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Accurate positioning of the acetabular component in total hip arthroplasty is essential to minimise the risk of dislocation and preserve the range of movement of the hip. It also affects polyethylene wear and the rate of osteolysis. Although there are many tools available to the surgeon to aid placement of the acetabular component, errors still occur, especially in version. We conducted a study of 14 cadaveric hips to investigate whether the transverse acetabular ligament can be used to align implanted cups with the correct degree of anteversion. Radiographic measurement revealed that all of the implanted cups were found to lie within the 'safe zone' for anteversion, when aligned with the ligament. [ABSTRACT FROM AUTHOR]

BACKGROUND: A knowledge and understanding of specialist anatomy, which includes radiological, laparoscopic, endoscopic and endovascular anatomy is essential for interpretation of imaging and development of procedural skills. METHODS AND MATERIALS: Medical students, specialist trainees and specialists from the London (England, UK) area were surveyed to investigate individual experiences and recommendations for: (1) timing of the introduction of specialist anatomy teaching, and (2) pedagogical methods used. Opinions relating to radiological, laparoscopic, endoscopic and endovascular anatomy were collected. Non-parametric tests were used to investigate differences in recommendations between specialist trainees and specialists. RESULTS: Two hundred and twenty-eight (53%) individuals responded to the survey. Imaging was most commonly used to learn radiological anatomy (94.5%). Procedural observation was most commonly used to learn laparoscopic (89.0%), endoscopic (87.3%) and endovascular anatomy (66.2%). Imaging was the most recommended method to learn radiological anatomy (92.1%). Procedural observation was the most recommended method for learning laparoscopic (80.0%), endoscopic (81.2%) and endovascular anatomy (42.5%). Specialist trainees and specialists recommended introduction of specialist anatomy during undergraduate training. CONCLUSION: Although the methods for specialist anatomy learning are in practice, there is no consensus on timing and structure within the anatomy curriculum. Recommendations from trainees and specialists should be considered so that the existing curriculum can be refined to maximise learning outcomes. [ABSTRACT FROM AUTHOR]

INTRODUCTION: Anatomy has been considered a core subject within the medical education curriculum. In the current setting of ever-changing diagnostic and treatment modalities, the opinion of both students and trainers is crucial for the design of an anatomy curriculum which fulfils the criteria required for safe medical practice. METHODS: Medical students, trainees and specialist trainee doctors and specialists from the London (England) area were surveyed to investigate the how curriculum changes have affected the relevance of anatomical knowledge to clinical practice and to identify recommendations for optimum teaching methods. The survey employed 5-point Likert scales and multiple-choice questions. Where the effect of training level was statistically significant (p < 0.05), post-hoc analysis was carried out using Mann-Whitney U tests. Significance levels were modified according to the Bonferroni method. RESULTS: Two hundred and twenty-eight individuals completed the survey giving a response rate of 53%. Medical students, trainees and specialists all agreed (mean Likert score 4.51, 4.79, 4.69 respectively) that knowledge of anatomy is important for medical practice. Most of the trainees (88.4%) and specialists (81.3%) used dissection to learn anatomy, but only 61.4% of medical students used this approach. Dissection was the most commonly recommended approach for learning anatomy across all the groups (41.7%-69.3%). CONCLUSIONS: Knowledge of anatomy is perceived to be important for safe clinical practice. Anatomy should be taught with other relevant system or clinical modules. Newer tools for anatomy teaching need further validation before incorporation into the curriculum. [ABSTRACT FROM AUTHOR]

Introduction: Sural nerve harvest causes paraesthesia to the lateral heel of the foot, which can debilitate those with already compromised proprioception. To circumvent this, we investigated an alternative donor nerve, branch of the lateral sural nerve complex called the sural communicating nerve (SCoNe), for its harvest and use as a vascularized nerve graft, in cadaver., Methods: The SCoNe was visualized by dissection in 15 legs from 8 human cadavers and the relationship of the SCoNe to the overall sural nerve complex was documented. The surface markings, dimensions, and the micro-neurovascular anatomy in the super-microsurgery range (up to 0.30 mm) of the SCoNe was recorded and analyzed., Results: SCoNe graft surface marking was confined within a triangle drawn between the fibular head laterally, the popliteal vertical midline medially and the tip of the lateral malleolus inferiorly. The proximal end of the SCoNe was situated at a mean intersection distance of 5 cm from both the fibular head and popliteal midline respectively. The mean length of the SCoNe was 226 ± 43 mm with a mean proximal diameter of 0.82 mm and mean distal diameter of 0.93 mm. In 53% of the cadavers, an arterial input was present in the proximal third of the SCoNe and veins were predominantly (87%) present in the distal third. In 46% and 20% of the 15 legs respectively, there was a nutrient artery and vein perfusing the SCoNe in its central segment. The external mean diameter of this artery was 0.60 ± 0.30 mm, while the vein was slightly larger with a mean diameter of 0.90 ± 0.50 mm., Discussion: SCoNe graft may preserve lateral heel sensation, compared to sural nerve harvest, pending clinical studies. It may have wide applications as a vascularized nerve graft, including being ideal as a vascularized cross-facial nerve graft because its nerve diameter is similar to the distal facial nerve branches. The accompanying artery is a good anastomotic match to the superior labial artery., (© 2023 Wiley Periodicals LLC.)

Body donation is a prosocial act providing a unique learning experience to students, ultimately impacting on patient care and science. With an increasing number of training professionals, there is an increasing need for body donors, yet little is understood about donors' beliefs and preferences. A four-center study aimed to understand donors' perceptions, 843 responses highlighted a significant relationship between completing a body donor consent form and being both an organ donor and having ever donated blood (p < 0.01). In exploring donor intentions, 69% had been considering donation for fewer than five years, 40% knew another body donor, and 27% had a family member or friend currently registered. Of those who had requested donor information packs, 97% had completed body donation consent forms. Of these, 92% had not selected any time restriction for their donation and 96% had consented to images being taken. Almost all (98%) were aware that their donation might not be accepted. Donors' motives highlighted a wish to: improve education, improve health care, advance science, and contribute to the greater good. A bimodal response was observed with body donation being used to save relatives money and inconvenience. Donors felt comfortable with their bodies being used by medical, dental, and allied health professionals; however, donors were less comfortable with their bodies being used by other groups. Only 57% were comfortable with artists, beauticians and yoga teachers using their remains. Understanding donors' motivations and decision-making process is vital to ensure resources for future and to meet any changing requirements of both donors and those studying them., (© 2022 The Authors. Anatomical Sciences Education published by Wiley Periodicals LLC on behalf of American Association for Anatomy.)

Objective: Despite the disabling deficits of motor apraxia and sensory ataxia resulting from intraoperative injury of the superior thalamocortical tracts (TCTs), region-specific electrophysiological localization is currently lacking. Herein, the authors describe a novel TCT mapping paradigm., Methods: Three patients, 1 asleep and 2 awake, underwent glioma resection affecting primarily the somatosensory cortex and underlying TCT. Stimulation was performed at the median, ulnar, and posterior tibial nerves. Parameters comprised single anodal pulses (duration 200-500 μsec, 2.1-4.7 Hz) with a current ranging from 10 to 25 mA. Recordings were captured with a bipolar stimulation probe, avoiding the classic collision technique. Positive localization sites were used to tractographically reconstruct the TCT in the third case., Results: Employing one electrophysiological paradigm, the TCT was localized subcortically in all 3 cases by using a bipolar probe, peak range of 19.6-29.2 msec, trough of 23.3-34.8 msec, stimulation range of 10-25 mA. In the last case, tractographic reconstruction of the TCT validated a highly accurate TCT localization within a specific region of the posterior limb of the internal capsule., Conclusions: The authors describe the first electrophysiological technique for intraoperative localization and protection of the TCT in both asleep and awake craniotomies with tractographic validation, while avoiding the collision paradigm. None of the above paradigms have been previously reported. More data are required to further validate this technique.

