Embryo survival in the oviduct not significantly influenced by major histocompatibility complex social signaling in the horse.

The major histocompatibility complex (MHC) influences sexual selection in various vertebrates. Recently, MHC-linked social signaling was also shown to influence female fertility in horses (Equus caballus) diagnosed 17 days after fertilization. However, it remained unclear at which stage the pregnancy was terminated. Here we test if MHC-linked cryptic female choice in horses happens during the first days of pregnancy, i.e., until shortly after embryonic entrance into the uterus and before fixation in the endometrium. We exposed estrous mares to one of several unrelated stallions, instrumentally inseminated them with semen of another stallion, and flushed the uterus 8 days later to test for the presence of embryos. In total 68 embryos could be collected from 97 experimental trials. This success rate of 70.1% was significantly different from the mean pregnancy rate of 45.7% observed 17 days after fertilization using the same experimental protocol but without embryo flushing. Embryo recovery rate was not significantly dependent on whether the mares had been socially exposed to an MHC-dissimilar or an MHC-similar stallion. These observations suggest that MHC-linked maternal strategies affect embryo survival mainly (or only) during the time of fixation in the uterus.

Stallion semen quality depends on major histocompatibility complex matching to teaser mare.

The major histocompatibility complex (MHC) has repeatedly been found to influence mate choice of vertebrates, with MHC-dissimilar mates typically being preferred over MHC-similar mates. We used horses (Equus caballus) to test whether MHC matching also affects male investment into ejaculates after short exposure to a female. Semen characteristics varied much among stallions. Controlling for this variance with a full-factorial within-subject experimental design, we found that a short exposure to an MHC-dissimilar mare enhanced male plasma testosterone and led to ejaculates with elevated sperm numbers as compared to exposure to an MHC-similar mare. Sperm velocity seemed not affected by the treatment. Overall genetic similarity between stallions and mares (determined from polymorphic microsatellites on 20 different chromosomes) played no significant role here. The MHC type of the teaser mare also affected characteristics of cold-stored sperm after 24 and 48 hr. As expected from ejaculate economics, sperm viability was elevated after exposure to an MHC-dissimilar mare. However, oxidative stress and the percentage of sperm with a high DNA fragmentation were mostly increased after exposure to an MHC-dissimilar mare, depending also on whether the teaser mare was in oestrous or not. We conclude that males can quickly adjust ejaculate quality relative to a female's MHC, and that this male reaction to the social environment can also affect important characteristics of cold-stored semen.

Major histocompatibility complex-linked social signalling affects female fertility.

Genes of the major histocompatibility complex (MHC) have been shown to influence social signalling and mate preferences in many species, including humans. First observations suggest that MHC signalling may also affect female fertility. To test this hypothesis, we exposed 191 female horses (Equus caballus) to either an MHC-similar or an MHC-dissimilar stimulus male around the time of ovulation and conception. A within-subject experimental design controlled for non-MHC-linked male characteristics, and instrumental insemination with semen of other males (n = 106) controlled for potential confounding effects of semen or embryo characteristics. We found that females were more likely to become pregnant if exposed to an MHC-dissimilar than to an MHC-similar male, while overall genetic distance to the stimulus males (based on microsatellite markers on 20 chromosomes) had no effect. Our results demonstrate that early pregnancy failures can be due to maternal life-history decisions (cryptic female choice) influenced by MHC-linked social signalling.

Quality of seminal fluids varies with type of stimulus at ejaculation.

The theory of ejaculate economics was mainly built around different sperm competition scenarios but also predicts that investments into ejaculates depend on female fecundity. Previous tests of this prediction focused on invertebrates and lower vertebrate, and on species with high female reproductive potential. It remains unclear whether the prediction also holds for polygynous mammals with low female reproductive potential (due to low litter size and long inter-birth intervals). We used horses (Equus caballus) to experimentally test whether semen characteristics are adjusted to the oestrous cycle of the mare a stallion is exposed to during few moments before ejaculation. We analysed 122 weekly semen samples collected from 16 stallions during exposure to either an oestrous or a dioestrous mare. Semen volume and the rate of motile sperm were higher when stallions were exposed to an oestrous than to a diestrous mare, while total sperm counts and sperm velocity remained unchanged. Sperm collected after exposure to an oestrous mare also showed reduced oxidative degeneration of cell membranes over a period of 48 hours. We conclude that stallions invest more into their seminal fluids when the chance of fertilization is elevated, and that this adjustment of ejaculate quality can happen very quickly.

