Enhanced maternal behaviors in a mouse model of congenital blindness.

In mammals, mothering is one of the most important prosocial female behavior to promote survival, proper sensorimotor, and emotional development of the offspring. Different intrinsic and extrinsic factors can initiate and maintain these behaviors, such as hormonal, cerebral, and sensory changes. Infant cues also stimulate multisensory systems and orchestrate complex maternal responsiveness. To understand the maternal behavior driven by complex sensory interactions, it is necessary to comprehend the individual sensory systems by taking out other senses. An excellent model for investigating sensory regulation of maternal behavior is a murine model of congenital blindness, the ZRDBA mice, where both an anophthalmic and sighted mice are generated from the same litter. Therefore, this study aims to assess whether visual inputs are essential to driving maternal behaviors in mice. Maternal behaviors were assessed using three behavioral tests, including the pup retrieval test, the home cage maternal behavior test, and the maternal aggression test. Our results show that blind mothers (1) took less time to retrieve their offspring inside the nest, (2) spent more time nursing and licking their offspring in the second- and third-week postpartum, and (3) exhibited faster aggressive behaviors when exposed to an intruder male, compared to the sighted counterparts. This study provides evidence that congenitally blind mothers show more motivation to retrieve the pups, care, and protection towards their pups than sighted ones, likely due to a phenomenon of sensory compensation.

A novel capnogram analysis to guide ventilation during cardiopulmonary resuscitation: clinical and experimental observations.

BACKGROUND: Cardiopulmonary resuscitation (CPR) decreases lung volume below the functional residual capacity and can generate intrathoracic airway closure. Conversely, large insufflations can induce thoracic distension and jeopardize circulation. The capnogram (CO2 signal) obtained during continuous chest compressions can reflect intrathoracic airway closure, and we hypothesized here that it can also indicate thoracic distension. OBJECTIVES: To test whether a specific capnogram may identify thoracic distension during CPR and to assess the impact of thoracic distension on gas exchange and hemodynamics. METHODS: (1) In out-of-hospital cardiac arrest patients, we identified on capnograms three patterns: intrathoracic airway closure, thoracic distension or regular pattern. An algorithm was designed to identify them automatically. (2) To link CO2 patterns with ventilation, we conducted three experiments: (i) reproducing the CO2 patterns in human cadavers, (ii) assessing the influence of tidal volume and respiratory mechanics on thoracic distension using a mechanical lung model and (iii) exploring the impact of thoracic distension patterns on different circulation parameters during CPR on a pig model. MEASUREMENTS AND MAIN RESULTS: (1) Clinical data: 202 capnograms were collected. Intrathoracic airway closure was present in 35%, thoracic distension in 22% and regular pattern in 43%. (2) Experiments: (i) Higher insufflated volumes reproduced thoracic distension CO2 patterns in 5 cadavers. (ii) In the mechanical lung model, thoracic distension patterns were associated with higher volumes and longer time constants. (iii) In six pigs during CPR with various tidal volumes, a CO2 pattern of thoracic distension, but not tidal volume per se, was associated with a significant decrease in blood pressure and cerebral perfusion. CONCLUSIONS: During CPR, capnograms reflecting intrathoracic airway closure, thoracic distension or regular pattern can be identified. In the animal experiment, a thoracic distension pattern on the capnogram is associated with a negative impact of ventilation on blood pressure and cerebral perfusion during CPR, not predicted by tidal volume per se.

A cadaveric perfused model with antegrade arteriovenous pulsatile circulation: a new tool for teaching endovascular skills.

BACKGROUND: The benefits of using cadaveric humans in surgical training are well documented, and knowledge of the latest endovascular techniques is essential in the daily practice of vascular surgeons. Our study explores the feasibility of an affordable human cadaveric model with pulsatile and heated antegrade perfusion for reliable and reproducible endovascular or surgical simulation. METHODS: We undertook cannulation of 7 human cadavers embalmed in a saturated salt solution to create a left-to-right central perfusion with a heated solution, from the ascending thoracic aorta to the right atrium. To that end, we used surgically created carotidojugular and femorofemoral arteriovenous fistulas. Biomedical engineers designed a prototype pump for pulsatile circulation. We monitored invasive blood pressure and temperature. We used this model for training for endovascular thoracic aortic procedures and open vascular surgeries. RESULTS: The prototype pump achieved a pulsatile flow rate of 4.7 L/min. Effective cadaveric perfusion was achieved for several hours, not only with an arterioarterial pathway but also with arteriovenous circulation. The arterial pressures and in situ temperatures accurately restored vascular functions for life-like conditions. This new model made it possible to successfully perform thoracic endovascular aortic repair, subclavian artery stenting and simulation of abdominal open vascular trauma management. The saturated salt solution method and a specifically designed pump improved cost competitiveness. CONCLUSION: Endovascular simulation on human cadavers, optimized with the pulsatile and heated perfusion system, can be a dynamic adjunct for surgical training and familiarization with new devices. This reproducible teaching tool could be relevant in all surgery programs.

