane prefecture (p < 0.001) showed declining trends. In the subgroup analyses, the proportion of very small aneurysms was found to increase significantly in the non-elderly male and elderly female subgroups. The proportion of large aneurysms (10 mm or more) decreased in the non-elderly subgroup (p<0.05). As for the elderly subgroups, the yearly-averaged number of events did not show a significant tendency, although the yearly-averaged population of Shimane prefecture showed an increasing trend. CONCLUSION: We found an increasing trend in the prevalence of very small aneurysms in elderly females. Recent aging may contribute to this trend. The number of aneurysmal SAH events was confirmed to not increase, despite the increased aging population of Shimane prefecture.

Deep learning-based classification of the mouse estrous cycle stages.

There is a rapidly growing demand for female animals in preclinical animal, and thus it is necessary to determine animals' estrous cycle stages from vaginal smear cytology. However, the determination of estrous stages requires extensive training, takes a long time, and is costly; moreover, the results obtained by human examiners may not be consistent. Here, we report a machine learning model trained with 2,096 microscopic images that we named the "Stage Estimator of estrous Cycle of RodEnt using an Image-recognition Technique (SECREIT)." With the test dataset (736 images), SECREIT achieved area under the receiver-operating-characteristic curve of 0.962 or more for each estrous stage. A test using 100 images showed that SECREIT provided correct classification that was similar to that provided by two human examiners (SECREIT: 91%, Human 1: 91%, Human 2: 79%) in 11 s. The SECREIT can be a first step toward accelerating the research using female rodents.

Risk Factor for Poor Outcome in Elderly Patients with Aneurysmal Subarachnoid Hemorrhage Based on Post Hoc Analysis of the Modified WFNS Scale Study.

OBJECTIVE: There is currently no precise guide for the treatment and management of elderly patients with aneurysmal subarachnoid hemorrhage (aSAH). Thus, the aim of this study was to clarify the factors of poor outcome and mortality in elderly patients with aSAH. METHODS: In the modified World Federation of Neurosurgical Societies (mWFNS) scale study, 1124 patients were divided into 2 groups, elderly (age ≥65 years) and non-elderly (age <65 years), with aSAH investigated between October 2010 and March 2013 in Japan. The odds ratio (OR) and 95% confidence interval (CI) of each risk factor was calculated through multivariate logistic regression analysis for poor outcomes, as indicated by the modified Rankin Scale (mRS) score ≥3 and mortality at 3 months after onset in each group. RESULTS: Both groups demonstrated that the mWFNS scale was significant as a grade order risk factor for poor outcomes and mortality associated with disease. In the elderly group, risk factors for poor outcomes at 3 months after onset were older age (OR 1.10, 95% CI 1.06-1.14), male sex (OR 2.03, 95% CI 1.10-3.73), and severe cerebral vasospasm category (OR 10.13, 95% CI 4.30-23.87). Risk factors for mortality at 3 months after onset were older age (OR 1.06, 95% CI 1.01-1.11) and severe vasospasm category (OR 2.17, 95% CI 1.00-4.72). CONCLUSIONS: The mWFNS scale is a useful prognostic predictor for both non-elderly and elderly patients with aSAH. Elderly male patients with aSAH presenting with severe vasospasm should be managed more carefully.

Sex-dependent opposite effects of a tropomyosin-related kinase B receptor (TrkB) agonist 7,8-dihydroxyflavone on cued fear extinction in mice.

Tropomyosin-related kinase B receptor (TrkB) is one of the new candidate receptors for drugs targeting psychiatric and neurodegenerative disorders. Recently, 7,8-dihydroxyflavone (7,8-DHF) has been identified as a selective TrkB agonist that crosses the blood-brain barrier after oral or intraperitoneal administration, and it enhances cued fear extinction in male rodents. However, its effects on females remain unclear. Preclinical research including both sexes is important for the development of treatment, particularly, for stress-related disorders such as post-traumatic stress disorder because such disorders are more prevalent in women. Therefore, we investigated the effects of 7,8-DHF on cued and contextual fear extinction in both male and female mice. Here we demonstrated that the administration of 7,8-DHF before each extinction session attenuated cued fear extinction in females; conversely, it enhanced cued fear extinction in males. However, administration of 7,8-DHF immediately after each extinction session did not affect cued fear extinction in either sex. Moreover, in contextual fear extinction, administration of 7,8-DHF before each extinction session did not affect fear extinction in either sex. Thus, 7,8-DHF showed sex-dependent opposite effects on cued fear extinction in mice when administered before but not immediately after each extinction session. Our results could contribute to the development of pharmacotherapy involving 7,8-DHF, particularly for stress-related disorders.