MHC-correlated preferences in diestrous female horses (Equus caballus).

Genes of the major histocompatibility complex (MHC) have been shown to influence communication in many vertebrates, possibly with context-specific MHC-correlated reactions. Here we test for MHC-linked female preferences in the polygynous horse (Equus caballus) by repeatedly exposing 19 mares to a group of seven sexually experienced stallions. Each mare was tested four times during two consecutive reproductive cycles, twice during estrus and twice during diestrus. Male plasma testosterone concentrations were determined from weekly blood samples, and equine leukocyte antigen (ELA) class I and II alleles were determined serologically at the end of the experiments. Perception of male attractiveness was strongly dependent on estrous cycle: mean preference scores did not correlate for mares in diestrus and estrus and varied more during estrus than during diestrus. We found elevated female interests for MHC-dissimilar stallions, but only during diestrus, not during estrus. Female preferences were not significantly predicted by mean male testosterone plasma concentrations. However, testosterone concentrations changed during the 11 weeks of the experiment. By the end of the experiment, average testosterone concentration was significantly correlated to the average number of MHC alleles the stallions shared with the mares. We conclude that the MHC affects female preferences for stallions, but non-MHC linked male characteristics can overshadow effects of the MHC during estrus.

High interindividual and intraindividual variation of oxytocin secretion in estrous mares exposed to stallions, but no significant link to mate preferences.

Oxytocin is a hormone that may not only influence reproductive mechanisms in mammals but also their social behavior, including pair bonding. We therefore tested if the concentrations of oxytocin and other hormones reveal mate preferences of 13 mares in estrus. Each mare was first exposed to two stallions (haphazardly selected out of seven) and her behavior recorded. The mare was then returned to her box (i.e., no contact to stallions during that time). Approximately 4.5 hours later, venous blood samples were collected every minute during 30 minutes preceding exposure to one of the two previously used stallions, 6 minutes during exposure, and 30 minutes after exposure back in the mare's box. The procedure was repeated in the consecutive estrus cycle, with the difference that the mare was each exposed to the other of the two stallions during oxytocin measurements. In 20 of the 26 trials, oxytocin concentrations were significantly elevated during exposure to the stallion, without significant associations to cortisol and estradiol concentrations. We found no significant association between oxytocin secretion and preferences in the previous choice situation. While estradiol concentration showed a high repeatability over the two cycles, we found considerable intraindividual differences in oxytocin and cortisol plasma concentration among the two cycles. Partially, the variation in oxytocin concentrations could be linked to the time of ovulation, with lower oxytocin plasma concentrations in mares which ovulated later than expected. In conclusion, when teasing under experimental conditions, we found high interindividual and intraindividual variation among mares in the increase of oxytocin plasma concentrations, depending on the timing of ovulation. However, oxytocin levels seemed to be no predictor of mare preference.

Female major histocompatibility complex type affects male testosterone levels and sperm number in the horse (Equus caballus).

Odours of vertebrates often contain information about the major histocompatibility complex (MHC), and are used in kin recognition, mate choice or female investment in pregnancy. It is, however, still unclear whether MHC-linked signals can also affect male reproductive strategies. We used horses (Equus caballus) to study this question under experimental conditions. Twelve stallions were individually exposed either to an unfamiliar MHC-similar mare and then to an unfamiliar MHC-dissimilar mare, or vice versa. Each exposure lasted over a period of four weeks. Peripheral blood testosterone levels were determined weekly. Three ejaculates each were collected in the week after exposure to both mares (i.e. in the ninth week) to determine mean sperm number and sperm velocity. We found high testosterone levels when stallions were kept close to MHC-dissimilar mares and significantly lower ones when kept close to MHC-similar mares. Mean sperm number per ejaculate (but not sperm velocity) was positively correlated to mean testosterone levels and also affected by the order of presentation of mares: sperm numbers were higher if MHC-dissimilar mares were presented last than if MHC-similar mares were presented last. We conclude that MHC-linked signals influence testosterone secretion and semen characteristics, two indicators of male reproductive strategies.

Exposure to stallion accelerates the onset of mares' cyclicity.

