Transport patterns and hydrodynamic context of the MERITE-HIPPOCAMPE cruise: Implications for contaminants distribution and origin.

This study aims at characterizing the hydrodynamic context and transport patterns that prevailed during the MERITE-HIPPOCAMPE cruise to assist in the interpretation of in-situ observations. The main physical attributes and structures (mesoscale eddies as well as fine-scale fronts and filaments) are analyzed based on various physical diagnostics. They were computed from satellite data and data-assimilative model outputs to describe ocean dynamics. The Northern and Algerian Currents were prominent features during the cruise while the western basin is divided by the vertically-tilted Balearic front. Temperature and salinity were used to distinguish different water masses at both surface and sub-surface. Sea-level anomalies, relative vorticity, and Okubo-Weiss parameter distributions have shown the presence of marked eddies around stations St10 and St11. Furthermore, Finite-Size Lyaponuv Exponents revealed that the former was rather located on a fine-scale filament near the edge of a cyclonic eddy while the latter was closer to the core of an anticyclone. Nearshore thermal fronts were detected with the Belkin and O'Reilly Algorithm (BOA), especially around stations St17 and St19. The potential coastal sources of contaminants were tested using Lagrangian Origin Maps (LOM), suggesting that stations St1, St2, St4, St11, and St15 were most likely influenced by coastal waters. Additionally, an atmospheric reanalysis combined with a Lagrangian dispersal model allowed for estimating wet deposition events of contaminants while tracking the fate of water masses where rainfall took place. Finally, we provide a set of explanatory quantitative and qualitative variables for future statistical analyses that aim at explaining the distribution of both chemical and biological samples collected during the cruise.

Combination of magnesium supplementation with treadmill exercise improves memory deficit in aged rats by enhancing hippocampal neurogenesis and plasticity: a functional and histological study.

This study aimed to investigate the possible ameliorative effects of co-supplementation with Mg2+ and treadmill exercise on memory deficit in aged rats. Fifty male albino rats (10 young and 40 aged rats) were divided into 5 groups (10 rats/group): young, aged sedentary, aged exercised, aged Mg2+-supplemented, and aged exercised and Mg2+-supplemented. Memory was assessed using the Y-maze and novel object recognition tests. Plasma samples were collected for measurement of C-reactive protein (CRP). Subsequently, brain malondialdehyde and catalase levels were measured. Histological and immunohistochemical analyses of the hippocampi were performed. Our results showed impaired memory in aged sedentary rats, with significantly elevated plasma CRP and brain malondialdehyde levels and decreased brain catalase. The hippocampus of aged sedentary rats showed cellular degeneration, downregulation of synaptophysin (SYP) and proliferating cell nuclear antigen (PCNA), and upregulation of glial fibrillary acidic protein (GFAP) and caspase-3. Mg2+ supplementation and/or treadmill exercise significantly improved memory tests in aged rats, which could be explained by the upregulation of hippocampal SYP and PCNA expression and downregulation of GFAP and caspase-3 expression with antioxidant and anti-inflammatory mechanisms. The combined therapy had a better effect than both treatments alone, confirming the role of Mg2+ supplementation with physical exercise in enhancing age-related memory deficit. Novelty: Magnesium supplementation with treadmill exercise improves memory deficit in aged rats. The possible mechanisms are upregulation of the hippocampal synaptophysin and PCNA, downregulation of GFAP and caspase-3, the antioxidant and anti-inflammatory mechanisms.

Radiation therapy for brain metastases.

We present the update of the recommendations of the French society for radiation oncology on radiation therapy for the management of brain metastases. It has evolved in recent years and has become more complex. As the life expectancy of patients has increased and retreatments have become more frequent, side effects must be absolutely avoided. Cognitive side effects must in particular be prevented, and the most modern radiation therapy techniques must be used systematically. New prognostic classifications specific to the primary tumour of patients, advances in imaging and radiation therapy technology and new systemic therapeutic strategies, are making treatment more relevant. Stereotactic radiation therapy has supplanted whole-brain radiation therapy both for patients with metastases in place and for those who underwent surgery. Hippocampus protection is possible with intensity-modulated radiation therapy. Its relevance in terms of cognitive functioning should be more clearly demonstrated but the requirement for its use is constantly increasing. New targeted cancer treatment therapies based on the nature of the primitive have complicated the notion of the place and timing of radiation therapy and the discussion during multidisciplinary care meeting to indicate the best sequences is becoming a challenging issue as data on the interaction between treatments remain to be documented. In the end, although aimed at patients in the palliative phase, the management of brain metastases is one of the locations for which technical reflection is the most challenging and treatment become increasingly personalized.