Anatomical education in the United Kingdom (UK) and Ireland has long been under scrutiny, especially since the reforms triggered in 1993 by the General Medical Council's "Tomorrow's Doctors." The aim of the current study was to investigate the state of medical student anatomy education in the UK and Ireland in 2019. In all, 39 medical schools completed the survey (100% response rate) and trained 10,093 medical students per year cohort. The teachers comprised 760 individuals, of these 143 were employed on full-time teaching contracts and 103 were employed on education and research contracts. Since a previous survey in 1999, the number of part-time staff has increased by 300%, including a significant increase in the number of anatomy demonstrators. In 2019, anatomy was predominantly taught to medical students in either a system-based or hybrid curriculum. In all, 34 medical schools (87%) used human cadavers to teach anatomy, with a total of 1,363 donors being used per annum. Gross anatomy teaching was integrated with medical imaging in 95% of medical schools, embryology in 81%, living anatomy in 78%, neuroanatomy in 73%, and histology in 68.3%. Throughout their five years of study, medical students are allocated on average 85 h of taught time for gross anatomy, 24 h for neuroanatomy, 24 h for histology, 11 h for living anatomy, and 10 for embryology. In the past 20 years, there has been an average loss of 39 h dedicated to gross anatomy teaching and a reduction in time dedicated to all other anatomy sub-disciplines., (© 2021 The Authors. Anatomical Sciences Education published by Wiley Periodicals LLC on behalf of American Association for Anatomy.)

Teaching and learning anatomy by using human cadaveric specimens has been a foundation of medical and biomedical teaching for hundreds of years. Therefore, the majority of institutions that teach topographical anatomy rely on body donation programmes to provide specimens for both undergraduate and postgraduate teaching of gross anatomy. The COVID-19 pandemic has posed an unprecedented challenge to anatomy teaching because of the suspension of donor acceptance at most institutions. This was largely due to concerns about the potential transmissibility of the SARS-CoV-2 virus and the absence of data about the ability of embalming solutions to neutralise the virus. Twenty embalming solutions commonly used in institutions in the United Kingdom and Ireland were tested for their ability to neutralise SARS-CoV-2, using an established cytotoxicity assay. All embalming solutions tested neutralised SARS-CoV-2, with the majority of solutions being effective at high-working dilutions. These results suggest that successful embalming with the tested solutions can neutralise the SARS-CoV-2 virus, thereby facilitating the safe resumption of body donation programmes and cadaveric anatomy teaching., (© 2021 The Authors. Journal of Anatomy published by John Wiley & Sons Ltd on behalf of Anatomical Society.)

The outbreak of COVID-19, resulting from widespread transmission of the SARS-CoV-2 virus, represents one of the foremost current challenges to societies across the globe, with few areas of life remaining untouched. Here, we detail the immediate impact that COVID-19 has had on the teaching and practice of anatomy, providing specific examples of the varied responses from several UK, Irish and German universities and medical schools. Alongside significant issues for, and suspension of, body donation programmes, the widespread closure of university campuses has led to challenges in delivering anatomy education via online methods, a particular problem for a practical, experience-based subject such as anatomy. We discuss the short-term consequences of COVID-19 for body donation programmes and anatomical education, and highlight issues and challenges that will need to be addressed in the medium to long term in order to restore anatomy education and practice throughout the world., (© 2020 The Authors. Journal of Anatomy published by John Wiley & Sons Ltd on behalf of Anatomical Society.)

The infrapatellar fat pad (IFP) is an extrasynovial, intracapsular, adipose body occupying the space in the knee joint between the inferior border of the patella, the femoral condyles, tibial plateau and patellar tendon. Little is known about the anatomy and normal function of the IFP, but it has been suggested to play a role in the aetiology of Anterior knee pain syndrome, including that associated with osteoarthritis. Forty-three knees from 11 male and 15 female embalmed cadavers (mean age 84 years; range 55-97 years) were investigated. The cadavers were donated and the study performed in compliance with the provisions of the UK Human Tissue Act (2004). The quadriceps tendon and the medial and lateral patellar retinacula were dissected from the patella, which was then reflected antero-distally. The IFP was carefully excised and details of its morphology and attachments to components of the knee joint were recorded, together with the presence of articular surface pathology on the patella and femoral condyles. The principal novel findings of the current study were that 81% of IFPs were attached to the superior border of the patella by supero-medial extensions and 65% were attached by supero-lateral extensions; the supero-medial extensions were larger than the supero-lateral extensions. The superior extensions of the IFP were always attached anteriorly to the patellar retinacula and in four individuals the extensions formed a full loop around the superior border of the patella. The volume of IFPs with attachments to the superior border of the patella was significantly greater (p = .007) than those without, and the IFP was attached to the medial meniscus in significantly (p = .009) more knees with IFP attachment to the superior border of the patella than those without. All IFPs were attached to the medial anterior horn of the meniscus and the medial Kaplan's ligament. Ninety-seven per cent were attached to the lateral anterior horn of the meniscus and 97% to the lateral Kaplan's ligament. The length of IFP attachment to the lateral meniscus was significantly longer (p = .004) than that to the medial meniscus. Ninety-seven per cent of IFPs were attached to the superior portion of the patellar tendon with the mean tendon attachment being 60%. Ninety-one per cent of IFPs were attached to the inferior border of the patella. Significantly fewer knees with patellar (p = .001) and femoral (p = .002) articular surface osteophytes exhibited superior IFP extensions and these extensions were significantly shorter in knees with patellar (p = .000) and femoral (p = .006) osteophytes, compared with those without. The IFP was attached to the medial meniscus in significantly fewer knees with femoral (p = .050) and patellar (p = .023) osteophytes than those without. All IFPs not attached to the anterior horn of the lateral menisci, medial Kaplan's ligament, superior patella or inferior border of the patella, were in knees with articular surface osteophytes. This relationship between IFP morphology and knee joint pathology suggests a functional role for the IFP that requires further investigation., (© 2020 Anatomical Society.)

For surgical reconstruction of the medial patello-femoral ligament (MPFL) a variety of techniques are used for fixation of the graft to the medial border of the patella. The bone bridge or V-shaped tunnel technique utilises two tunnels drilled from the medial aspect of the patella that converge centrally creating a tunnel through which the graft is threaded. This technique has advantages: it avoids hardware (bone anchors) and their associated complications, creates a broad attachment of the ligament approximating normal anatomy and the tunnel does not breach the lateral cortex of the patella reducing the risk of patella fracture. In current practice the bony tunnels are created using freehand techniques. These rely on estimation of the patella centre by the surgeon and is subject to wide variation. Additionally this technique can be inefficient, inaccurate and time consuming. To address these disadvantages a new drill-guide device was developed. A prototype drill-guide was constructed using CAD and 3D printing methods. The device was designed to allow the surgeon to accurately and efficiently drill the required v-shaped bone tunnel. To assess the efficacy of the prototype drill guide, an experiment designed to assess a group of ten surgeons with an average of 4.2 years experience performing the task of creating a v-shaped bone tunnel using a free-hand technique and the drill-guide. To determine the accuracy of the tunnel placement, the angle between drill holes, distance from centre of the patella and the amount of over-drill were measured. Procedure duration was also compared. The results revealed that the prototype drill-guide created a more accurate bone bridge than the traditional free hand method. The root mean square error for the distance from centre was 0.50 mm vs 2.12 mm and the angle between tunnels was 2.6O vs 15.9O for the prototype and traditional methods respectively. There was a mean of 8.9 mm over-drill with the traditional method, which was negated when using the guide. Surgeons using the guide were approximately 25% faster than using the traditional free-hand technique. The prototype drill-guide improved the accuracy, reduced the variability, and reduced procedure duration compared to the traditional free-hand technique.