Horses (Equus caballus) belong to the group of seasonally polyestrous mammals. Estrous cycles typically start with increasing daylight length after winter, but mares can differ greatly in the timing of onset of regular estrus cycles. Here, we test whether spatial proximity to a stallion also plays a role. Twenty-two anestrous mares were either exposed to one of two stallions (without direct physical contact) or not exposed (controls) under experimental conditions during two consecutive springs (February to April). Ovarian activity was monitored via transrectal ultrasound and stallion's direct contact time with each mare was determined three times per week for one hour each. We found that mares exposed to a stallion ovulated earlier and more often during the observational period than mares that were not exposed to stallions. Neither stallion identity nor direct contact time, mare age, body condition, size of her largest follicle at the onset of the experiment, or parasite burden significantly affected the onset of cyclicity. In conclusion, the timing of estrous cycles and cycle frequency, i.e., crucial aspects of female reproductive strategy, strongly depend on how the mares perceive their social environment. Exposing mares to the proximity of a stallion can therefore be an alternative to, for example, light programs or elaborated hormonal therapies to start the breeding season earlier and increase the number of estrous cycles in horses.

Temperature-induced sex reversal is not responsible for sex-ratio distortions in grayling Thymallus thymallus or brown trout Salmo trutta.

On the basis of the experiments carried out over various years, it was concluded that (1) grayling Thymallus thymallus and brown trout Salmo trutta are resistant to temperature-induced sex reversal at ecologically relevant temperatures, (2) environmental sex reversal is unlikely to cause the persistent sex ratio distortion observed in at least one of the study populations and (3) sex-specific tolerance of temperature-related stress may be the cause of distorted sex ratios in populations of T. thymallus or S. trutta.

Elevated resource availability sufficient to turn opportunistic into virulent fish pathogens.

There is mounting evidence that organic or inorganic enrichment of aquatic environments increases the risk of infectious diseases, with disease agents ranging from helminth parasites to fungal, bacterial, and viral pathogens. The causal link between microbial resource availability and disease risk is thought to be complex and, in the case of so-called "opportunistic pathogens," to involve additional stressors that weaken host resistance (e.g., temperature shifts or oxygen deficiencies). In contrast to this perception, our experiment shows that the link between resource levels and infection of fish embryos can be very direct: increased resource availability can transform benign microbial communities into virulent ones. We find that embryos can be harmed before further stresses (e.g., oxygen depletion) weaken them, and treatment with antibiotics and fungicides cancels the detrimental effects. The changed characteristics of symbiotic microbial communities could simply reflect density-dependent relationships or be due to a transition in life-history strategy. Our findings demonstrate that simple microhabitat changes can be sufficient to turn "opportunistic" into virulent pathogens.

The hour-glass model of corpus callosum injury.

In this retrospective study, the authors analyze the frequency, anatomical distribution and the clinical outcome of 44 patients after severe head injury, with and without lesions of the corpus callosum (CC). 44 patients with severe head injury (GCS<9 on admission), who were admitted to the intensive care unit of the Department of Neurosurgery after trauma, underwent early MR-tomography (T1, T2 and FLAIR sequences) in addition to CCT performed on admission. CC lesions were found in about 1/3 of patients with severe head injury. Posterior (splenium) lesions of the CC were three times more common than anterior lesions. Patients with CC injury were much younger compared to patients without CC injury (25 versus 34 years). The Glasgow Outcome Scale (GOS) score after six months was poor (death, persistent vegetative state, severe disability, GOS>3) in all patients with CC injury when compared to patients without CC injury (GOS<4). CC lesions are an important parameter in the assessment of severe brain trauma, hinting at the mechanism of injury as well as the outcome of patients. If a patient does not awake after blunt head injury, MRT scans (including FLAIR sequences) are indicated. A CC lesion alone is not the cause of prolonged coma but indicates a severe diffuse injury resulting in functional deorganization of the brain. The mechanisms of CC injury are discussed and a new pathophysiological model, based on the hour-glass analogy, is presented.

Early maternal investment in mice: no evidence for compatible-genes sexual selection despite hybrid vigor.

Confronting a recently mated female with a strange male can induce a pregnancy block ('Bruce effect'). The physiology of this effect is well studied, but its functional significance is still not fully understood. The 'anticipated infanticide hypothesis' suggests that the pregnancy block serves to avoid the cost of embryogenesis and giving birth to offspring that are likely to be killed by a new territory holder. Some 'compatible-genes sexual selection hypotheses' suggest that the likelihood of a pregnancy block is also dependent on the female's perception of the stud's and the stimulus male's genetic quality. We used two inbred strains of mice (C57BL/6 and BALB/c) to test all possible combinations of female strain, stud strain, and stimulus strain under experimental conditions (N(total) = 241 mated females). As predicted from previous studies, we found increased rates of pregnancy blocks if stud and stimulus strains differed, and we found evidence for hybrid vigour in offspring of between-strain mating. Despite the observed heterosis, pregnancies of within-strain matings were not more likely to be blocked than pregnancies of between-strain matings. A power analysis revealed that if we missed an existing effect (type-II error), the effect must be very small. If a female gave birth, the number and weight of newborns were not significantly influenced by the stimulus males. In conclusion, we found no support for the 'compatible-genes sexual selection hypotheses'.