Inhibition of glutamatergic transmission and neuronal excitability by oxycodone in the rat hippocampal CA3 neurons.

Oxycodone, a semisynthetic opioid analgesic with actions similar to morphine, is extensively prescribed for treatment of moderate to severe acute pain. Given that glutamate plays a crucial role in mediating pain transmission, the purpose of this study was to investigate the effect of oxycodone on glutamatergic synaptic transmission in rat hippocampal CA3 area, which is associated with the modulation of nociceptive perception. Whole-cell patch-clamp recordings revealed that oxycodone effectively reduced presynaptic glutamate release, as detected by decreased frequencies of spontaneous excitatory postsynaptic currents (sEPSCs) and miniature EPSCs (mEPSCs), without eliciting significant changes in the amplitudes of sEPSCs and mEPSCs and glutamate-evoked inward currents. The inhibitory effect of oxycodone on the frequency of sEPSCs was blocked by the nonselective opioid receptor antagonist naloxone. In addition, oxycodone suppressed burst firing induced by 4-aminopyridine and tonic repetitive firing evoked by the applied depolarizing current. These results suggest that oxycodone inhibits spontaneous presynaptic glutamate release possibly by activating opioid receptors and consequently suppressing the neuronal excitability of hippocampal CA3 neurons.

[Role of astrocytic connexins in the regulation of extracellular glutamate levels: implication for the treatment of major depressive episodes]. / Rôle des connexines astrocytaires dans la régulation des taux extracellulaires de glutamate : implication pour le traitement des épisodes dépressifs majeurs.

Major depression is a psychiatric disorder relying on different neurobiological mechanisms. In particular, a hypersensitivity of the hypothalamic-pituitary-adrenal axis leading to an excess of cortisol in blood and a deficit in monoaminergic neurotransmission have been associated with mood disorders. In keeping with these mechanisms, currently available antidepressant drugs act by increasing the extracellular levels of monoamines in the synaptic cleft. Since the discovery of the rapid and long-lasting antidepressant effects of ketamine, an NMDA receptor antagonist, a growing attention in psychiatry is paid to the pharmacological tools able to attenuate glutamatergic neurotransmission. Astrocytes play an important role in the excitatory/inhibitory balance of the central nervous system through the regulation of glutamate reuptake and secretion. Interestingly, the release of this excitatory amino acid is controlled, at least in part, by plasma membrane proteins (i.e. connexins) that cluster together to form gap junctions or hemichannels. Preclinical evidence suggests that these functional entities play a critical role in emotional behaviour. After a brief overview of the literature on mood disorders and related treatments, this review describes the role of astrocytes and connexins in glutamatergic neurotransmission and major depression. Moreover, we highlight the arguments supporting the therapeutic potential of connexins blockers but also the practical difficulties to target the hemichannels while maintaining gap junctions intact.

