Modelling Blood Flow and Metabolism in the Preclinical Neonatal Brain during and Following Hypoxic-Ischaemia

Hypoxia-ischaemia (HI) is a major cause of neonatal brain injury, often leading to long-term damage or death. In order to improve understanding and test new treatments, piglets are used as preclinical models for human neonates. We have extended an earlier computational model of piglet cerebral physiology for application to multimodal experimental data recorded during episodes of induced HI. The data include monitoring with near-infrared spectroscopy (NIRS) and magnetic resonance spectroscopy (MRS), and the model simulates the circulatory and metabolic processes that give rise to the measured signals. Model extensions include simulation of the carotid arterial occlusion used to induce HI, inclusion of cytoplasmic pH, and loss of metabolic function due to cell death. Model behaviour is compared to data from two piglets, one of which recovered following HI while the other did not. Behaviourally-important model parameters are identified via sensitivity analysis, and these are optimised to simulate the experimental data. For the non-recovering piglet, we investigate several state changes that might explain why some MRS and NIRS signals do not return to their baseline values following the HI insult. We discover that the model can explain this failure better when we include, among other factors such as mitochondrial uncoupling and poor cerebral blood flow restoration, the death of around 40% of the brain tissue. Copyright

In vivo pharmacological evaluations of novel olanzapine analogues in rats: a potential new avenue for the treatment of schizophrenia

Olanzapine (Olz) is one of the most effective antipsychotic drugs commonly used for treating schizophrenia. Unfortunately, Olz administration is associated with severe weight gain and metabolic disturbances. Both patients and clinicians are highly interested in the development of new antipsychotics which are as effective as atypical antipsychotics but which have a lower propensity to induce metabolic side effects. In the present study, we examined two new derivatives of Olz; OlzEt (2-ethyl-4-(4′-methylpiperazin-1′-yl)-10Hbenzo[b]thieno[2,3-e][1,4]diazepine), and OlzHomo (2-ethyl-4-(4′-methyl-1′,4′-diazepan-1′-yl)-10H-benzo[b]thieno[2,3-e] [1,4]diazepine), for their tendency to induce weight gain in rats. Weight gain and metabolic changes were measured in female Sprague Dawley rats. Animals were treated orally with Olz, OlzEt, OlzHomo (3 or 6 mg/kg/day), or vehicle (n = 8), three times daily at eight-hour intervals for 5 weeks. Furthermore, a phencyclidine (PCP)-treated rat model was used to examine the prevention of PCP-induced hyperlocomotor activity relevant for schizophrenia therapy. Male Sprague Dawley rats were pre-treated with a single dose (3 mg/kg/day) of Olz, OlzEt, OlzHomo, or vehicle (n = 12), for 2 weeks. Locomotor activity was recorded following a subcutaneous injection with either saline or PCP (10 mg/kg). Olz was found to induce weight gain, hyperphagia, visceral fat accumulation, and metabolic changes associated with reduced histamatergic H1 receptor density in the hypothalamus of treated rats. In contrast, OlzEt and OlzHomo presented promising antipsychotic effects, which did not induce weight gain or fat deposition in the treated animals. Behavioural analysis showed OlzEt to attenuate PCP-induced hyperactivity to a level similar to that of Olz; however, OlzHomo showed a lower propensity to inhibit these stereotyped behaviours. Our data suggest that the therapeutic effectiveness of OlzHomo may be delivered at a higher dose than that of Olz and OlzEt. Overall, OlzEt and OlzHomo may offer a better pharmacological profile than Olz for treating patients with schizophrenia. Clinical trials are needed to test this hypothesis

Cerebral germinoma revealed through a polydipsic polyuric syndrome in a 10-year-old girl: case report

Cerebral germinoma is rare. Although the imaging of the germinoma is very evocative, it’s very polymorphic clinical expression is at the origin of misguided diagnosis, as illustrated in our case. We report the case of a 10-year-old girl with diabetes insipidus evolving for 12 months associated with a decrease in visual acuity. Brain MRI (Magnetic Resonance Imaging) revealed a tumor process in the suprasellar region. The stereotaxic biopsy of the tumor confirmed the diagnosis of the hypothalamic germinoma, which allowed the patient to be treated by radiotherapy and chemotherapy. The incidence of cerebral germinoma, its clinical (principally diabetes insipidus) and radiological features as well as therapeutic strategies are discussed hereby

Cerebral germinoma revealed through a polydipsic polyuric syndrome in a 10-year-old girl: case report.

Cerebral germinoma is rare. Although the imaging of the germinoma is very evocative, it's very polymorphic clinical expression is at the origin of misguided diagnosis, as illustrated in our case. We report the case of a 10-year-old girl with diabetes insipidus evolving for 12 months associated with a decrease in visual acuity. Brain MRI (Magnetic Resonance Imaging) revealed a tumor process in the suprasellar region. The stereotaxic biopsy of the tumor confirmed the diagnosis of the hypothalamic germinoma, which allowed the patient to be treated by radiotherapy and chemotherapy. The incidence of cerebral germinoma, its clinical (principally diabetes insipidus) and radiological features as well as therapeutic strategies are discussed hereby

SETHI: The Flying Lab

This paper presents the new-generation test bench SETHI, developed by ONERA, the French Aerospace Lab. SETHI is a medium range platform dedicated to environmental, scientific and security applications. The first part of this paper describes the system architecture, the development state and the future capabilities. A set of recent significant results are presented: these results cover various applications, such as high spatial resolution imaging, change detection between two acquisitions, biomass measurement in the rain forest, bistatic imaging and innovative measurements, such as air-to-air imaging or circular imaging