Development of chronic hydrocephalus and early cranial CT findings in spontaneous intracerebral/intraventricular hemorrhage.

INTRODUCTION: Since intracerebral hemorrhage (ICH) is frequently associated with intraventricular bleeding (IVH), we sought to detect cranial computed tomography features that would indicate early on in the patient's history the development of chronic hydrocephalus with a permanent need for cerebrospinal fluid (CSF) diversion. METHODS AND MATERIALS: A total of 25 consecutive cases presenting with ICH/IVH was studied retrospectively. Outcome was assessed using the Glasgow Outcome Scale at an average of 8 months subsequently. Diagnosis of ICH/IVH and (acute) hydrocephalus was made by early cranial CT scanning employing a selection of radiological criteria according to the literature including the Evans ratio. All patients then received external ventricular drainage. Chronic hydrocephalus was diagnosed by intraventricular pressure monitoring or by cranial CT follow-up after removal of the external drainage. RESULTS: None of the radiological criteria nor the scores obtained differed between the two groups. However, the ratio of scores for IVH/ICH was higher among the patients who developed a chronic hydrocephalus. All other parameters including volume of ICH and IVH were equally distributed. Overall outcome was poor with a median GOS score of 3. CONCLUSIONS: The ICH/IVH ratio presented here can be interpreted as an individual measure of propensity to impairment of CSF circulation. Further studies on larger populations will be needed to show whether this can be employed as an early diagnostic criterion with respect to chronic hydrocephalus.

F-wave amplitudes indicate evolving spinal autonomy during spontaneous recovery of hindlimb function in rat spinal cord contusion.

STUDY DESIGN: Experimental rat model of spinal cord contusion. OBJECTIVES: To reveal the extent of spinal autonomy contributing to recovery of hindlimb function. SETTING: Experimental laboratory of a neurosurgical university department. METHODS: F-wave amplitudes as a probe for spinal cord excitability were recorded from both sciatic nerves (lumbar segments L2-L5) before and after an experimental spinal cord contusion performed in the lower thoracic spinal cord. Additionally, transcranial electrically motor evoked potentials from the hindlimbs and cerebral somatosensory potentials evoked by sciatic nerve stimulation were recorded. Clinical evaluation of hindlimb function was done regularly for survival periods of 3 and 50 days, respectively. Electrophysiological testing was performed immediately prior and after lesioning of the cord and at the endpoint of survival periods. RESULTS: Hindlimb function recovered from a mean Basso-Beattie-Bresnahan score of 5.6 on day 1 to 9.2 on day 3 (3-day-survivors) and from 7.7 to 17.2 on day 50 (50-day-survivors). This was accompanied by a significant increase of F-wave amplitudes on day 50 compared to baseline values, whereas amplitudes of somatosensory and motor-evoked potentials remained significantly depressed. CONCLUSION: Recovery of hindlimb function may at least in part be attributed to evolving spinal autonomy, which can be assessed by F-wave amplitudes.

Long-term outcome in severe traumatic brain injury is significantly influenced by brainstem involvement.

PRIMARY OBJECTIVE: To study the 1-year-outcome of 32 survivors of severe traumatic brain injury with respect to the impact of brainstem injury. RESEARCH DESIGN: Retrospective clinical study performed in a university hospital. METHODS AND PROCEDURES: Thirty-two 1-year-survivors (15 with brainstem injury present) of severe traumatic brain injury were investigated for neurological function, activities of daily living, need for care and professional ability. MAIN OUTCOMES AND RESULTS: Visual impairment, spasticity, co-ordination deficits and organic psychosis were more frequent in the group harbouring brainstem lesions. Professional ability was worse among these patients. CONCLUSION: Brainstem involvement in survivors of severe traumatic brain injury conveys a negative impact on long-term outcome.

Foreign accent syndrome following traumatic brain injury.

Foreign accent syndrome (FAS) is a very rare disorder, caused by lesions of the dominant brain hemisphere and defined as a loss of normal phonetic contrast when using the mother language. The pronunciation is perceived by native speakers as compromised by a foreign accent. This study reports about a 35-years old woman, with a FAS following a brain injury with a traumatic left temporal haemorrhage, who experienced excellent remission after 2 years.