Characteristics of Cerebral Aneurysms in Japan.

The characteristics of cerebral aneurysms in Japan differ from other countries in the higher incidence of unruptured cerebral aneurysm detected by brain check-up screening, higher rupture rate of unruptured cerebral aneurysm, higher incidence of subarachnoid hemorrhage, and superior outcome after subarachnoid hemorrhage based on meta-analysis. Head shape, genetic features, environmental factors, demographics, and medical system in Japan are also different from other countries. Unruptured cerebral aneurysms are 2.8 times more likely to rupture in Japanese than western aneurysms, resulting in the highest incidence of subarachnoid hemorrhage in the world. The exact and specific mechanisms of de novo, growth, and rupture of cerebral aneurysms have not been elucidated. Investigations will contribute to the understanding of cerebral aneurysms and subarachnoid hemorrhage worldwide. Some features of cerebral aneurysm in Japan are discussed for possible research guidance in the elucidation of the predominance of subarachnoid hemorrhage in Japan.

Questionnaire Survey Regarding Prevention of Surgical Site Infection after Neurosurgery in Japan: Focus on Perioperative Management and Administration of Surgical Antibiotic Prophylaxis.

Various guidelines regarding surgical site infection (SSI) have recently been established. However, perioperative management of the wound and use of antibiotics have never been standardized completely in departments of neurosurgery in Japan. This survey investigated current perioperative management and administration of surgical antibiotic prophylaxis (SAP) and compared with guidelines intended to reduce SSI associated with neurosurgery in Japan. Questionnaires were distributed to members of the conference on Neurosurgical Techniques and Tools and the Japan Society of Aesthetic Neurosurgery via internet. The questionnaires asked about methods of perioperative management. A total of 255 members returned answers to the questionnaires. The questionnaires revealed that partial or no removal of the hair and hair shampooing at the day before surgery were performed in 96.1% and 88.1% of each institute following the World Health Organization (WHO) guidelines. Use of SAP at just before, during, and after surgery were 65.0%, 86.2%, and 63.0%, respectively. The postoperative period of use of intravenous SAP prolonged beyond 24 h in 80.0% against the recommendation of WHO. Perioperative management of wounds and use of SAP varies in institutes in Japan and some procedures were far different from the WHO guidelines. Japanese neurosurgeons should notice the prolonged SAP and comply with the WHO guidelines.

Spontaneous recovery of fear differs among early - late adolescent and adult male mice.

Adolescence is a vulnerable period for developing anxiety-related mental disorders such as post-traumatic stress disorder (PTSD), which requires a long-term course of therapy when a traumatic event has been experienced during childhood. However, the biological mechanism underlying these age-dependent characteristics remains unclear. In the present study, we used early adolescent, late adolescent and adult (4-, 8-, and 15-week old) male mice to examine age differences in fear memory, fear extinction, and spontaneous recovery of fear. We also measured the activation of extracellular signal-regulated kinase (ERK) 2 in the dorsal hippocampus (dHip) and the basolateral amygdala (BLA) following a spontaneous recovery test. Our major findings were as follows: (1) early adolescent and adult mice did not recover the fear response; only late adolescent mice recovered the fear response. (2) The ERK2 in the dHip was more activated after the spontaneous recovery test in late adolescent mice than in adult mice, and the ERK2 in the BLA was more activated after the spontaneous recovery test in adult mice than in late adolescent mice. These results suggest that there exists a unique period in which spontaneous recovery occurs and that these late adolescent behavioral signatures may be related to alteration in the ERK2 phosphorylation in the dHip and BLA.