Purpose: Gold standard recipient arteries in head and neck free flap microvascular reconstruction are currently branches of the external carotid. However, these arteries can be compromised by neck dissection or radiotherapy, resulting in 'vessel-depleted neck' and 'frozen neck' respectively. In such cases, the transverse cervical artery (TCA) may be a suitable recipient artery., Methods: The origin, course and diameter of the TCA were determined in 46 sides of neck from 23 cadavers. The distances from the origin of the TCA to the angle of the mandible, floor of the mouth and mandibular symphysis were measured to determine the pedicle length required for free flap anastomosis., Results: The TCA was present bilaterally in all subjects investigated and its course across the posterior triangle of the neck was constant between individuals. The mean distances from the origin of the TCA to the angle of mandible, floor of mouth and mandibular symphysis were 10.0, 9.2 and 12.6 cm, respectively. There were no significant differences in these distances between the left and right sides of the neck (p > 0.05 for all comparisons). The distances from the TCA origin to the angle of the mandible and floor of the mouth were significantly longer in males than in females (p = 0.004) and correlated directly with the greater height of males compared to females (p = 0.0004). The mean diameter of the TCA measured 2 cm from its origin was 2.2 mm., Conclusion: The TCA is a suitable and reliable recipient artery for free flap microvascular reconstruction, when branches of the external carotid artery are unavailable.

Core Surgical Trainees (CST) in the London (UK) Postgraduate School of Surgery receive clinical anatomy teaching in their first year of training, and, in their second year, give 30 sessions of anatomy teaching to medical and other students. This study set out to investigate the role of demonstrators from the perspective of the trainees. A focus group was convened to ascertain trainees' perspectives on demonstrating anatomy and to identify problems and improvement strategies to optimize their ability to enhance students' learning. A questionnaire was formulated and all second-year CST (n = 186-from two cohorts) in the London Postgraduate School of Surgery were invited. A total of 109 out of 186 trainees completed the questionnaire. A high percentage (98%) of trainees that completed the questionnaire responded that demonstrating was an invaluable part of their training. Sixty-two per cent responded that anatomy teaching they received in their first year of core surgical training helped them in their teaching role and 80% responded that it helped them prepare for surgical training. The study also revealed the need for improved communication between trainees and the London Postgraduate School of Surgery/Medical Schools/National Health Service Trusts to address issues such as trainees' perceived difficulty in fulfilling their teaching session requirement. The stakeholders have acknowledged and addressed the outcomes to improve the experience for both surgical trainees and students. The results indicate that anatomy demonstrating delivers important benefits to early surgical trainees, in addition to those received by the students that they teach. Clin. Anat. 31:409-416, 2018. © 2017 Wiley Periodicals, Inc., (© 2017 Wiley Periodicals, Inc.)

Data about a muscle's fibre pennation angle and physiological cross-sectional area are used in musculoskeletal modelling to estimate muscle forces, which are used to calculate joint contact forces. For the leg, muscle architecture data are derived from studies that measured pennation angle at the muscle surface, but not deep within it. Musculoskeletal models developed to estimate joint contact loads have usually been based on the mean values of pennation angle and physiological cross-sectional area. Therefore, the first aim of this study was to investigate differences between superficial and deep pennation angles within each muscle acting over the ankle and predict how differences may influence muscle forces calculated in musculoskeletal modelling. The second aim was to investigate how inter-subject variability in physiological cross-sectional area and pennation angle affects calculated ankle contact forces. Eight cadaveric legs were dissected to excise the muscles acting over the ankle. The mean surface and deep pennation angles, fibre length and physiological cross-sectional area were measured. Cluster analysis was applied to group the muscles according to their architectural characteristics. A previously validated OpenSim model was used to estimate ankle muscle forces and contact loads using architecture data from all eight limbs. The mean surface pennation angle for soleus was significantly greater (54%) than the mean deep pennation angle. Cluster analysis revealed three groups of muscles with similar architecture and function: deep plantarflexors and peroneals, superficial plantarflexors and dorsiflexors. Peak ankle contact force was predicted to occur before toe-off, with magnitude greater than five times bodyweight. Inter-specimen variability in contact force was smallest at peak force. These findings will help improve the development of experimental and computational musculoskeletal models by providing data to estimate force based on both surface and deep pennation angles. Inter-subject variability in muscle architecture affected ankle muscle and contact loads only slightly. The link between muscle architecture and function contributes to the understanding of the relationship between muscle structure and function., Competing Interests: Declaration of conflicting interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship and/or publication of this article.

The Anatomical Society's core syllabus for anatomy (2003 and later refined in 2007) set out a series of learning outcomes that an individual medical student should achieve on graduation. The core syllabus, with 182 learning outcomes grouped in body regions, referenced in the General Medical Council's Teaching Tomorrow's Doctors, was open to criticism on the grounds that the learning outcomes were generated by a relatively small group of anatomists, albeit some of whom were clinically qualified. We have therefore used a modified Delphi technique to seek a wider consensus. A Delphi panel was constructed involving 'experts' (n = 39). The revised core syllabus of 156 learning outcomes presented here is applicable to all medical programmes and may be used by curriculum planners, teachers and students alike in addressing the perennial question: 'What do I need to know ?', (© 2015 Anatomical Society.)

Introduction: Various "scarless" approaches have been described for thyroid and parathyroid surgery. The objective of the current study was to investigate patients' perception of neck scar cosmesis, its impact on quality of life (QoL) and evaluate patient preference with regards to scar location., Methods: 120 patients undergoing thyroid or parathyroid surgery were followed-up over a 5-year period (2008-2013). Validated tools were used to assess scar perception and its impact on QoL. These were evaluated against sex, age, ethnicity, operation type, histopathology, time following surgery and scar length., Results: Mean follow-up was 2.6 ± 3.8 years. One of the most common post-operative problems was scar-related (n = 18). Caucasian patients and those with benign histology expressed a lower impact on QoL (p < 0.001, p = 0.038). Sex and scar length did not significantly affect patients' perception for scar cosmesis (p > 0.05). Clinicians tended to score scar cosmesis higher than patients (p = 0.02). Most participants (75%) expressed a clear preference for an extracervical "scar-less in the neck" approach., Discussion: Scar-related issues are frequently reported following thyroid and parathyroid surgery. The negative impact, often underestimated by clinicians, is more apparent amongst Asian and Afro-Caribbean patients and can significantly impact on their QoL. This, combined with the lack of correlation between scar length and patient satisfaction, indicates the need to divert research from miniaturising neck scars to concealing them in extracervical sites., Conclusion: Patients prefer a scar-less in the neck approach when given the option. A prospective comparative study is required to compare the cervical and extracervical approaches., (Copyright © 2015 IJS Publishing Group Limited. Published by Elsevier Ltd. All rights reserved.)