Effects of Congenital Blindness on Ultrasonic Vocalizations and Social Behaviors in the ZRDBA Mouse.

Mice produce ultrasonic vocalizations (USVs) at different ages and social contexts, including maternal-pup separation, social play in juveniles, social interactions, and mating in adults. The USVs' recording can be used as an index of sensory detection, internal state, and social motivation. While sensory deprivation may alter USVs' emission and some social behaviors in deaf and anosmic rodents, little is known about the effects of visual deprivation in rodents. This longitudinal study aimed to assess acoustic communication and social behaviors using a mouse model of congenital blindness. Anophthalmic and sighted mice were assayed to a series of behavioral tests at three different ages, namely, the maternal isolation-induced pup USV test and the home odor discrimination and preference test on postnatal day (PND) 7, the juvenile social test on PND 30-35, and the female urine-induced USVs and scent-marking behavior at 2-3 months. Our results evidenced that (1) at PND 7, USVs' total number between both groups was similar, all mice vocalized less during the second isolation period than the first period, and both phenotypes showed similar discrimination and preference, favoring exploration of the home bedding odor; (2) at PND 30-35, anophthalmic mice engaged less in social behaviors in the juvenile play test than sighted ones, but the number of total USVs produced is not affected; and (3) at adulthood, when exposed to a female urine spot, anophthalmic male mice displayed faster responses in terms of USVs' emission and sniffing behavior, associated with a longer time spent exploring the female urinary odor. Interestingly, acoustic behavior in the pups and adults was correlated in sighted mice only. Together, our study reveals that congenital visual deprivation had no effect on the number of USVs emitted in the pups and juveniles, but affected the USVs' emission in the adult male and impacted the social behavior in juvenile and adult mice.

Early and late visual deprivation induce hypersensitivity to mechanical and thermal noxious stimuli in the ZRDBA mouse.

BACKGROUND: Visual deprivation leads to behavioural adaptations. Early visual deprivation has greater effects on sensory systems compared with late visual deprivation. Although this has been well studied, the impact of visual deprivation on pain sensitivity has scarcely been investigated. In humans, one study indicates that pain sensitivity is increased in early, but not late-onset blindness. In animals, one study indicates that sensitivity to noxious stimulation is increased in anophthalmic mice, but the impact of late visual deprivation on sensitivity remains unknown. The aim of this behavioural study was to examine sensitivity to noxious stimulation in mice with early and late visual deprivation. We hypothesized that visual deprivation would have different effects on sensitivity to noxious stimulation depending on its onset. METHODS: In Experiment 1, mechanical and thermal sensitivity was examined in four ZRDBA mouse groups: sighted mice, anophthalmic mice, dark-reared sighted mice and adult sighted mice deprived of vision for one week. In Experiment 2, mechanical and thermal sensitivity was examined in adult sighted ZRDBA mice deprived of vision for two months. RESULTS: Anophthalmic and dark-reared mice showed mechanical and thermal hypersensitivity, while the one-week visual deprivation did not alter sensitivity. The two-month deprivation also resulted in mechanical and thermal hypersensitivity. CONCLUSIONS: These results indicate that early visual deprivation, regardless of the integrity of the visual system, induces hypersensitivity. Moreover, the present findings indicate that late visual deprivation may induce mechanical and thermal hypersensitivity, although this depends on visual deprivation duration. These results have implications for the biological significance of pain in the blind. SIGNIFICANCE: Sensory deprivation induces behavioural adaptions. For most sensory systems, the extent of these adaptations generally depends on the stage of cerebral development. In contrast, the present results indicate that for the nociceptive system, both early and late visual deprivation have similar effects. Anophthalmic, dark-reared mice and adult mice deprived of vision for two months showed thermal and mechanical hypersensitivity. This shows a clear interaction between visual and nociceptive systems and has implications for the biological significance of pain in the blind.