TITLE: Rôle des connexines astrocytaires dans la régulation des taux extracellulaires de glutamate : implication pour le traitement des épisodes dépressifs majeurs. ABSTRACT: La dépression majeure est une pathologie psychiatrique reposant sur différents mécanismes neurobiologiques. Parmi ces mécanismes, on trouve une hypersensibilité de l'axe hypothalamo-hypophyso-surrénalien associée à un excès de cortisol dans le sang et un déficit de neurotransmission monoaminergique. Ainsi, l'efficacité thérapeutique des antidépresseurs actuels repose sur leur capacité à augmenter les taux extracellulaires de monoamines dans la fente synaptique. Depuis la découverte des effets antidépresseurs rapides et durables de la kétamine, un antagoniste des récepteurs NMDA, un intérêt croissant est porté sur les moyens pharmacologiques atténuant l'action du glutamate pour traiter la dépression majeure. Les astrocytes jouent un rôle prépondérant dans la balance excitation/inhibition du système nerveux central en régulant la recapture et la sécrétion du glutamate. De manière intéressante, la libération de cet acide aminé excitateur est contrôlée, du moins en partie, par des canaux membranaires regroupés au niveau de jonctions intercellulaires de type « gap ¼ ou d'hémicanaux formés par les connexines 30 et 43. Les données précliniques suggèrent que ces deux entités fonctionnelles ont des effets sur les comportements émotionnels dans différents modèles murins de dépression. Après un bref rappel sur les troubles de l'humeur et leurs traitements, cette revue de la littérature décrit le rôle des astrocytes et des connexines dans la neurotransmission glutamatergique et la dépression majeure. Les arguments avancés soulignent l'intérêt thérapeutique potentiel du blocage des connexines astrocytaires mais aussi les difficultés pratiques à cibler la fonction hémicanal sans impacter la fonction « gap ¼.

Levetiracetam induction of theta frequency oscillations in rodent hippocampus in vitro.

Levetiracetam (LEV) has been demonstrated to improve cognitive function. Hippocampal theta rhythm (4-12 Hz) is associated with a variety of cognitively related behaviors, such as exploration in both humans and animal models. We investigated the effects of LEV on the theta rhythm in the rat hippocampal CA3 in hippocampal slices in vitro. We found that LEV increased the theta power in a dose-dependent manner. The increase in theta power can be blocked by GABAA receptor (GABAAR) or NMDA receptor (NMDAR) antagonists but not by AMPA receptor antagonist, indicating the involvement of GABAAR and NMDAR in the induction of theta activity. Interestingly, LEV enhancement of theta power can be also blocked by taurine or GABA-A agonist THIP, indicating that LEV induction of theta may be related to the indirect boosting of GABA action via reduction of extrasynaptic GABAAR activation. Furthermore, the increased theta power can be partially reduced by the mACh receptor (mAChR) antagonist atropine but not by nACh receptor antagonists, suggesting that mAChR activation provides excitatory input into local network responsible for LEV-induced theta. Our study demonstrated that LEV induced a novel theta oscillation in vitro, which may have implications in the treatment of the neuronal disorders with impaired theta oscillation and cognitive function.

Displacement trauma: complex states of personal, collective and intergenerational fragmentation and their intergenerational transmission.

Originally presented at the Journal's one day conference entitled 'Displacement: Contemporary Traumatic Experience' held in London in November 2019, this paper expands on the author's theory of the implicit psychological organizing gestalt, an associated pattern of psychic functions which operate in an integrated way to simultaneously structure and organize our experience of self-cohesion and self-continuity. The gestalt, which implicitly links the formation of psychic skin, body image, cultural skin and both personal and cultural identity with place, functions as an emergent non-conscious permanent presence or background 'constant'. It develops over time and emerges out of embodied emotional experiencing with the total environment - both human and non-human. The author argues that it is the rupture of this gestalt and the disorganizing consequences of its loss which underlies the experience of displacement trauma. If disruptions in the formation of the gestalt and/or its later rupture remain unrecognized and unrepresented then the absence creates a void which can be intergenerationally transmitted. Case material is presented which describes this and which highlights the ways in which the gestalt can contribute to our understanding of collective displacement anxiety, cultural trauma and cultural complexes.

Cet article a été présenté initialement à la conférence du Journal intitulée « Le Déplacement: Une expérience traumatique contemporaine ¼ qui s'est tenue à Londres en novembre 2019. Il développe la théorie de l'auteur d'une gestalt implicite d'organisation psychologique, un schéma associé de fonctions psychiques qui opère de manière intégrée pour simultanément structurer et organiser notre expérience de cohésion de soi et de continuité de soi. Cette gestalt, qui relie implicitement la formation de la peau psychique, de l'image du corps, de la peau culturelle et de l'identité personnelle et culturelle avec le lieu, fonctionne comme une présence permanente, non-consciente et émergente, une « constante ¼ de fond: elle se développe au fil du temps et émerge à partir de l'expérience émotionnelle incarnée avec l'environnement total - humain et non-humain. L'auteur soutient que c'est la rupture de cette gestalt et les conséquences perturbantes de sa perte qui sous-tendent l'expérience du traumatisme de déplacement. Si des perturbations dans sa formation et/ou sa rupture ultérieure restent non-reconnues et non-représentées, alors l'absence crée un vide qui peut être transmis d'une génération à l'autre. L'article présente du matériel clinique décrivant ceci. Ce matériel souligne les façons dont cette gestalt peut contribuer à notre compréhension de l'angoisse collective de déplacement et du traumatisme culturel.