Background: Transoral robotic surgery (TORS) represents a novel treatment for oropharyngeal cancer and obstructive sleep apnea. Appropriate patient selection is crucial. The purpose of this study was to investigate whether anatomic biometric measures are useful to determine the feasibility of performing TORS., Methods: Three surgeons independently evaluated feasibility in 51 soft-fix cadavers. Transoral visualization was performed with 2 retractors commonly used in TORS. Seven anthropometric parameters and the degree of mouth opening were recorded., Results: Mandibular body height, hyoid-mental length, and neck circumference demonstrated significant differences between "suboptimal" and "adequate" visualization of base of tongue and epiglottis (p < .05). Limited mouth opening was associated with suboptimal visualization. Neck circumference had the strongest influence on predicting TORS feasibility., Conclusion: Mandibular body height, hyoid-mental length, and neck circumference in conjunction with the degree of mouth opening may determine patient suitability for TORS. Clinical evaluation is essential to validate their collective usefulness., (© 2014 Wiley Periodicals, Inc.)

Changes that occur in astroglial populations of the nucleus ambiguus after recurrent (RLN) or superior (SLN) laryngeal nerve injury have hitherto not been fully characterised. In the present study, rat RLN and SLN were lesioned. After 3, 7, 14, 28 or 56 days of survival, the nucleus ambiguus was investigated by means of glial fibrillary acidic protein (GFAP) immunofluorescence or a combination of GFAP immunofluorescence and the application of retrograde tracers. GFAP immunoreactivity was significantly increased 3 days after RLN resection and it remained significantly elevated until after 28 days post injury (dpi). By 56 dpi it had returned to basal levels. In contrast, following RLN transection with repair, GFAP immunoreactivity was significantly elevated at 7 dpi and remained significantly elevated until 14 dpi. It had returned to basal levels by 28 dpi. Topographical analysis of the distribution of GFAP immunoreactivity revealed that after RLN injury, GFAP immunoreactivity was increased beyond the area of the nucleus ambiguus within which RLN motor neuron somata were located. GFAP immunoreactivity was also observed in the vicinity of neuronal somata that project into the uninjured SLN. Similarly, lesion of the SLN resulted in increased GFAP immunoreactivity around the neuronal somata projecting into it and also in the vicinity of the motor neuron somata projecting into the RLN. The increase in GFAP immunoreactivity outside of the region containing the motor neurons projecting into the injured nerve, may reflect the onset of a regenerative process attempting to compensate for impairment of one of the laryngeal nerves and may occur because of the dual innervation of the posterior cricoarytenoid muscle. This dual innervation of a very specialised muscle could provide a useful model system for studying the molecular mechanisms underlying axonal regeneration process and the results of the current study could provide the basis for studies into functional regeneration following laryngeal nerve injury, with subsequent application to humans., (© 2014 Anatomical Society.)

To investigate brain water content and ultrastructure in a rat caecal ligation and puncture (CLP) model of sepsis, adult male Wistar rats were assigned to one of the following experimental groups: CLP, Un-operated or Sham. CLP was performed under anaesthesia, Sham rats were exposed to anaesthesia, laparotomy and caecal mobilisation and Un-operated rats did not experience anaesthesia or surgery. CLP and Sham rats were sacrificed 18-20 h following recovery from surgery and Un-operated rats were sacrificed at the same time. Frontal cortex samples (CLP n = 9; Un-operated n = 10; Sham n = 8) were taken immediately post mortem and their water content determined using gravimetry. Similar samples were taken from other rats (CLP n = 8; Un-operated n = 8; Sham n = 8), processed for electron microscopy and subjected to morphometric analysis. There was significantly more brain water in CLP than Un-operated (P < 0.01) and Sham (P < 0.05) rats. Electron microscopy revealed significantly more peri-microvessel oedema in CLP than Un-operated (P < 0.001) and Sham rats (P < 0.05). Microvessel endothelial cell lumen cross-sectional area was significantly smaller in CLP than Un-operated (P < 0.001) and Sham (P < 0.05) rats and microvessel endothelial cell cross-sectional area was significantly smaller in CLP than Un-operated (P < 0.05) rats. Significantly more endothelial cell cytoplasmic area was occupied by mitochondria in CLP than Un-operated (P < 0.05) and Sham (P < 0.05) rats. However, experimental group did not affect the number of mitochondria present in endothelial cell profiles, or their cross-sectional area. Therefore, sepsis-induced cerebral oedema involves an increase in and a redistribution of brain water, together with ultrastructural changes to cerebral microvessels and adjacent tissue.

Purpose: In anatomy education, assessment may be done by written, practical or oral methods. These are used to varying degrees in UK medical schools with no consensus on the preferred approach. The purpose of this article is to highlight changes to methods of anatomical knowledge assessment utilised in medical schools since the early 1990s and to present recommended methods of assessment according to the level of medical training., Methods: Medical students, trainees and specialists in the London (UK) area were surveyed to: (1) identify methods experienced in anatomy education at medical school and (2) gather recommendations. Medical student, trainee and specialist responses were compared using non-parametric tests., Results: Two hundred and twenty-eight individuals responded to the survey giving a response rate of 53%. Subjects who graduated before 2005 were assessed significantly more frequently by practical (94.2 vs. 33.3%) and oral (84.5 vs. 13.1%) methods than those whose graduation year was 2005 or later. Subjects whose graduation year was 2005 or later were assessed significantly more frequently by written methods, such as EMQs than those whose graduation was before 2005 (68.7 vs. 25.2%). Practical examination was identified as the most recommended method of assessment in anatomy education by medical students (59.1%), trainees (all stages combined; 54.2%) and specialists (51.7%)., Conclusion: Practical assessment is recommended over written and oral methods for the assessment of anatomical knowledge. A formal evaluation of the relative benefits and limitations of available assessment tools is required.

Background & Aims: Liver failure is associated with progressive cytotoxic brain oedema (astrocyte swelling), which underlies hepatic encephalopathy (HE). Ammonia and superimposed inflammation are key synergistic factors in HE, but the mechanism(s) involved remain unknown. We aimed to determine whether aquaporin-4 (AQP4), an astrocyte endfeet bi-directional water channel, is associated with the brain oedema of HE., Method: Rats (n=60) received sham-operation (sham), 5 days hyperammonaemia-inducing diet (HD), galactosamine (GALN) induced acute liver failure (ALF), 4 weeks bile duct-ligation (BDL) induced cirrhosis, or caecal ligation and puncture (CLP), a 24h model of bacterial peritonitis. Rats from every group (except CLP) were randomised to receive intraperitoneal injections of lipopolysaccharide (LPS; 1mg/kg) or saline, prior to termination 3h later. Brain water, AQP4 protein expression (western blot) and AQP4 localisation by immunogold electron microscopy were investigated., Results: Significant hyperammonaemia was observed in saline-injected BDL (p<0.05), GALN (p<0.01), and HD (p<0.01), compared to sham rats. LPS injection did not affect arterial ammonia or plasma biochemistry in any of the treatment groups. Increased brain water was observed in saline-injected GALN (p<0.05), HD (p<0.01), and CLP (p<0.001) compared to sham rats. Brain water was numerically increased in BDL rats, but this failed to reach significance (p=0.09). LPS treatment further increased oedema significantly in all treatment groups (p<0.05, respectively). AQP4 expression was significantly increased in saline-injected BDL (p<0.05), but not other treatment groups, compared to sham rats. Membrane polarisation was maintained in BDL rats., Conclusion: The results suggest that AQP4 is not directly associated with the development of brain oedema in liver failure, hyperammonaemia, or sepsis. In cirrhosis, there is increased AQP4 protein expression, but membrane polarisation, is maintained, possibly in a compensatory attempt to limit severe brain oedema., (Copyright 2010. Published by Elsevier B.V.)