MHC-linked susceptibility to a bacterial infection, but no MHC-linked cryptic female choice in whitefish.

Non-random gamete fusion is one of several potential cryptic female choice mechanisms that have been postulated and that may enhance the survival probability of the offspring. Previous studies have found that gamete fusion in mice is influenced by genes of the major histocompatibility complex (MHC) region. Here we test (i) whether there is MHC-dependent gamete fusion in whitefish (Coregonus sp.) and (ii) whether there is a link between the MHC and embryo susceptibility to an infection by the bacterium Pseudomonas fuorescens. We experimentally bred whitefish and reared sibships in several batches that either experienced or did not experience strong selection by P. fluorescens. We then determined the MHC class II B1 genotype of 1016 surviving larvae of several full sibships. We found no evidence for MHC-linked gamete fusion. However, in one of seven sibships we found a strong connection between the MHC class II genotype and embryo susceptibility to P. fluorescens. This connection was still significant after correcting for multiple testing. Hence, the MHC class II genotype can considerably influence embryo survival in whitefish, but gamete fusion seems to be random with respect to the MHC.

[Severe ethanol-intoxication mimics symptoms of intracranial hypertension]. / Schwere Ethanol-Intoxikation imitiert die Symptome einer intrakraniellen Drucksteigerung.

We report on a patient intoxicated with ethanol, who was found unconscious with fixed dilated pupils, deviation of eyes, absent cough and corneal reflexes, with her arms in decerebrate posture. Because of an orbital haematoma a traumatic intracranial hemorrhage with elevated intracranial pressure and compression or concussion of the brain stem was suspected. A CT-scan of the head did not reveal an intracranial mass or any radiographic signs of intracranial hypertension. Drug screening, blood gas analysis and other laboratory tests as well anamnestic data were not indicative of other intoxications or a metabolic decompensation. These unusual neurological findings were caused by a life-threatening ethanol intoxication with a blood-alcohol concentration of 700 mg/dl (151.8 mmol/l). The patient was extubated after several hours of mechanical ventilation in the intensive care unit and was discharged to a regular ward on the following day.

Intermediate and long-term outcome in traumatic brain injury is not influenced by additional multiple organ injury.

BACKGROUND: This investigation aims at evaluating the influence of additional multiple organ injury in traumatic brain injury on the outcome in terms of the ability to perform the activities of daily life, of the need of care, and of job ability. METHODS: 62 victims (male to female ratio 4 : 1; age range 15-68 years) of traumatic brain injury were studied. Group 1 (n = 24) consisted of patients who suffered from traumatic brain injury with additional multiple organ injury, group 2 (n = 38) comprised patients with isolated brain injury. Outcome was assessed at 6 and 12 months after trauma by means of different rehabilitation scores. RESULTS: After 6 as well as after 12 months, the majority of both groups were independent in the activities of daily living. Furthermore, no differences were observed concerning the need of care. Job ability was almost equal for both groups. CONCLUSION: Additional multiple organ injury does not pertain to prognosis of traumatic brain injury.

Trauma to the pontomesencephalic brainstem-a major clue to the prognosis of severe traumatic brain injury.

The objective of this study was to assess the significance of an injury to the pontomesencephalic brainstem in severe traumatic brain injury [Glasgow coma score (GCS) below 8]. Forty victims of severe traumatic brain injury with and with out compounding pathologies almost equally distributed among both groups were studied. The outcome (mean follow-up, 11.3 months) was assessed by means of the Glasgow outcome score (GOS) and of the Disability rating scale (DRS). Injury of the brainstem was detected by electrophysiological investigation (evoked potentials, brainstem reflexes) and magnetic resonance imaging (MRI) carried out early after trauma. Statistical analysis (Wilcoxon signed rank test for matched pairs) revealed a significantly worse initial GCS (median 5 versus 6), GOS (median 3 versus 4), and DRS score (median 6 versus 2) for the group with brainstem lesions than for the group without such lesions. Moreover, there was a significant accumulation of lesions of the corpus callosum, the basal ganglia, and the (para-)hippocampal area detected by MRI in the brainstem lesion group. In addition, the finding of an abnormal cortical component of the median nerve evoked somatosensory potential was significantly more frequent in the patients with brainstem injury. Traumatic brainstem lesions diagnosed by MRI a nd/or electrophysiological investigation are associated with injury to other 'deeply' situated parts ofthe brain. The finding of a brainstem lesion influences to the outcome of patients after severe traumatic brain injury.