Presentado inicialmente en la Conferencia del Journal, titulada 'Desplazamiento: Experiencia Traumática Contemporánea' llevada a cabo en Londres, en Noviembre 2019, el presente trabajo amplía - sobre la base de la teoría de la autora sobre la Gestalt de organización psicológica implícita - un patrón asociado de funciones psíquicas, las cuales operan en un modo integrado para estructurar simultáneamente nuestra experiencia de auto-continuidad y auto-cohesión. La Gestalt, la cual implícitamente vincula la formación de la piel psíquica, la imagen corporal, la piel cultural y la identidad personal y cultural, con el lugar, funciona como una presencia permanente, emergente, no-consciente o un 'constante' contexto: se desarrolla a través del tiempo y emerge a partir de la experiencia emocional corporizada con la totalidad del medio ambiente - humano y no-humano. La autora argumenta que es la ruptura de esta Gestalt y las consecuencias desorganizadoras de su pérdida, la cual subyace a la experiencia de trauma por desplazamiento. Si las interrupciones en su formación y/o ruptura permanecen sin ser reconocidas y sin representación, entonces la ausencia crea un vacío que puede transmitirse intergeneracionalmente. Se presenta material de un caso que describe y subraya los modos en los cuales la Gestalt puede contribuir a nuestra comprensión sobre la ansiedad por desplazamiento colectivo y trauma cultural.

MicroRNA-24 alleviates isoflurane-induced neurotoxicity in rat hippocampus via attenuation of oxidative stress.

Several miRNAs have been recently suggested as potential therapeutic targets for anesthesia-related diseases. This study was carried out to explore the biological roles of miR-24 in isoflurane-treated rat hippocampal neurons. Isoflurane was used to induce neurotoxicity in a rat model. Gain- and loss-of-function of miR-24 was performed, and the size and Ca2+ permeability of mitochondria, as well as cell proliferation and apoptosis, and levels of oxidative-stress-related factors were measured both in vivo and in vitro. Dual luciferase reporter gene assays were used to identify the target relationship between miR-24 and p27kip1. In this study, isoflurane treatment decreased miR-24 expression, after which, levels of neuron apoptosis and oxidative-stress-related factors were elevated and neuron viability was reduced. Over-expression of miR-24 inhibited oxidative damage and neuronal apoptosis in hippocampal tissues, and suppressed the size and Ca2+ permeability of mitochondria of hippocampal neurons. miR-24 enhanced the viability of rat hippocampal neurons by targeting p27kip1. To conclude, this study demonstrated that miR-24 attenuates isoflurane-induced neurotoxicity in rat hippocampus via its antioxidative properties and inhibiting p27kip1 expression.

Nandrolone administration abolishes hippocampal fEPSP-PS potentiation and passive avoidance learning of adolescent male rats.

Despite the chronic effects of nandrolone decanoate (ND), the acute effects of ND on passive avoidance learning (PAL) and memory and its mechanism have not been investigated. This research examines the acute effect of ND on PAL, CA1 synaptic plasticity, testosterone and corticosterone serum levels, and the role of androgenic receptors (ARs). Adolescent male rats were treated with ND, 30 min before training and retention and after training test. AR antagonist was applied 15 min before ND. Hippocampal slices were perfused by ND. ND administration had an inverted U-shape effect on acquisition of PAL and on testosterone and corticosterone serum levels. The consolidation was only affected by high dose of ND. ND significantly decreased the retention of PAL across all doses. The magnitude of field excitatory postsynaptic potential long term potentiation was lower than that of control slices. In addition, an attenuation of field excitatory postsynaptic potential population spike coupling was also observed. Nilutamide could nullify the ND impairment effect. We concluded although a single dose of ND could affect all stages of PAL, its effects were more potent on retrieval, possibly arising from the acute effect of ND on the alterations of CA1 synaptic plasticity. In addition, ND may induce its effects directly through ARs and indirectly through plasma testosterone and corticosterone.