The glial cell water channel aquaporin-4 (AQP4) plays an important role in brain edema, astrocyte migration, and neuronal excitability. Zhou et al. [Zhou J, Kong H, Hua X, Xiao M, Ding J, Hu G (2008) Altered blood-brain barrier integrity in adult aquaporin-4 knockout mice. Neuroreport 19:1-5] recently reported that AQP4 deletion significantly altered blood-brain barrier integrity and glial fibrillary acidic protein (GFAP) immunoreactivity in their AQP4 null mice. Here we describe a detailed characterization of baseline brain properties in our AQP4 null mice, including gross appearance, neuronal, astrocyte and oligodendrocyte characteristics, and blood-brain barrier integrity. Gross anatomical measurements included estimates of brain and ventricle size. Neurons, astrocytes and oligodendrocytes were assessed using the neuronal nuclear marker NeuN, the astrocyte marker GFAP, and the myelin stain Luxol Fast Blue. The blood-brain barrier was studied by electron microscopy and the horseradish peroxidase extravasation technique. There were no differences in brain and ventricle sizes between wild type and AQP4 null mice, nor were there differences in the cerebral cortical density of NeuN positive nuclei, perimicrovessel and glia limitans GFAP immunoreactivity, or the thickness and myelination of the corpus callosum. The ultrastructure of microvessels in the frontal cortex and caudate nucleus of wild type vs. AQP4 null mice was indistinguishable, with features including intact endothelial tight junctions, absence of perimicrovessel astrocyte foot process edema, and absence of horseradish peroxidase extravasation. In contrast to the report by Zhou et al. (2008), our data show that AQP4 deletion in mice does not produce major structural abnormalities in the brain.

Unlabelled: Treatment of hyperammonemia and hepatic encephalopathy in cirrhosis is an unmet clinical need. The aims of this study were to determine whether L-ornithine and phenylacetate/phenylbutyrate (administered as the pro-drug phenylbutyrate) (OP) combined are synergistic and produce sustained reduction in ammonia by L-ornithine acting as a substrate for glutamine synthesis, thereby detoxifying ammonia, and the phenylacetate excreting the ornithine-derived glutamine as phenylacetylglutamine in the urine. Sprague-Dawley rats were studied 4 weeks after bile duct ligation (BDL) or sham operation. Study 1: Three hours before termination, an internal carotid sampling catheter was inserted, and intraperitoneal saline (placebo), OP, phenylbutyrate, or L-ornithine were administered after randomization. BDL was associated with significantly higher arterial ammonia and brain water and lower brain myoinositol (P < 0.01, respectively), compared with sham-operated controls, which was significantly improved in the OP-treated animals; arterial ammonia (P < 0.001), brain water (P < 0.05), brain myoinositol (P < 0.001), and urinary phenylacetylglutamine (P < 0.01). Individually, L-ornithine or phenylbutyrate were similar to the BDL group. In study 2, BDL rats were randomized to saline or OP administered intraperitoneally for 6 hours or 3, 5, or 10 days and were sacrificed between 4.5 and 5 weeks. The results showed that the administration of OP was associated with sustained reduction in arterial ammonia (P < 0.01) and brain water (P < 0.01) and markedly increased arterial glutamine (P < 0.01) and urinary excretion of phenylacetylglutamine (P < 0.01) in each of the OP treated groups., Conclusion: The results of this study provide proof of the concept that L-ornithine and phenylbutyrate/phenylacetate act synergistically to produce sustained improvement in arterial ammonia, its brain metabolism, and brain water in cirrhotic rats.

There is a transient fall in hypothalamic serotonin (5-hydroxytryptamine; 5-HT) activity in the second week post partum in male but not female rats. When this fall is masked by administration of the 5-HT(2) agonist (-) 2,5-dimethoxy-4-iodophenyl]-2-aminopropane hydrochloride [(-)DOI], over days 8-16 post partum, males are feminised in adulthood. To investigate whether the effect of 5-HT is mediated by dopamine and whether testosterone exerts its masculinising effect by reducing 5-HT and dopamine activity, male pups were treated with (-)DOI alone or together with the dopamine antagonist, haloperidol, over days 8-16 post partum, whereas females were treated with testosterone propionate on day 2 post partum. In adulthood, the volumes of the anteroventral periventricular nucleus (AVPV), sexually dimorphic nucleus of the preoptic area (SDN-POA) and arcuate nucleus (ARC) were determined, together with the number of tyrosine hydroxylase-immunoreactive (TH-ir) cells and fibres within them. The concentrations of 5-HT, dopamine and their metabolites were also measured. (-)DOI treatment increased the volume of the AVPV, decreased that of the SDN-POA and increased the number of TH-ir cells in the AVPV. These feminising effects were antagonised by concurrent haloperidol treatment. Neonatal testosterone propionate masculinised the volumes of the female AVPV and SDN-POA and reduced the number of TH-ir cells in the AVPV. Dopamine and 5-HT turnover in the AVPV was greater in female compared to male rats and neonatal testosterone propionate reduced dopamine concentration in the female AVPV. Neonatal (-)DOI had no effect on dopamine and 5-HT activity in the AVPV but increased both in the ARC. The findings that TH-ir neurone number and dopamine activity are greater in the female AVPV; the feminising effect of 5-HT is prevented by a haloperidol; and the masculinising effect of testosterone propionate is accompanied by a decrease in TH-ir neurone number and dopamine concentration in the female AVPV, suggest that dopamine is involved in hypothalamic sexual differentiation and may mediate the effect of 5-HT.

Growing evidence suggests that the arcopallium/posterior pallial amygdala plays a major role in the control of fear behaviour in birds. This brain region comprises several subdivisions, but no direct evidence is available about its functional parcellation. The aim of the present study was to investigate the relative involvement of two subdivisions of the arcopallium/posterior pallial amygdala complex in four classical tests of fear in quail: the presentation of a novel object, the 'hole-in-the-wall', 'open-field' and tonic immobility tests. Bilateral electrolytic lesions damaging the posterior part of the arcopallium/posterior pallial amygdala resulted in an increase in fear behaviour in the 'open-field' test, whereas quail with lesions damaging the anterior part of the arcopallium displayed a decrease in an 'overall fear score', compared to quail with bilateral nidopallium or sham lesions. The differential involvement of the anterior and posterior parts of the arcopallium/posterior pallial amygdala in fear behaviour is discussed in view of the known connections between the arcopallium/posterior pallial amygdala complex and brain regions considered to be limbic in nature.

Objective: To assess the surgical anatomy knowledge of gynaecological oncology (GO) trainees and to evaluate the impact of a cadaveric dissection course on postgraduate surgical training., Methods: An intensive 3-day cadaveric dissection course with illustrated lectures and supervised dissection, with a multiple-choice questionnaire (MCQ) on surgical anatomy at the beginning and end of the course was organised in the Anatomy Facility of a London Medical School. Each cadaver was embalmed with a mixture of alcohol, phenol and glycerol ("soft-preserved") rather than fixed in formalin, to more closely preserve in vivo conditions of the body. There were ten dissecting delegates, two per cadaver. The delegates dissected the abdomen and pelvis with the emphasis on surgical approaches rather than the classical descriptive anatomy approaches. Delegates also completed a course evaluation., Results: Without negative marking, the mean initial MCQ score was 57%, and final mean score 64%. With negative marking, the mean initial score was 43%, and mean final score 53%. Delegates rated the course highly, would recommend it to other trainees and considered that such a course should be incorporated into subspecialty training., Conclusion: The surgical anatomy knowledge of subspecialty trainees was weak but improved as a result of the dissection course. The most positive finding was the course evaluation. Postgraduate surgical training in GO would likely be enhanced by, and arguably requires, cadaveric dissection. "Soft-preserved" rather than formalin-fixed cadavers should be used.

