Haloperidol-induced catalepsy is ameliorated by deep brain stimulation of the inferior colliculus.

Deep brain stimulation (DBS) has evolved as a promising alternative treatment for Parkinson's disease (PD), but the underlying mechanisms remain poorly understood. Moreover, conventional DBS protocols targeted at basal ganglia sites can turn out completely ineffective for some PD patients, warranting the search for alternative targets. The inferior colliculus (IC) is a midbrain auditory relay station involved in sensorimotor processes. High-frequency 2500 Hz electrical stimulation of the IC elicits escape behaviour and interferes with haloperidol-induced catalepsy in rats, a state reminiscent of Parkinsonian akinesia, but clinical implication is limited since the protocol is aversive. However, typical DBS stimulation frequencies range between 20-180 Hz. We therefore tested the effects of a low-frequency 30 Hz-DBS protocol on haloperidol-induced catalepsy and aversive behaviour in rats. We show that low-frequency 30 Hz-DBS targeted at the IC strongly ameliorates haloperidol-induced catalepsy without any evidence of stimulation-induced escape behaviour. Furthermore, 30 Hz-DBS of the IC produced no place avoidance in a place conditioning paradigm and induced no anxiety-related behaviour on the elevated plus maze, indicating that the protocol has no aversive or anxiogenic side effects. Our findings provide first evidence that the IC can serve as an alternative, non-conventional DBS target.

Mapping trait-like socio-affective phenotypes in rats through 50-kHz ultrasonic vocalizations.

RATIONALE: Fifty-kilohertz ultrasonic vocalizations (USV) in rats are believed to express inter-individual differences in trait-like positive affective phenotypes. Emission of 50-kHz USV can be induced by amphetamine (AMPH) to model mania-like positive affect, raising the possibility that predispositions for high 50-kHz USV production confer susceptibility to mania-like states. Such 50-kHz USV presumably express the sender's motivation for social contact and elicit social approach behavior in receivers. OBJECTIVES: We recently showed that AMPH-induced 50-kHz USV are paralleled by mania-like patterns of enhanced social approach behavior towards playback of 50-kHz USV. Here, we assessed whether these AMPH effects are dependent on trait-like inter-individual differences in 50-kHz USV production. METHODS: To this aim, we subdivided juvenile rats into those emitting low (LC) and high (HC) rates of baseline 50-kHz USV and compared them across four AMPH dosage conditions: 0.0, 0.5, 1.0, and 2.5 mg/kg. RESULTS: HC rats were considerably more susceptible to AMPH in inducing 50-kHz USV than LC rats, consistently across all examined doses. They further appeared to attribute more incentive salience to signals of rewarding social contact, as evidenced by enhanced social approach behavior towards 50-kHz USV playback, a response pattern also seen in LC rats after receiving AMPH treatment. HC but not LC rats emitted aversive 22-kHz USV following 50-kHz USV playback, indicating increased proneness to experience negative affective states if no actual social consequence followed the incentive signal. CONCLUSION: Inter-individual differences in 50-kHz USV map onto a unique trait-like socio-affective phenotype associated with enhanced emotional reactivity towards social and non-social reward, possibly conferring risk to mania-like states.

A Wireless, Bidirectional Interface for In Vivo Recording and Stimulation of Neural Activity in Freely Behaving Rats.

In vivo electrophysiology is a powerful technique to investigate the relationship between brain activity and behavior at a millisecond and micrometer scale. However, current methods mostly rely on tethered cable recordings or only use unidirectional systems, allowing either recording or stimulation of neural activity, but not at the same time or same target. Here, a new wireless, bidirectional device for simultaneous multichannel recording and stimulation of neural activity in freely behaving rats is described. The system operates through a single portable head stage that both transmits recorded activity and can be targeted in real-time for brain stimulation using a telemetry-based multichannel software. The head stage is equipped with a preamplifier and a rechargeable battery, allowing stable long-term recordings or stimulation for up to 1 h. Importantly, the head stage is compact, weighs 12 g (including battery) and thus has minimal impact on the animal´s behavioral repertoire, making the method applicable to a broad set of behavioral tasks. Moreover, the method has the major advantage that the effect of brain stimulation on neural activity and behavior can be measured simultaneously, providing a tool to assess the causal relationships between specific brain activation patterns and behavior. This feature makes the method particularly valuable for the field of deep brain stimulation, allowing precise assessment, monitoring, and adjustment of stimulation parameters during long-term behavioral experiments. The applicability of the system has been validated using the inferior colliculus as a model structure.