Anxiety and Depression Assessments in a Mouse Model of Congenital Blindness.

Previous studies have reported that visual impairment can affect the quality of life leading to mental health disorders. This study aimed to investigate associations between vision impairment, depression and anxiety using a mouse model of congenital blindness. We phenotyped 15 anophthalmic and 17 sighted adult mice in a battery of tests for anxiety and depression-like behaviors: open field test, elevated plus maze, coated test, splash test, and forced swim test. We found that: (1) Anxiety levels of the anophthalmic mice were significantly lower when compared with sighted mice, (2) Anophthalmic mice displayed more exploratory behaviors in a new environment than the sighted one, and (3) Depression levels between those groups were similar. In conclusion, this behavioral study showed that early visual deprivation lowers anxiety levels, associated with heightened exploratory activity, but does not induce depressive symptoms in a mouse model of congenital blindness, underlying several behavioral adaptations.

Structural brain plasticity induced by early blindness.

It is well established that early blindness results in behavioural adaptations. While the functional effects of visual deprivation have been well researched, anatomical studies are scarce. The aim of this study was to investigate whole brain structural plasticity in a mouse model of congenital blindness. Volumetric analyses were conducted on high-resolution MRI images and histological sections from the same brains. These morphometric measurements were compared between anophthalmic and sighted ZRDBA mice obtained by breeding ZRDCT and DBA mice. Results from MRI analyses using the Multiple Automatically Generated Templates (MAGeT) method showed smaller volume for the primary visual cortex and superior colliculi in anophthalmic compared with sighted mice. Deformation-based morphometry revealed smaller volumes within the dorsal lateral geniculate nuclei and the lateral secondary visual cortex and larger volumes within olfactory areas, piriform cortex, orbital areas and the amygdala, in anophthalmic compared with sighted mice. Histological analyses revealed a larger volume for the amygdala and smaller volume for the superior colliculi, primary visual cortex and medial secondary visual cortex, in anophthalmic compared with sighted mice. The absence of superficial visual layers of the superior colliculus and the thinner cortical layer IV of the primary and secondary visual cortices may explain the smaller volume of these areas, although this was observed in a limited sample. The present study shows large-scale brain plasticity in a mouse model of congenital blindness. In addition, the congruence of MRI and histological findings support the use of MRI to investigate structural brain plasticity in the mouse.

Perspectives on the establishment of a canadian human taphonomic facility: The experience of REST[ES].

REST[ES] is the first Canadian human taphonomic facility (HTF) dedicated to research and training relating to human decomposition in a northern temperate climate. The following paper outlines the measures taken to successfully establish, open and operate this novel Canadian HTF with particular focus on: project team and partnerships, facility location, approvals and permits, infrastructure and social acceptability. It is intended that our experience of establishing REST[ES] may serve as an example to help others with the establishment of future HTFs, thus contributing to the expansion in the global accessibility to human decomposition research and training.

Better Olfactory Performance and Larger Olfactory Bulbs in a Mouse Model of Congenital Blindness.

It is well established that early blindness results in enhancement of the remaining nonvisual sensory modalities accompanied by functional and anatomical brain plasticity. While auditory and tactile functions have been largely investigated, the results regarding olfactory functions remained less explored and less consistent. In the present study, we investigated olfactory function in blind mice using 3 tests: the buried food test, the olfactory threshold test, and the olfactory performance test. The results indicated better performance of blind mice in the buried food test and odor performance test while there was no difference in the olfactory threshold test. Using histological measurements, we also investigated if there was anatomical plasticity in the olfactory bulbs (OB), the most salient site for olfactory processing. The results indicated a larger volume of the OB driven by larger glomerular and granular layers in blind mice compared with sighted mice. Structural plasticity in the OB may underlie the enhanced olfactory performance in blind mice.

A novel ex vivo, in situ method to study the human brain through MRI and histology.