Acute exercise induced BDNF-TrkB signalling is intact in the prefrontal cortex of obese, glucose-intolerant male mice.

Obesity and glucose intolerance have been directly implicated in the pathology of Alzheimer's disease. It is thought that diet-induced obesity causes a reduction in neuronal plasticity through a reduction in the neurotrophin: brain-derived neurotrophic factor (BDNF). Previous work has demonstrated that acute exercise in healthy lean animals increases BDNF-TrkB signalling in the brain. However, if this effect is intact in a state of obesity remains unknown. The purpose of this study is to determine the effects of a single bout of exercise on BDNF-TrkB signalling in the prefrontal cortex and hippocampus from obese glucose intolerant mice. Male C57BL/6 mice were fed a low-fat diet (10% kcals from lard) or a high-fat diet (HFD, 60% kcals from lard) for 7 weeks. A subset of HFD mice underwent an acute bout of exercise (treadmill running: 15 m/min, 5% incline, 120 min) followed by a recovery period of 2 h, after which point the prefrontal cortex and hippocampus were collected. The HFD increased body mass and glucose intolerance (p < 0.05). Prefrontal cortex from HFD mice demonstrated lower BDNF protein content, reduced phosphorylation of the BDNF receptor (TrkB), and its downstream effector cAMP response element-binding protein (CREB), as well as PGC-1α and ERα) protein content (p < 0.05). Two hours following the acute exercise bout, TrkB and CREB phosphorylation as well as PGC-1α and ER-α protein content were recovered (p < 0.05). Our findings demonstrate for the first time that an acute bout of exercise can recover BDNF-TrkB signalling in the prefrontal cortex of obese mice.

Hippocampal sparing in stereotactic radiotherapy for brain metastases: To contour or not contour the hippocampus?

PURPOSE: The aim of our study was to evaluate hippocampal irradiation in patients treated with fractionated stereotactic brain radiotherapy. PATIENTS AND METHODS: Retrospective hippocampal dosimetric analysis performed on 22 patients with one to four brain metastases treated with fractionated stereotactic radiotherapy using volumetric intensity-modulated arc therapy. Original plans did not include hippocampus as avoidance structure in optimization criteria; hippocampus was retrospectively delineated on magnetic resonance coregistered with planning CT and using as reference the RTOG 0933 atlas. Hippocampus was defined both as a single and as pair organ. Constraints analysed were: Dmax<16Gy, D40%<7.3Gy, D100%=Dmin<9Gy. Assuming a α/ß ratio of 2Gy, biologically equivalent dose in 2Gy fractions was calculated. Hippocampal-sparing plans were developed in cases where hippocampal constraints were not respected in the original plan. RESULTS: Among constraints analysed Dmax and D40% have been exceeded in ten out of 22 cases. The constraints were not respected in patients with more than one metastatic lesion and in three patients with only one lesion. Considering all exceeded constraints values in non-hippocampal sparing plans, the 50% of them was respected after replanning. No significant differences were found among conformity and homogeneity index between non-hippocampal sparing and hippocampal sparing plans. CONCLUSION: Volumetric intensity-modulated arc therapy hippocampal sparing plans significantly decreases dose to hippocampus assuring an equal target coverage and organs at risk avoiding.

Electrically evoked local muscle contractions cause an increase in hippocampal BDNF.