Effects of amphetamine on pro-social ultrasonic communication in juvenile rats: Implications for mania models.

Communication is the act of information transfer between sender and receiver. In rats, vocal communication can be studied through ultrasonic vocalizations (USV). 50-kHz USV occur in appetitive situations, most notably juvenile play, likely expressing the sender׳s positive affective state. Such appetitive 50-kHz USV serve important pro-social communicative functions and elicit social exploratory and approach behavior in the receiver. Emission of 50-kHz USV can be induced pharmacologically by the administration of psychostimulant drugs, such as amphetamine. However, it is unknown whether amphetamine affects the pro-social communicative function of 50-kHz USV in the receiver. We therefore assessed dose-response effects of amphetamine (0.0mg/kg, 0.5mg/kg, 1.0mg/kg, 2.5mg/kg, 5.0mg/kg) on pro-social ultrasonic communication on both, sender and receiver, in juvenile rats. We found an inverted U-shaped effect of amphetamine on 50-kHz USV emission, with 50-kHz USV levels being strongly enhanced by moderate doses, yet less prominent effects were seen following the highest dose. Likewise, amphetamine exerted inverted U-shaped effects on social exploratory and approach behavior induced by playback of appetitive 50-kHz USV. Social approach was enhanced by moderate amphetamine doses, but completely abolished following the highest dose. Amphetamine further dose-dependently promoted the emission of 50-kHz USV following playback of appetitive 50-kHz USV, indicating more vigorous attempts to establish social proximity. Our results support an important role of dopamine in closing a perception-and-action-loop through linking mechanisms relevant for detection and production of social vocalizations. Moreover, our approach possibly provides a new means to study mania-like aberrant social interaction and communication in animal models for bipolar disorder.

Acoustic Communication in Rats: Effects of Social Experiences on Ultrasonic Vocalizations as Socio-affective Signals.

Ultrasonic vocalizations (USV) serve important communicative functions as socio-affective signals in rats. In aversive situations, such as inter-male aggression and predator exposure, 22-kHz USV are emitted. They likely function as appeasement signals during fighting and/or as alarm calls to warn conspecifics. In appetitive situations, 50-kHz USV are uttered, most notably during social interactions, such as rough-and-tumble play and mating. It is believed that they fulfill an affiliative function as social contact calls. Social experiences or their lack, such as social isolation, can have profound impact on the emission of 22- and 50-kHz USV by the sender in later life, albeit direction and strength of observed effects vary, with time point of occurrence and duration being critical determinants. Little, however, is known about how social experiences affect the behavioral responses evoked by 22- and 50-kHz USV in the recipient. By means of our 50-kHz USV radial maze playback paradigm, we recently showed that the behavioral response elicited in the recipient is affected by post-weaning social isolation. Rats exposed to four weeks of isolation during the rough-and-tumble play period did not display social approach behavior toward 50-kHz USV but some signs of social avoidance. We further found that physical environmental enrichment providing minimal opportunities for social interactions has similar detrimental effects. Together, this indicates that social experiences can affect socio-affective communication in rodents, both at the level of sender and recipient. Deficits seen following post-weaning social isolation or physical environmental enrichment might be useful to model aspects of neurodevelopmental disorders characterized by social and communication deficits, such as autism and schizophrenia.

[Primary immunodeficiency]. / Angeborene Immundefekte.

Primary (inborn) immunodeficiency is caused by gene defects that impact both the innate and the adaptive immune system. Individuals with an immunedeficiency primarily come to medical attention with recurrent infections. Most diagnoses are first made in childhood and include cellular immunodeficiency, defects of phagocyte function and other primary immunodeficiencies. Antibody deficiencies, particularly common variable immunodeficiency (CVID) and complement defects may, however, not become manifested until adulthood. A pathological susceptibility to infection in adults is defined as more than three infections per year that require treatment with antibiotics and last longer than 4 weeks each. Clinical clues for immunodeficiency are pathological susceptibility to infections and immune dysregulation. The former is characterized by frequent and severe infections with often unusual pathogens, localization, course and/or intensity. Immune dysregulation comprises granulomas, autoimmune diseases, recurrent fever/chronic inflammation, tendency to eczema, lymphoproliferation and chronic enteritis. There are evidence-based guidelines and consensus documents for the diagnosis and treatment of primary immunodeficiencies. Therapeutic approaches depend on the nature of the immune defect and range from immunoglobulin substitution for antibody deficiencies to bone marrow transplantation for severe cellular immune defects.