BACKGROUND: MRI-histology correlation studies of the ex vivo brain mostly employ fresh, extracted (ex situ) specimens, aldehyde fixed by immersion, which has several disadvantages for MRI scanning (e.g. deformation of the organ). A minority of studies are done ex vivo-in situ (unfixed brain), requiring an MRI scanner readily available within a few hours of the time of death. NEW METHOD: We propose a new technique, exploited by anatomists, for scanning the ex vivo brain: fixation by whole body perfusion, which implies fixation of the brain in situ. This allows scanning the brain surrounded by fluids, meninges, and skull, preserving the structural relationships of the brain in vivo. To evaluate the proposed method, five heads perfused-fixed with a saturated sodium chloride solution were employed. Three sequences were acquired on a 1.5 T MRI scanner: T1weighted, T2weighted-FLAIR, and Gradient-echo. Histology analysis included immunofluorescence for myelin basic protein and neuronal nuclei. RESULTS: All MRIs were successfully processed through a validated pipeline used with in vivo MRIs. All cases exhibited positive antigenicity for myelin and neuronal nuclei. COMPARISON WITH EXISTING METHODS: All scans registered to a standard neuroanatomical template in pseudo-Talairach space more accurately than an ex vivo-ex situ scan. The time interval to scan the ex vivo brain in situ was increased to at least 10 months. CONCLUSIONS: MRI and histology study of the ex vivo-in situ brain fixed by perfusion is an alternative approach that has important procedural and practical advantages over the two standard methods to study the ex vivo brain.

Gastric insufflation during cardiopulmonary resuscitation: A study in human cadavers.

INTRODUCTION: Bag-valve-mask ventilation is the first-line ventilation method during cardiopulmonary resuscitation (CPR). Risks include excessive volume delivery and gastric insufflation, the latter increasing the risk of pneumonia. The efficacy of ventilation can also be reduced by airway closure. We hypothesized that continuous chest compression (CC) could limit the risk of gastric insufflation compared to the recommended 30:2 interrupted CC strategy. This experimental study was performed in human "Thiel" cadavers to assess the respective impact of discontinuous vs. continuous chest compressions on gastric insufflation and ventilation during CPR. METHODS: The 30:2 interrupted CC technique was compared to continuous CC in 5 non-intubated cadavers over a 6 min-period. Flow and Airway Pressure were measured at the mask. A percutaneous gastrostomy allowed measuring the cumulative gastric insufflated volume. Two additional cadavers were equipped with esophageal and gastric catheters instead of the gastrostomy. RESULTS: For the 7 cadavers studied (4 women) median age of death was 79 [74-84] years. After 6 min of CPR, the cumulative gastric insufflation measured in 5 cadavers was markedly reduced during continuous CC compared to the interrupted CC strategy: (1.0 [0.8-4.1] vs. 5.9 [4.0-5.6] L; p < 0.05) while expired minute ventilation was slightly higher during continuous than interrupted CC (1.9 [1.4-2.8] vs. 1.6 [1.1-2.7] L/min; P < 0.05). In 2 additional cadavers, the progressive rise in baseline gastric pressure was lower during continuous CC than interrupted CC (1 and 2 cmH2O vs. 12 and 5.8 cmH2O). CONCLUSION: Continuous CC significantly reduces the volume of gas insufflated in the stomach compared to the recommended 30:2 interrupted CC strategy. Ventilation actually delivered to the lung is also slightly increased by the strategy.

Pain Hypersensitivity is Associated with Increased Amygdala Volume and c-Fos Immunoreactivity in Anophthalmic Mice.

It is well established that early blindness results in brain plasticity and behavioral changes in both humans and animals. However, only a few studies have examined the effects of blindness on pain perception. In these studies, pain hypersensitivity was reported in early, but not late, blind humans. The underlying mechanisms remain unclear, but considering its key role in pain perception and modulation, the amygdala may contribute to this pain hypersensitivity. The first aim of this study was to develop an animal model of early blindness to examine the effects of blindness on pain perception. A mouse cross was therefore developed (ZRDBA mice), in which half of the animals are born sighted and half are born anophthalmic, allowing comparisons between blind and sighted mice with the same genetic background. The second aim of the present study was to examine mechanical and thermal pain thresholds as well as pain behaviors and pain-related c-Fos immunoreactivity induced by the formalin test in the amygdalas of blind and sighted mice. Group differences in amygdala volume were also assessed histologically. Blind mice exhibited lower mechanical and thermal pain thresholds and more pain behaviors during the acute phase of the formalin test, compared with sighted mice. Moreover, pain hypersensitivity during the formalin test was associated with increased c-Fos immunoreactivity in the amygdala. Furthermore, amygdala volume was larger bilaterally in blind compared with sighted mice. These results indicate that congenitally blind mice show pain hypersensitivity like early blind individuals and suggest that this is due in part to plasticity in the amygdala.

