What are the best animal models for testing early intervention in cerebral palsy?

Interventions to treat cerebral palsy should be initiated as soon as possible in order to restore the nervous system to the correct developmental trajectory. One drawback to this approach is that interventions have to undergo exceptionally rigorous assessment for both safety and efficacy prior to use in infants. Part of this process should involve research using animals but how good are our animal models? Part of the problem is that cerebral palsy is an umbrella term that covers a number of conditions. There are also many causal pathways to cerebral palsy, such as periventricular white matter injury in premature babies, perinatal infarcts of the middle cerebral artery, or generalized anoxia at the time of birth, indeed multiple causes, including intra-uterine infection or a genetic predisposition to infarction, may need to interact to produce a clinically significant injury. In this review, we consider which animal models best reproduce certain aspects of the condition, and the extent to which the multifactorial nature of cerebral palsy has been modeled. The degree to which the corticospinal system of various animal models human corticospinal system function and development is also explored. Where attempts have already been made to test early intervention in animal models, the outcomes are evaluated in light of the suitability of the model

Specialist palliative care nursing and the philosophy of palliative care: a critical discussion

Nursing is the largest regulated health professional workforce providing palliative care across a range of clinical settings. Historically, palliative care nursing has been informed by a strong philosophy of care which is soundly articulated in palliative care policy, research and practice. Indeed, palliative care is now considered to be an integral component of nursing practice regardless of the specialty or clinical setting. However, there has been a change in the way palliative care is provided. Upstreaming and mainstreaming of palliative care and the dominance of a biomedical model with increasing medicalisation and specialisation are key factors in the evolution of contemporary palliative care and are likely to impact on nursing practice. Using a critical reflection of the authors own experiences and supported by literature and theory from seminal texts and contemporary academic, policy and clinical literature, this discussion paper will explore the influence of philosophy on nursing knowledge and theory in the context of an evolving model of palliative care

オンガクゲキ ヒョウゲン カテイ ニオケル ガイテキ ナイテキ ケイショウ ノ イミ : オンガクゲキ キャクホン ツタカズラ コマチデン オ ジレイ トシテ

The purpose of this paper is to consider the meaning of external, internal images in the process of expression on music drama. The major results of this consideration can be summarized as follows: The external image is the "form" of reality, embodiment, that is to say, something visible and audible. On the other hand, the internal image is the simbolic form of idea, imagination, visions, enviromental factor, affect (i. e. substance of consciousness, etc.), that is to say, samething invisible. And the expression in the Music Drama is itself the mental act of representing subject subsisted in emotion and reality from expression, such as singing, acting and the theatrical line, etc..国立情報学研究所『研究紀要公開支援事業』により電子化

Increased hippocampal excitability in miR-324-null mice

MicroRNAs are non-coding RNAs that act to downregulate the expression of target genes by translational repression and degradation of messenger RNA molecules. Individual microRNAs have the ability to specifically target a wide array of gene transcripts, therefore allowing each microRNA to play key roles in multiple biological pathways. miR-324 is a microRNA predicted to target thousands of RNA transcripts and is expressed far more highly in the brain than in any other tissue, suggesting that it may play a role in one or multiple neurological pathways. Here we present data from the first global miR-324-null mice, in which increased excitability and interictal discharges were identified in vitro in the hippocampus. RNA sequencing was used to identify differentially expressed genes in miR-324-null mice which may contribute to this increased hippocampal excitability, and 3′UTR luciferase assays and western blotting revealed that two of these, Suox and Cd300lf, are novel direct targets of miR-324. Characterisation of microRNAs that produce an effect on neurological activity, such as miR-324, and identification of the pathways they regulate will allow a better understanding of the processes involved in normal neurological function and in turn may present novel pharmaceutical targets in treating neurological disease

The Corticofugal Neuron-Associated Genes ROBO1, SRGAP1, and CTIP2 Exhibit an Anterior to Posterior Gradient of Expression in Early Fetal Human Neocortex Development

Developing neocortical progenitors express transcription factors in gradients that induce programs of region-specific gene expression. Our previous work identified anteriorly upregulated expression gradients of a number of corticofugal neuron-associated gene probe sets along the anterior–posterior axis of the human neocortex (8-12 postconceptional weeks [PCW]). Here, we demonstrate by real-time polymerase chain reaction, in situ hybridization and immunohistochemistry that 3 such genes, ROBO1, SRGAP1, and CTIP2 are highly expressed anteriorly between 8-12 PCW, in comparison with other genes (FEZF2, SOX5) expressed by Layer V, VI, and subplate neurons. All 3 were prominently expressed by early postmitotic neurons in the subventricular zone, intermediate zone, and cortical plate (CP) from 8 to 10 PCW. Between 12 and 15 PCW expression patterns for ER81 and SATB2 (Layer V), TBR1 (Layer V/VI) and NURR1 (Layer VI) revealed Layer V forming. By 15 PCW, ROBO1 and SRGAP1 expression was confined to Layer V, whereas CTIP2 was expressed throughout the CP anteriorly. We observed ROBO1 and SRGAP1 immunoreactivity in medullary corticospinal axons from 11 PCW onward. Thus, we propose that the coexpression of these 3 markers in the anterior neocortex may mark the early location of the human motor cortex, including its corticospinal projection neurons, allowing further study of their early differentiation

Improving outcomes in cerebral palsy with early intervention: new translational approaches

The aim of this Research Topic was to collate articles describing prediction of outcomes of pre- and perinatal lesions leading to cerebral palsy, basic research in animal models and human subjects, and ideas for, and trials of, interventions in the first two years of life.CP arises from insults to the sensorimotor cortex, subcortical axon tracts and subplate. The aetiology is complex and often multifactorial. The outcome is not simply a loss of voluntary control due to disruption of descending pathways, but also involves abnormal development of reflex and corticospinal circuitry. CP may be viewed as aberrant plasticity in response to a lesion, indeed, abnormalities in movement are subtle at first but develop subsequently. It is misleading to suppose that developmental mechanisms are self-reparative. The challenge is to understand activitydependent fine tuning of neural circuitry during normal development and to find how to promote desirable plasticity whilst limiting undesirable effects following developmental lesions. However, before proposing interventions, we have to develop our ability to predict the severity of neonatal insults.We solicited a variety of articles, including long and short reviews, original research and opinion pieces, from both basic scientists and clinicians. Likewise we, as editors, have complementary knowledge and experience in this area. Anna Basu is an academic pediatric neurologist and Gavin Clowry is a developmental neuroscientist

Mechanical Flexibility Reduces the Foreign Body Response to Long-Term Implanted Microelectrodes in Rabbit Cortex.

Micromotion between the brain and implanted electrodes is a major contributor to the failure of invasive microelectrodes. Movements of the electrode tip cause recording instabilities while spike amplitudes decline over the weeks/months post-implantation due to glial cell activation caused by sustained mechanical trauma. We compared the glial response over a 26-96 week period following implantation in the rabbit cortex of microwires and a novel flexible electrode. Horizontal sections were used to obtain a depth profile of the radial distribution of microglia, astrocytes and neurofilament. We found that the flexible electrode was associated with decreased gliosis compared to the microwires over these long indwelling periods. This was in part due to a decrease in overall microgliosis and enhanced neuronal density around the flexible probe, especially at longer periods of implantation