Impact of a novel nutritional formula on asthma control and biomarkers of allergic airway inflammation in children.

BACKGROUND: A novel nutritional formula (NNF) enriched in eicosapentaenoic (EPA) and gamma-linolenic fatty acids and antioxidants reduces airway inflammation and improves clinical outcomes in critically ill patients, but NNF has not been evaluated in chronic inflammatory diseases such as persistent asthma. OBJECTIVE: To evaluate the efficacy, compliance, and safety of NNF in asthmatic children. METHODS: Children, 6-14 years of age, with mild to moderate persistent asthma, on as needed albuterol alone, were randomized to receive daily NNF (n=23) or control formula (n=20) for 12 weeks, with multiple assessments of asthma control, spirometry, measures of airway inflammation, formula tolerance, and adverse events. RESULTS: Daily consumption of either NNF or a control formula showed improvement in asthma-free days over time (P=0.04) but there was no difference between groups. However, the NNF group had lower exhaled nitric oxide levels compared with the control group at weeks 4, 8, and 12 (P<0.05). An overall group difference in log FEV1 PC20 (P=0.05) was found in favour of the NNF group as well. Significantly higher levels of EPA in plasma (P<0.01) and peripheral blood mononuclear cell (PBMC) (P<0.01) phospholipids in the NNF group compared with control group within 2 weeks indicated good adherence with daily NNF intake. There were no differences in adverse events for NNF vs. control after 12 weeks. CONCLUSIONS: Both NNF and control groups demonstrated improvement in asthma-free days. NNF-treated group had reduced biomarkers of disease activity. Rapid PBMC fatty acid composition changes reflected an anti-inflammatory profile. Dietary supplementation with NNF was safe and well tolerated (ClinicalTrials.gov number NCT01087710).

Health promotion capacity mapping: the Korean situation

Ten years ago the Republic of Korea enacted the National Health Promotion Act, setting the stage for health promotion action in the country. A National Health Promotion Fund was established, financed through tobacco taxes, which is now one of the largest in the world. However, despite abundant financial resources, the infrastructure needed to plan, implement, coordinate and evaluate health promotion efforts is still underdeveloped. Currently, health promotion capacity mapping efforts are emerging in Korea. Two international capacity mapping tools have been used to assess the Korean situation, namely HP-Source and the Health Promotion Capacity Profile, which was developed prior to the sixth Global Conference of Health Promotion, held in August 2005 in Bangkok, Thailand. The article summarizes and discusses the results of the capacity mapping exercise, highlights its challenges and suggest ways to improve the accuracy of health promotion capacity mapping.(AU)

rFVIIa--for acute rebleeding of a cerebral cavernous malformation.

Recurrent bleeding episodes of cavernomas especially in the brainstem can cause progressive neurological deficits. Therefore brainstem cavernomas are still a therapeutic dilemma and a treatment challenge for the neuro critical care community. We report a 39-year-old woman with spontaneous ataxia diplopia and vomiting, who has been treated for multiple intracerebral cavernomas during the last 10 years. A cerebral computed tomography (cCT) revealed a re-bleeding cavernoma in the left cerebral peduncle with consecutive obstructive hydrocephalus. As a result of the difficult anatomical location, no surgical approach was possible. As an off-label treatment, recombinant activated factor VII (rFVIIa) was administered to prevent possible further bleeding and especially further sequelae. The patient recovered well and no adverse events and especially no further bleeding of the cavernoma were observed. To our knowledge, this is the first report of the safe and successful use of rFVIIa to treat re-bleeding episodes in cavernomas. Further clinical studies are needed to specify the future potential of rFVIIa.

Unusual manifestation of acute hepatic porphyria in pregnancy.

A 22-year-old para I/gravida II developed psychiatric symptoms at 8 weeks of gestation. Subsequently neurological symptoms with seizures developed leading to a status epilepticus with continuing seizures at week 14. Anticonvulsive therapy had little effect in alleviating the seizures and the condition of the patient rapidly deteriorated. A sudden reddening of her urine lead to the diagnosis of acute hepatic porphyria confirmed by laboratory tests. After extensive discussion with the patient's family it was decided to terminate the pregnancy at week 16. Within hours after pregnancy termination the seizures stopped and the patient recovered without any neurological deficits. Acute hepatic porphyria can be triggered by pregnancy and usually presents with gastrointestinal symptoms and personality changes. In its rare neurological manifestation it can lead to untreatable convulsions which leave no option but to terminate the pregnancy.