Masculinization of the brain is dependent upon a perinatal surge in testosterone. It also requires a transient decrease in hypothalamic 5-HT concentration and turnover and an increase in androgen receptor (AR) expression during the second postnatal week. We have previously shown that increasing 5-HT activity over this period in male or androgenized female rats feminizes their adult behaviour and also feminizes the size of their anteroventral periventricular nucleus (AVPV) and sexually dimorphic nucleus of the preoptic area (SDN-POA). To investigate the role of 5-HT in sexual differentiation of the brain, 5-HT activity was raised over postnatal days 8-16 in male, female and androgenized female rats by daily administration of the 5-HT(2) receptor agonist (-)[2,5 dimethoxy-4-iodophenyl]-2-amino propane hydrochloride [(-)DOI]. By postnatal day 18, the size of the AVPV and SDN-POA was sexually dimorphic; their sizes were feminized by (-)DOI treatment. In the absence of (-)DOI treatment, there were significantly more AR-immunoreactive cells in the AVPV of males, and in the SDN-POA of males and androgenized females, than in those of females on postnatal day 18. (-)DOI treatment reduced the number of AR-immunoreactive cells in the AVPV and SDN-POA of males and androgenized females, but not of females, by postnatal day 18. These results suggest that 5-HT(2) receptor activation can influence sexual differentiation of the brain by controlling AR expression.

Sepsis is a major clinical challenge that is associated with encephalopathy and multi-organ dysfunction. Current therapeutic interventions are relatively ineffective and the development of novel treatments is hampered by the lack of a well-characterised animal model. Therefore, the behavioural, metabolic, physiological and histological changes resulting from 'through and through' caecal ligation and puncture (CLP) in the rat were investigated to determine its suitability as an animal model of human sepsis. CLP resulted in bacteraemia, characterised by the presence of multiple enteric species within 18-20 h. Locomotor activity was reduced within 4 h of CLP and this reduction increased with time. Pyrexia was evident 4-5 h after CLP and was followed by hypothermia beginning 17 h after intervention. CLP resulted in reduced white blood cell and platelet counts and an increased neutrophil: lymphocyte ratio within 18-20 h. It also resulted in decreased blood glucose, but not lactate levels. CLP caused histopathological changes in the cerebral cortex, liver, lungs and vascular system indicative of multi-organ dysfunction. Therefore, CLP in the rat mimics the cardinal clinical features of human sepsis and the subsequent development of multi-organ dysfunction. It appears to be the best available animal model currently available, in which to investigate the underlying pathophysiology of sepsis and identify therapeutic targets.

Measuring cytochrome c release during apoptosis provides valuable information about the nature and extent of apoptosis. Several years ago a flow cytometric method (based on selective permeabilization of the plasma membrane with digitonin) was developed that has advantages over other techniques. These experiments describe a comprehensive evaluation of that method. Apoptosis was triggered in Jurkat cells with staurosporine and then flow cytometry was used to measure three aspects of mitochondrial damage: (1) cytochrome c release (with the digitonin assay and a commercially available kit based on the same principle), using a DNA-binding dye to define cell cycle stage; (2) loss of mitochondrial cardiolipin, assessed by a decrease in 10 N-nonyl acridine orange (NAO) binding; and (3) loss of mitochondrial membrane potential, assessed by a decrease in tetramethylrhodamineethylester (TMRE) binding. The results from these three assays were compared with an antibody-based assay for cleaved caspase 3. The digitonin assay and the commercially available kit gave comparable results, showing that staurosporine caused cytochrome c release in all phases of the cell cycle and clearly defining those cells that had lost DNA due to internucleosomal DNA fragmentation. The pattern of fluorescence demonstrated that the mitochondrial apoptotic pathway was either the sole or the predominant pathway to be activated and that cytochrome c release in an individual cell was all-or-nothing. However, comparison with the other assays showed that the cytochrome c release assay underestimated the true extent of apoptosis. This was caused by the selective loss of some digitonin-treated apoptotic cells. The flow cytometry assay for cytochrome c release provides valuable information but it underestimates the percentage of apoptotic cells., (Copyright (c) 2007 International Society for Analytical Cytology.)

This review summarizes current knowledge of the genetic and hormonal control of sexual differentiation of the reproductive system, brain and brain function. While the chromosomal regulation of sexual differentiation has been understood for over 60 years, the genes involved and their actions on the reproductive system and brain are still under investigation. In 1990, the predicted testicular determining factor was shown to be the SRY gene. However, this discovery has not been followed up by elucidation of the actions of SRY, which may either stimulate a cascade of downstream genes, or inhibit a suppressor gene. The number of other genes known to be involved in sexual differentiation is increasing and the way in which they may interact is discussed. The hormonal control of sexual differentiation is well-established in rodents, in which prenatal androgens masculinize the reproductive tract and perinatal oestradiol (derived from testosterone) masculinizes the brain. In humans, genetic mutations have revealed that it is probably prenatal testosterone that masculinizes both the reproductive system and the brain. Sexual differentiation of brain structures and the way in which steroids induce this differentiation, is an active research area. The multiplicity of steroid actions, which may be specific to individual cell types, demonstrates how a single hormonal regulator, e.g. oestradiol, can exert different and even opposite actions at different sites. This complexity is enhanced by the involvement of neurotransmitters as mediators of steroid hormone actions. In view of current environmental concerns, a brief summary of the effects of endocrine disruptors on sexual differentiation is presented.

Objective: The purpose of this study was to use high-resolution MRI to evaluate the surgical anatomy of the posterior mediastinum, in particular the esophagus and its relation to the surrounding structures. The aim was to familiarize radiologists with the appearance of structures considered important in planning surgical resection of the esophagus., Materials and Methods: The thoraces of two cadavers were imaged with a 1.5-T magnet using a high-resolution T2-weighted sequence. Axial cadaveric sections of the posterior mediastinum were cut with a band saw at levels determined from the MR images, and histologic whole-mount sections of the esophagus and surrounding tissue were prepared from the cadaveric sections. The appearance of structures identified on the MR images was compared with the findings on corresponding gross anatomic and histologic whole-mount sections., Results: The MR images depicted the esophagus and structures in close anatomic relation: the pleural reflections and pericardium. The technique enabled visualization of structures to our knowledge not previously described on cross-sectional imaging: the individual layers of the esophageal wall, the thoracic duct, a connective tissue layer attaching the esophagus to the anterior wall of the aorta, and a fascial plane passing between layers of the right and left parietal pleura posterior to the esophagus., Conclusion: High-resolution MRI of the posterior mediastinum provides detailed anatomic information, delineating structures not visible on other forms of cross-sectional imaging. It can provide important information for planning surgical intervention.