High-intensity exercise has recently been shown to cause an increase in brain-derived neurotropic factor (BDNF) in the hippocampus. Some studies have suggested that myokines secreted from contracting skeletal muscle, such as irisin (one of the truncated form of fibronectin type III domain-containing protein 5 (FNDC5)), play important roles in this process. Thus, we hypothesized that locally evoked muscle contractions may cause an increase of BDNF in the hippocampus through some afferent mechanisms. Under anesthesia, Sprague-Dawley rats were fixed on a custom-made dynamometer and their triceps surae muscles were made to maximally contract via delivery of electric stimulations of the sciatic nerve (100 Hz with 1-ms pulse and 3-s duration). Following 50 repeated maximal isometric contractions, the protein expressions of BDNF and activation of its receptor in the hippocampus significantly increased compared with the sham-operated control rats. However, the expression of both BDNF and FNDC5 within stimulated muscles did not significantly increase, nor did their serum concentrations change. These results indicate that local muscular contractions under unconsciousness can induce BDNF expression in the hippocampus. This effect may be mediated by peripheral reception of muscle contraction, but not by systemic factors.

Ectopic expression of Miro 1 ameliorates seizures and inhibits hippocampal neurodegeneration in a mouse model of pilocarpine epilepsy.

Epilepsy is a common disease of the central nervous system. This study aimed to investigate the role of mitochondrial Rho (Miro) 1 in epilepsy, using a mouse model of pilocarpine-induced status epilepticus (SE). Intraperitoneal injection of pilocarpine induced epileptic seizures in mice and significantly decreased Miro 1 expression in the hippocampus. Moreover, pilocarpine treatment increased the serum levels of heat shock protein 70 (HSP70) and S100 calcium binding protein B (S100B) and led to hippocampal neuronal injury and apoptosis. The intrinsic apoptotic pathway was activated in the hippocampal neurons following pilocarpine-induced SE, as evidenced by increased levels of cleaved caspase-3 and Bax, downregulation of Bcl-2, and the release of cytochrome c from mitochondria to cytoplasm. By contrast, forced expression of Miro 1 by lateral ventricular administration of adenovirus mitigated pilocarpine-induced epileptic seizures, reduced the elevation of HSP70 and S100B, and inhibited hippocampal neuronal apoptosis by suppressing the intrinsic apoptotic pathway. In summary, our data demonstrates that ectopic expression of Miro 1 alleviated pilocarpine-induced SE and protected hippocampal neurons by inhibiting the intrinsic apoptotic pathway. These findings provide new insights into epileptic disorders and suggest a potential neuroprotective value of Miro 1 in the treatment of epilepsy.

NMDA receptors in the dorsal hippocampal area are involved in tramadol state-dependent memory of passive avoidance learning in mice.

The precise neurobiological mechanisms of tramadol abuse underlying the cognitive function are still unknown. The aim of the present study was to examine the possible effects of intra-CA1 injections of N-methyl-d-aspartate (NMDA), a glutamate NMDA receptor (NMDAR) agonist, and d,l-2-amino-5-phosphonopentanoic acid (DL-AP5), a competitive NMDAR antagonist, on tramadol state-dependent memory. A single-trial step-down passive avoidance task was used for the assessment of memory retrieval in adult male NMRI mice. Post-training i.p. administration of an atypical µ-opioid receptor agonist, tramadol (2.5 and 5 mg/kg), dose-dependently induced impairment of memory retention. Pre-test injection of tramadol (2.5 and 5 mg/kg) induced state-dependent retrieval of the memory acquired under post-training administration of tramadol (5 mg/kg) influence. Pre-test intra-CA1 injection of NMDA (10-5 and 10-4 µg/mouse) 5 min before the administration of tramadol (5 mg/kg, i.p.) dose-dependently inhibited tramadol state-dependent memory. Pre-test intra-CA1 injection of DL-AP5 (0.25 and 0.5 µg/mouse) reversed the memory impairment induced by post-training administration of tramadol (5 mg/kg). Pre-test administration of DL-AP5 (0.25 and 0.5 µg/mouse) with an ineffective dose of tramadol (1.25 mg/kg) restored the retrieval and induced tramadol state-dependent memory. It can be concluded that dorsal hippocampal NMDAR mechanisms play an important role in the modulation of tramadol state-dependent memory.

Preconditioning with morphine protects hippocampal CA1 neurons from ischemia-reperfusion injury via activation of the mTOR pathway.