Intrathoracic Airway Closure Impacts CO2 Signal and Delivered Ventilation during Cardiopulmonary Resuscitation.

RATIONALE: End-tidal CO2 (EtCO2) is used to monitor cardiopulmonary resuscitation (CPR), but it can be affected by intrathoracic airway closure. Chest compressions induce oscillations in expired CO2, and this could reflect variable degrees of airway patency. OBJECTIVES: To understand the impact of airway closure during CPR, and the relationship between the capnogram shape, airway closure, and delivered ventilation. METHODS: This study had three parts: 1) a clinical study analyzing capnograms after intubation in patients with out-of-hospital cardiac arrest receiving continuous chest compressions, 2) a bench model, and 3) experiments with human cadavers. For 2 and 3, a constant CO2 flow was added in the lung to simulate CO2 production. Capnograms similar to clinical recordings were obtained and different ventilator settings tested. EtCO2 was compared with alveolar CO2 (bench). An airway opening index was used to quantify chest compression-induced expired CO2 oscillations in all three clinical and experimental settings. MEASUREMENTS AND MAIN RESULTS: A total of 89 patients were analyzed (mean age, 69 ± 15 yr; 23% female; 12% of hospital admission survival): capnograms exhibited various degrees of oscillations, quantified by the opening index. CO2 value varied considerably across oscillations related to consecutive chest compressions. In bench and cadavers, similar capnograms were reproduced with different degrees of airway closure. Differences in airway patency were associated with huge changes in delivered ventilation. The opening index and delivered ventilation increased with positive end-expiratory pressure, without affecting intrathoracic pressure. Maximal EtCO2 recorded between ventilator breaths reflected alveolar CO2 (bench). CONCLUSIONS: During chest compressions, intrathoracic airway patency greatly affects the delivered ventilation. The expired CO2 signal can reflect CPR effectiveness but is also dependent on airway patency. The maximal EtCO2 recorded between consecutive ventilator breaths best reflects alveolar CO2.

A new physiological model for studying the effect of chest compression and ventilation during cardiopulmonary resuscitation: The Thiel cadaver.

BACKGROUND: Studying ventilation and intrathoracic pressure (ITP) induced by chest compressions (CC) during Cardio Pulmonary Resuscitation is challenging and important aspects such as airway closure have been mostly ignored. We hypothesized that Thiel Embalmed Cadavers could constitute an appropriate model. METHODS: We assessed respiratory mechanics and ITP during CC in 11 cadavers, and we compared it to measurements obtained in 9 out-of-hospital cardiac arrest patients and to predicted values from a bench model. An oesophageal catheter was inserted to assess chest wall compliance, and ITP variation (ΔITP). Airway pressure variation (ΔPaw) at airway opening and ΔITP generated by CC were measured at decremental positive end expiratory pressure (PEEP) to test its impact on flow and ΔPaw. The patient's data were derived from flow and airway pressure captured via the ventilator during resuscitation. RESULTS: Resistance and Compliance of the respiratory system were comparable to those of the out-of-hospital cardiac arrest patients (CRSTEC 42 ±â€¯12 vs CRSPAT 37.3 ±â€¯10.9 mL/cmH2O and ResTEC 17.5 ±â€¯7.5 vs ResPAT 20.2 ±â€¯5.3 cmH2O/L/sec), and remained stable over time. During CC, ΔITP varied from 32 ±â€¯12 cmH2O to 69 ±â€¯14 cmH2O with manual and automatic CC respectively. Transmission of ΔITP at the airway opening was significantly affected by PEEP, suggesting dynamic small airway closure at low lung volumes. This phenomenon was similarly observed in patients. CONCLUSION: Respiratory mechanics and dynamic pressures during CC of cadavers behave as predicted by a theoretical model and similarly to patients. The Thiel model is a suitable to assess ITP variations induced by ventilation during CC.

Diagnostic Accuracy of Clinical Tests for Neurogenic and Vascular Thoracic Outlet Syndrome: A Systematic Review.