Ts65Dn mice are partially trisomic for the distal region of MMU16, which is homologous with the obligate segment of HSA21 triplicated in Down syndrome (DS). Ts65Dn mice are impaired in learning tasks that require an intact hippocampus. In order to investigate the neural basis of these deficits in this mouse model of Down syndrome, quantitative light and electron microscopy were used to compare the volume densities of neurons and synapses in the hippocampus of adult Ts65Dn (n=4) and diploid mice (n=4). Neuron density was significantly lower in the CA1 of Ts65Dn compared to diploid mice (p<0.01). Total synapse density was significantly lower in the dentate gyrus (DG; p<0.001), CA3 (p<0.05) and CA1 (p<0.001) of Ts65Dn compared to diploid mice. The synapse-to-neuron ratio was significantly lower in the DG (p<0.001), CA3 (p<0.01) and CA1 (p<0.001) of Ts65Dn compared to diploid mice. When the data were broken down by synapse type, asymmetric synapse density was found to be significantly lower in the DG (p<0.001), CA3 (p<0.05) and CA1 (p<0.001) of Ts65Dn compared to diploid mice, while such a difference in symmetric synapse density was only present in the DG (p<0.01). The asymmetric synapse-to-neuron ratio was significantly lower in the DG (p<0.001), CA3 (p<0.01) and CA1 (p<0.001) of Ts65Dn compared to diploid mice, but there were no such significant differences in symmetric synapse-to-neuron ratios. These results suggest that impaired synaptic connectivity in the hippocampus of Ts65Dn mice underlies, at least in part, their cognitive impairment.

Objective: To investigate the effects of adrenergic agents on the cerebral response to sepsis., Design: Prospective, randomized, controlled, experimental animal study., Setting: Medical school research laboratories., Subjects: Twenty-eight middle white pigs (25-30 kg)., Interventions: Pigs were anesthetized, mechanically ventilated, and randomly assigned to one of the following groups: cecal peritonitis (n = 5), cecal peritonitis with dopexamine (n = 5), cecal peritonitis with dopexamine and the beta2-adrenergic receptor antagonist ICI 118,551 (n = 4), cecal peritonitis with methoxamine (n = 5), cecal peritonitis with dopexamine and methoxamine (n = 4), and sham-operated (n = 5). Sham-operated pigs were killed after laparotomy, and pigs with cecal peritonitis were killed 8 hrs after its induction. Samples of frontal cerebral cortex were taken immediately after death, processed for light and electron microscopy, and then subjected to morphometric analysis., Measurements and Main Results: There was significantly more (p <.0005) cerebral perimicrovessel edema in pigs with cecal peritonitis (80.2 microm2 +/- 5.3 sem) than in sham-operated pigs (26.2 microm2 +/- 2.7 sem) and significantly less (p <.0005) perimicrovessel edema in dopexamine-treated pigs with cecal peritonitis (39.8 microm2 +/- 5.5 sem) than in pigs with cecal peritonitis alone (80.2 microm2 +/- 5.3 sem). There was no significant difference between the amount of perimicrovessel edema in pigs with cecal peritonitis treated with dopexamine plus ICI118,551 and pigs with cecal peritonitis alone. The mean cerebral microvessel endothelial cell cross-sectional area in methoxamine-treated pigs with cecal peritonitis (26.3 microm2 +/- 2.6 sem) was significantly greater than that in pigs with cecal peritonitis alone (16.3 microm2 +/- 2.1 sem, p =.008) or in sham-operated pigs (12.3 microm2 +/- 1.3 sem, p =.0005)., Conclusions: Dopexamine protects against cerebral edema formation in sepsis by stimulation of beta2-adrenergic receptors, whereas the alpha1 adrenoceptor agonist methoxamine induces cerebral microvessel endothelial cell swelling.

Several transgenic mouse models of Alzheimer's disease (AD) have been developed that exhibit beta-amyloid (Abeta) neuropathology and behavioural deficits. However, not all studies have investigated the relationship between the development of cognitive impairment and neuropathology. Therefore, temporal changes in cognition were investigated in male and female double-mutant APPswexPS1.M146V (TASTPM) transgenic mice using an object recognition test and correlated with the development of cerebral Abeta neuropathology. Both male and female TASTPM mice exhibited similar significant cognitive impairment at 6, 8 and 10 months of age in the object recognition test, compared to wild-type littermates. There was no such cognitive impairment at 3 or 4 months of age. Quantitative immunohistochemistry using a battery of Abeta antibodies demonstrated that cerebral Abeta deposition was first apparent in 3-month-old mice, and it increased with age. The early appearance of cerebral Abeta deposits in the double-transgenic TASTPM mice supports the evidence that mutations in the PS1 gene accelerate Abeta deposition. The cerebral Abeta load was greater in female than in male TASTPM mice at all ages investigated. In the electron microscope, mature Abeta plaques comprising a fibrillar core surrounded by degenerating neurites and reactive glia were first observed in the cortex of TASTPM mice at 6 months of age, the same age at which cognitive impairment became apparent. These results suggest that the cognitive impairment in TASTPM mice is related to the disruption of neural connectivity and not simply Abeta deposition, which first occurs 3 months earlier.

In birds, as in mammals, corticotropin-releasing factor (CRF) is present in a number of extrahypothalamic brain regions, indicating that CRF may play a role in physiological and behavioral responses other than the control of adrenocorticotropin hormone release by the pituitary. To provide a foundation for investigation of the roles of CRF in the control of avian behavior, the distribution of CRF immunoreactivity was determined throughout the central nervous system of the domestic chicken (Gallus domesticus) and Japanese quail (Coturnix japonica). The distribution of CRF-immunoreactive (-ir) perikarya and fibers in the chicken and quail brain was found to be more extensive than previously reported, notably in the telencephalon. Numerous CRF-ir perikarya and fibers were present in the hyperstriatum, hippocampus, neostriatum, lobus parolfactorius, and archistriatum, as well as in the nucleus taeniae, nucleus accumbens, and bed nucleus of the stria terminalis, which exhibited the strongest immunolabeling in the telencephalon. The presence of dense populations of CRF-ir perikarya in the medial lobus parolfactorius, nucleus of the stria terminalis, and paleostriatum ventrale, apparently giving rise to CRF-ir projections to the mesencephalic reticular formation, the parabrachial/pericerulear region, and the dorsal vagal complex, suggests that these telencephalic areas may constitute part of the avian "central extended amygdala." These results have important implications for understanding the role of extrahypothalamic CRF systems in emotional responses in birds., (Copyright 2004 Wiley-Liss, Inc.)

Hypothalamic 5HT concentrations are transiently lower in male compared to female Wistar rats in the second week post partum (pp) and our previous findings have shown that pharmacologically potentiating 5HT activity over this period feminizes certain aspects of sexually differentiated behaviours in adult males and androgenized females. In order to investigate whether neonatal testosterone and 5HT interact to influence physiological and morphological brain sexual differences, females, androgenized females and males were treated with the 5HT2 agonist (-) [2,5 dimethoxy-4-iodophenyl]-2-amino propane HCl [(-) DOI], over days 8-16 pp. In androgenized females (250 microg testosterone proprionate, day 2 pp) (-) DOI prevented the delay in vaginal opening, but did not prevent the androgen-induced constant oestrus in females treated with 100 microg TP, day 2 pp. (-) DOI overcame the neonatal androgen effect in suppressing the positive feedback of ovarian steroids in a few males and androgenized females. (-) DOI had a feminizing effect on the volume of the anteroventral periventricular nucleus (normally smaller in males), by significantly increasing its volume in male and androgenized females. It also had a significant antagonistic effect on the testosterone-induced increase in the volume of the sexually dimorphic nucleus of the preoptic area in males and androgenized females. These findings support the view that raised 5HT activity in the second week of life antagonizes the masculinizing effect of neonatal testosterone.