The signaling pathway of chronic morphine treatment to prevent neuronal damage following transient cerebral ischemia is not clear. In this study, we examined the role of mammalian target of rapamycin (mTOR) to identify the neuroprotective effects of chronic morphine preconditioning on the hippocampus following ischemia-reperfusion (I/R) injury. Morphine was administered for 5 days, twice a day, before inducing I/R injury. The possible role of mTOR was evaluated by the injection of rapamycin (5 mg/kg body weight, by intraperitoneal injection) before I/R was induced. The passive avoidance test was used to evaluate memory performance. Neuronal density and apoptosis were measured in the CA1 region, 72 h after I/R injury. The expressions of mTOR and phosphorylated mTOR (p-mTOR), as well as superoxide dismutase (SOD) activity were determined 24 h after I/R injury. Chronic morphine treatment attenuated apoptosis and neuronal loss in the hippocampus after I/R injury, which led to improvement in memory (P < 0.05 vs. untreated I/R) and increase in the expression of p-mTOR (P < 0.05 vs. untreated I/R) and SOD activity (P < 0.05 vs. untreated I/R) in the hippocampus. Pretreatment with rapamycin abolished all the above-mentioned protective effects. These results describe novel findings whereby chronic morphine preconditioning in hippocampal CA1 neurons is mediated by the mTOR pathway, and through increased phosphorylation of mTOR can alleviate oxidative stress and apoptosis, and eventually protect the hippocampus from I/R injury.

[Hippocampus, brainstem and brain dose-volume constraints for fractionated 3-D radiotherapy and for stereotactic radiation therapy: Limits and perspectives]. / Contraintes de dose en radiothérapie conformationnelle fractionnée et en radiothérapie stéréotaxique dans les hippocampes, le tronc cérébral et l'encéphale : limites et perspectives.

Cerebral radiation-induced toxicities after radiotherapy (RT) of brain tumors are frequent. The protection of organs at risk (OAR) is crucial, especially for brain tumors, to preserve cognition in cancer survivors. Dose constraints of cerebral OAR used in conventional RT, radiosurgery (SRS) and stereotactic radiotherapy (SRT) are debated. In fact, they are based on historical cohorts or calculated with old mathematical models. Values of α/ß ratio of cerebral OAR are also controversial leading to misestimate the equivalent dose in 2Gy fractions or the biological equivalent dose, especially during hypofractionated RT. Although recent progresses in medical imaging, the diagnosis of radionecrosis remains difficult. In this article, we propose a large review of dose constraints used for three major cerebral OAR: the brain stem, the hippocampus and the brain.

Effect of tolbutamide on tetraethylammonium-induced postsynaptic zinc signals at hippocampal mossy fiber-CA3 synapses.

The application of tetraethylammonium (TEA), a blocker of voltage-dependent potassium channels, can induce long-term potentiation (LTP) in the synaptic systems CA3-CA1 and mossy fiber-CA3 pyramidal cells of the hippocampus. In the mossy fibers, the depolarization evoked by extracellular TEA induces a large amount of glutamate and also of zinc release. It is considered that zinc has a neuromodulatory role at the mossy fiber synapses, which can, at least in part, be due to the activation of presynaptic ATP-dependent potassium (KATP) channels. The aim of this work was to study properties of TEA-induced zinc signals, detected at the mossy fiber region, using the permeant form of the zinc indicator Newport Green. The application of TEA caused a depression of those signals that was partially blocked by the KATP channel inhibitor tolbutamide. After the removal of TEA, the signals usually increased to a level above baseline. These results are in agreement with the idea that intense zinc release during strong synaptic events triggers a negative feedback action. The zinc depression, caused by the LTP-evoking chemical stimulation, turns into potentiation after TEA washout, suggesting the existence of a correspondence between the observed zinc potentiation and TEA-evoked mossy fiber LTP.

Osthole prevents cerebral ischemia-reperfusion injury via the Notch signaling pathway.