OBJECTIVE: To summarize the evidence on the accuracy of clinical tests to help confirm or refute a diagnosis of thoracic outlet syndrome (TOS). METHODS: We searched 10 databases (January 1990 to February 2016) using relevant key words and medical subject headings terms. We considered diagnostic test accuracy studies comparing clinical tests for the diagnosis of TOS against a reference test. Cross-sectional, cohort, and case-control studies and randomized controlled trials were included. Risk of bias was appraised using QUADAS-2 and the Quality Appraisal of Reliability Studies checklist. We performed a qualitative synthesis of scientifically admissible studies. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guideline was used to report findings. RESULTS: A total of 3932 articles were retrieved. After removal of duplicates, 1767 articles were screened for titles and abstract, leaving 494 articles for full-text review. Ten studies met the eligibility criteria and were assessed for risk of bias, 4 of which were included in the review. None of the included studies used the same index tests when comparing with a gold standard, and quality was poor. High clinical heterogeneity and the use of different comparators prevented from pooling results. Findings suggest that prescribing magnetic resonance imaging during provocative positioning to confirm a diagnosis of TOS may be useful. However, this is associated with a high false-positive rate of venous compression. CONCLUSION: Little evidence currently supports the validity of clinical tests for the diagnosis of TOS. Future diagnostic accuracy studies should aim to use established methodological criteria and appropriate reporting guidelines to help validate clinical tests for diagnosing patients with TOS.

Sympathetic regulation and anterior cingulate cortex volume are altered in a rat model of chronic back pain.

Chronic pain is associated with autonomic disturbance. However, specific effects of chronic back pain on sympathetic regulation remain unknown. Chronic pain is also associated with structural changes in the anterior cingulate cortex (ACC), which may be linked to sympathetic dysregulation. The aim of this study was to determine whether sympathetic regulation and ACC surface and volume are affected in a rat model of chronic back pain, in which complete Freund Adjuvant (CFA) is injected in back muscles. Sympathetic regulation was assessed with renal blood flow (RBF) changes induced by electrical stimulation of a hind paw, while ACC structure was examined by measuring cortical surface and volume. RBF changes and ACC volume were compared between control rats and rats injected with CFA in back muscles segmental (T10) to renal sympathetic innervation or not (T2). In rats with CFA, chronic inflammation was observed in the affected muscles in addition to increased nuclear factor-kappa B (NF-kB) protein expression in corresponding spinal cord segments (p=0.01) as well as decreased ACC volume (p<0.05). In addition, intensity-dependent decreases in RBF during hind paw stimulation were attenuated by chronic pain at T2 (p's<0.05) and T10 (p's<0.05), but less so at T10 compared with T2 (p's<0.05). These results indicate that chronic back pain alters sympathetic functions through non-segmental mechanisms, possibly by altering descending regulatory pathways from ACC. Yet, segmental somato-sympathetic reflexes may compete with non-segmental processes depending on the back region affected by pain and according to the segmental organization of the sympathetic nervous system.

Asymmetric Direct Reciprocal Connections Between Primary Visual and Somatosensory Cortices of the Mouse.

Several studies show direct connections between primary sensory cortices involved in multisensory integration. The purpose of this study is to understand the microcircuitry of the reciprocal connections between visual and somatosensory cortices. The laminar distribution of retrogradely labeled cell bodies in V1 and in the somatosensory cortex both in (S1BF) and outside (S1) the barrel field was studied to provide layer indices in order to determine whether the connections are of feedforward, feedback or lateral type. Single axons were reconstructed and the size of their swellings was stereologically sampled. The negative layer indices in S1 and S1BF and the layer index near zero in V1 indicate that the connection from S1BF to V1 is of feedback type while the opposite is of lateral type. The greater incidence of larger axonal swellings in the projection from V1 to S1BF strongly suggests that S1BF receives a stronger driver input from V1 and that S1BF inputs to V1 have a predominant modulatory influence.

Congenital Anophthalmia and Binocular Neonatal Enucleation Differently Affect the Proteome of Primary and Secondary Visual Cortices in Mice.