Senile plaques composed mainly of beta-amyloid (Abeta) and neurofibrillary tangles principally composed of hyperphosphorylated tau are the major pathological features of Alzheimer's disease (AD). Despite the fact that increased expression of amyloid precursor protein (APP) and presenilin-1 (PS1) transgenes in mice lead to increased Abeta deposition in plaquelike structures in the brain, little is known about the nature and distribution of tau in these mice. Therefore the relationship between Abeta and hyperphosphorylated tau was investigated in mice carrying mutant APP and mutant PS1 transgenes using both light (LM) and electron microscopy (EM) with immunocytochemistry. LM immunocytochemistry revealed cerebral Abeta deposits to be present from 8 weeks of age, whereas hyperphosphorylated tau was not detected until 24 weeks of age, when it appeared as punctate deposits in close association with the Abeta deposits in the cortex and hippocampus. However, dystrophic neurites were not as heavily immunolabeled as they are in AD brain. EM revealed that aggregations of straight filaments (10-12 nm wide) were present in some cellular processes at the periphery of Abeta plaques in 8-month-old APP/PS1 mice. In one such mouse, single filaments and paired filaments showing a helical configuration (50-55 nm half-period, 25 nm max. width) were present in a dark, atrophic hippocampal neuron. Immunogold labeling of APP/PS1 mouse brain revealed hyperphosphorylated tau epitopes in some dystrophic neurites from 24 weeks of age that were similar to those present in AD. These results suggest that hyperphosphorylated tau appears in APP/PS1 mouse brain after the onset of Abeta deposition and although it is associated with Abeta deposits, its distribution is not identical to that in AD.

Aquaporin 1 is a water channel protein. There was little aquaporin 1 immunoreactivity in normal brain parenchyma. In astrocytomas, aquaporin 1 was expressed in microvessel endothelia and neoplastic astrocytes. In metastatic carcinomas, aquaporin 1 was present in microvessel endothelia and reactive astrocytes. Aquaporin 1 may participate in the formation of brain tumour oedema.

Septic encephalopathy is associated with breakdown of the blood-brain barrier and cerebral oedema. These features are also common properties of brain tumours. Perimicrovessel oedema, disruption of associated astrocyte end feet and neuronal injury occur in a porcine model of acute septic encephalopathy. The adrenergic system has been implicated in the inflammatory response to sepsis and may play a role in controlling blood-brain barrier permeability, since the beta2-adrenoceptor agonist dopexamine inhibits perimicrovessel oedema formation whereas the alpha1-adrenoceptor agonist methoxamine provokes it. Electron microscopy revealed tight junction opening in high-grade astrocytoma microvessels. Expression of the tight junction protein occludin is reduced in these microvessels and this reduction is inversely correlated with the degree of cerebral oedema. Normal astrocytes secrete factors that induce barrier properties in endothelial cells, whereas high-grade astrocytomas secrete vascular endothelial growth factor, which stimulates angiogenesis, down regulates occludin and increases endothelial cell permeability. The water channel protein aquaporin-4 is normally expressed in astrocyte foot processes around cerebral microvessels. Its expression is massively up-regulated in high-grade astrocytoma and around metastatic adenocarcinoma. There is a significant correlation between aquaporin-4 expression and the degree of cerebral oedema, but it is not clear whether increased aquaporin-4 expression enhances oedema formation or clearance. These results suggest that the pathophysiology of brain oedema is multifactorial, but that there may be common processes operating regardless of the aetiology.

The intrinsic neuronal organisation in the nucleus of the basal optic root of chickens was investigated. The divergent connections with various areas and the functional complexity of the nucleus require a complex intrinsic structural arrangement. Therefore, an analysis of Golgi impregnated material, ultrastructure, GABA-immunocytochemistry and biotinylated dextran-amine anterograde tracer analysis of the nucleus was carried out. In the Golgi analysis, a characteristic dendritic ramification pattern of two types of putative projection neurons was observed. These neurons form dendritic nests with their overlapping dendritic terminal sections, that develop synaptic fields with the optic fibre terminals. These synaptic fields were confirmed by electron microscopy. GABA-immunopositive terminals synapse with distinct loci of the dendritic trees of projection neurons; they may therefore play an important role in the inhibitory-modulatory system of the nucleus of the basal optic root. The GABA-immunopositive terminals derive from small and/or elongated local circuit neurons which receive retinal afferents, and from myelinated fibres afferents to the nucleus of unknown origin.

During cell death of human cultured leukocytes (Jurkat, HL-60, THP-1, U937) and freshly prepared leukocytes, we observed a greater than 100-fold increase in the affinity of apoptotic and necrotic cells for fluorescein isothiocyanate (FITC)-heparin in comparison with live cells. Binding of FITC-heparin was reversed in the presence of high ionic strength, unlabeled heparan sulfate, and heparin and pentosan polysulfate, but not in the presence of chondroitin and dermatan sulfates. During the course of cell death, the increase in the percentage of cells positive for annexin V binding correlated with the increase in the population positive for binding FITC-heparin. Confocal microscopy demonstrated that heparin binding to dead cells was restricted to 1 or 2 small domains on the surfaces of apoptotic cells and to larger, but still discrete, areas that did not localize with chromatin on ruptured necrotic cells. The heparin-binding domains originated from the nucleus and may correspond to the ribonucleoprotein-containing structures that have recently been shown to segregate within the nucleus of cells and to move onto the cell membrane. We observed that phagocytosis of dead Jurkat cells by monocyte-derived macrophages was blocked when the heparin-binding capacity of the dead cells was saturated by the addition of pentosan polysulfate. From this we concluded that the ability of dead cells to bind to heparan sulfate proteoglycans on the surfaces of macrophages may assist in phagocytic clearance.

Aquaporin-4 (AQP4) is a highly conserved water channel protein. In rats, AQP4 is expressed in astrocyte foot processes and is important in brain water homeostasis. AQP4 expression has not been investigated in non-neoplastic human brain or oedematous brain tumours, where water homeostasis is disrupted. Therefore, immunohistochemistry was used to study AQP4 expression in non-neoplastic and neoplastic human brain and blood-brain barrier permeability was assessed using contrast enhanced computed tomograms. AQP4 was present around microvessels in five specimens of non-neoplastic brain and five low grade (Daumas-Duport I or II) astrocytomas. AQP4 was massively upregulated in four and absent in one high grade (Daumas-Duport III or IV) astrocytoma. Massive upregulation of AQP4 was also found in reactive astrocytes in five metastatic adenocarcinomas. There was significant (p<0.0001) correlation between blood-brain barrier opening and upregulated AQP4 expression. Increased AQP4 expression in high grade astrocytomas and adenocarcinomas may facilitate the flow of oedema fluid.

Layer 7 is one of the retinorecipient layers of the avian optic tectum. However, little information is available about the neuronal organization of this layer and its implications for visual function. Golgi impregnation was used to investigate the retinal input to and the neuronal architecture of layer 7 of the chick optic tectum, which forms a narrow band between the two cell-dense layers 6 and 8. Anterograde tracers were also used to investigate the afferent and efferent connections of layer 7, in both the light and the electron microscope, together with GABA immunogold labelling. Three types of radial neuron were defined according to the origin and course of their axons. The perikarya of these neurons were situated in tectal layers 10-11. The principal dendrites of these radial neurons ascended to the tectal surface and gave rise to dendritic side-branches in layer 7. These dendritic side-branches received asymmetric synapses from the terminations of retinal fibre arborisations. Type 2 radial neurons, whose axons arose from the deep pole of the perikaryon or occasionally from a basal dendrite, were shown to project to the nucleus isthmi pars magnocellularis, which has previously been demonstrated to be GABAergic and to project to glomerulus-like complexes in tectal layers 4-5. In these layers, the dendritic branches of layer 13 neurons that project to the nucleus rotundus have previously been shown to receive retinal fibre input. Therefore, the retinal input to layer 7 may be able to modulate the transmission of information to the visual thalamus, by way of a feed-back loop to layers 4-5 of the tectum involving the nucleus isthmi pars magnocellularis.