Stroke is a common cerebrovascular disease in aging populations, and constitutes the second highest principle cause of mortality and the principle cause of permanent disability, and ischemic stroke is the primary form. Osthole is a coumarin derivative extracted from the fruits of Cnidium monnieri (L.) Cusson. In this study, we established a rat model of middle cerebral artery occlusion/reperfusion (MCAO/R) in vivo and found that MCAO/R caused cerebral infarction, hippocampus neuronal injury and apoptosis, and also activated the Notch 1 signaling pathway. However, treatment with osthole further enhanced the activity of Notch 1 signaling and reduced the cerebral infarction as well as the hippocampus neuronal injury and apoptosis induced by MCAO/R in a dose-dependent manner. The same results were observed in a primary neuronal oxygen glucose deficiency/reperfusion (OGD/R) model in vitro, and the effect of osthole could be blocked by an inhibitor of Notch 1 signaling, N-[N-(3,5-difluorophenacetyl)-l-alanyl]-S-phenylglycine tert-butyl ester (DAPT). Therefore, we demonstrated that osthole injection prevented rat ischemia-reperfusion injury via activating the Notch 1 signaling pathway in vivo and in vitro in a dose-dependent manner, which may be significant for clinical treatment of ischemic stroke.

Curcumin protects neuronal cells against status-epilepticus-induced hippocampal damage through induction of autophagy and inhibition of necroptosis.

Status epilepticus, the most severe form of epilepsy, is characterized by progressive functional and structural damage in the hippocampus, ultimately leading to the development and clinical appearance of spontaneous, recurrent seizures. Although the pathogenesis underlying epileptogenesis processes remains unclear, a substantial body of evidence has shown that status epilepticus acts as an important initial factor in triggering epileptogenesis. Notably, besides classical cell death mechanisms such as apoptosis and necrosis, 2 novel regulators of cell fate known as necroptosis and autophagy, are demonstrated to be involved in neuronal damage in various neurodegenerative and neuropsychiatric disorders. However, whether necroptosis and autophagy play a role in post-status-epilepticus rat hippocampus and other epilepsy mechanisms deserves further research effort. In addition, research is needed to determine whether compounds from traditional Chinese herbs possess antiepileptic effects through the modulation of necroptosis and autophagy. In this study, we found that curcumin, a polyphenolic phytochemical extracted from the Curcuma longa plant, protects neuronal cells against status-epilepticus-induced hippocampal neuronal damage in the lithium-pilocarpine-induced status epilepticus rat model through induction of autophagy and inhibition of necroptosis.

Fish oil and treadmill exercise have age-dependent effects on episodic memory and oxidative state of the hippocampus.

There is a growing interest to better understand how lifestyle choices can improve memory functions. Treadmill exercise and long-chain n-3 polyunsaturated fatty acids found in fish oil are able to stimulate hippocampal antioxidant defenses and improve memory. The aim was to test whether fish oil and exercise can improve rat's performance on memory tasks and optimize hippocampal antioxidant state in an age-dependent manner. Therefore, young and adult rats were exercised and received fish oil during 4 weeks. The exercise was performed for 30 min/day, with the speed gradually increasing from the first to the last week. Afterwards, episodic memory was measured by the recognition of object identity and spatial location. Hippocampal oxidative state was investigated with the levels of malondialdehyde (MDA), carbonyls content, antioxidant enzymatic activity (superoxide dismutase (SOD), catalase (CAT)), and antioxidant nonenzymatic activity (reduced glutathione, sulfhydryl content). The adult rats treated with fish oil and exercise (FO&EX) were able to recognize object's shape and placement; however, FO&EX young rats had impaired spatial recognition (p < 0.05). The FO&EX young rats did not have reduced MDA or carbonyl content, though either fish oil or exercise reduced MDA (p < 0.05) and carbonyl levels (p < 0.01). Exercise increased SOD (p < 0.001) and CAT activities (p < 0.05), and fish oil enhanced SOD activity (p < 0.05) in young rats. At adulthood, exercise increased MDA levels (p < 0.05), and FO&EX reduced MDA (p < 0.001). Finally, exercise and fish oil improved nonenzymatic antioxidant defense (p < 0.05) only in adult rats. Results support age-dependent effects of fish oil and exercise on memory and oxidative state of the hippocampus during either neurodevelopment or adulthood.