In blind individuals, visually deprived occipital areas are activated by non-visual stimuli. The extent of this cross-modal activation depends on the age at onset of blindness. Cross-modal inputs have access to several anatomical pathways to reactivate deprived visual areas. Ectopic cross-modal subcortical connections have been shown in anophthalmic animals but not in animals deprived of sight at a later age. Direct and indirect cross-modal cortical connections toward visual areas could also be involved, yet the number of neurons implicated is similar between blind mice and sighted controls. Changes at the axon terminal, dendritic spine or synaptic level are therefore expected upon loss of visual inputs. Here, the proteome of V1, V2M and V2L from P0-enucleated, anophthalmic and sighted mice, sharing a common genetic background (C57BL/6J x ZRDCT/An), was investigated by 2-D DIGE and Western analyses to identify molecular adaptations to enucleation and/or anophthalmia. Few proteins were differentially expressed in enucleated or anophthalmic mice in comparison to sighted mice. The loss of sight affected three pathways: metabolism, synaptic transmission and morphogenesis. Most changes were detected in V1, followed by V2M. Overall, cross-modal adaptations could be promoted in both models of early blindness but not through the exact same molecular strategy. A lower metabolic activity observed in visual areas of blind mice suggests that even if cross-modal inputs reactivate visual areas, they could remain suboptimally processed.

Cutaneous vascularization of the femoral triangle in respect to groin incisions.

OBJECTIVE: The purpose of this anatomic study was to describe the cutaneous vascularization of the femoral triangle and its variation to evaluate the potential consequences of the classic incisions used in vascular surgery. The ultimate goal was to suggest surgical approaches that would take into account the vascularization of the inguinal region to potentially reduce the vascular lesions and wound complications at the groin. METHODS: The cutaneous arteries of the femoral triangle were studied in 11 lower limbs from 6 human embalmed cadavers. The technique included embalming of the cadavers, radiopaque latex injection, radiographs, and anatomic dissection. RESULTS: The comparison of the vascular patterns revealed that despite the high variability of the arborization of the cutaneous arteries, their distribution patterns share many characteristics. The main vascularization of the femoral triangle comes from three arteries: the superficial circumflex iliac, the superficial epigastric, and the external pudendal. The first two arteries originate generally through a common trunk that buds laterally from the femoral artery at about 1.5 cm below the inguinal ligament. This study shows that the classic vertical incision at the groin would lead to damage of the cutaneous branches that cross over the femoral artery in its proximal part (the superficial epigastric artery in 82% and the common trunk of the superficial epigastric and circumflex iliac arteries in 18%); these lesions could lead to the postsurgical disruption of the dermal blood flow. CONCLUSIONS: The classic incisions could disrupt the cutaneous blood supply and thus increase the risk of tissue necrosis around the wound, explaining the observed postsurgical complications and infections. We propose to lower the vertical incision to start 2 cm under the inguinal ligament to reduce lesions of the cutaneous arteries and the potential devascularization of the wounds.

Strain differences of the effect of enucleation and anophthalmia on the size and growth of sensory cortices in mice.

Anophthalmia is a condition in which the eye does not develop from the early embryonic period. Early blindness induces cross-modal plastic modifications in the brain such as auditory and haptic activations of the visual cortex and also leads to a greater solicitation of the somatosensory and auditory cortices. The visual cortex is activated by auditory stimuli in anophthalmic mice and activity is known to alter the growth pattern of the cerebral cortex. The size of the primary visual, auditory and somatosensory cortices and of the corresponding specific sensory thalamic nuclei were measured in intact and enucleated C57Bl/6J mice and in ZRDCT anophthalmic mice (ZRDCT/An) to evaluate the contribution of cross-modal activity on the growth of the cerebral cortex. In addition, the size of these structures were compared in intact, enucleated and anophthalmic fourth generation backcrossed hybrid C57Bl/6J×ZRDCT/An mice to parse out the effects of mouse strains and of the different visual deprivations. The visual cortex was smaller in the anophthalmic ZRDCT/An than in the intact and enucleated C57Bl/6J mice. Also the auditory cortex was larger and the somatosensory cortex smaller in the ZRDCT/An than in the intact and enucleated C57Bl/6J mice. The size differences of sensory cortices between the enucleated and anophthalmic mice were no longer present in the hybrid mice, showing specific genetic differences between C57Bl/6J and ZRDCT mice. The post natal size increase of the visual cortex was less in the enucleated than in the anophthalmic and intact hybrid mice. This suggests differences in the activity of the visual cortex between enucleated and anophthalmic mice and that early in-utero spontaneous neural activity in the visual system contributes to the shaping of functional properties of cortical networks.