A Digital Atlas of the Dog Brain

There is a long history and a growing interest in the canine as a subject of study in neuroscience research and in translational neurology. In the last few years, anatomical and functional magnetic resonance imaging (MRI) studies of awake and anesthetized dogs have been reported. Such efforts can be enhanced by a population atlas of canine brain anatomy to implement group analyses. Here we present a canine brain atlas derived as the diffeomorphic average of a population of fifteen mesaticephalic dogs. The atlas includes: 1) A brain template derived from in-vivo, T1-weighted imaging at 1 mm isotropic resolution at 3 Tesla (with and without the soft tissues of the head); 2) A co-registered, high-resolution (0.33 mm isotropic) template created from imaging of ex-vivo brains at 7 Tesla; 3) A surface representation of the gray matter/white matter boundary of the high-resolution atlas (including labeling of gyral and sulcal features). The properties of the atlas are considered in relation to historical nomenclature and the evolutionary taxonomy of the Canini tribe. The atlas is available for download (https://cfn.upenn.edu/aguirre/wiki/public:data_plosone_2012_datta)

Ponte et stratégie de la reproduction chez les femelles du tacaud Trisopterus luscus (Gadidés) du plateau continental de la Galice, nord-ouest de l'Espagne

[EN] Pouting, Trisopterus luscus is harvested commercially on the Galician shelf by the Spanish inshore artisanal fleet. In spite of a substantial decrease in pouting catches, fishery regulations are limited to size length restrictions. This study provides biological data including length-at-maturity based on histological methods, seasonal maturation, spawning and fecundity. A collection 443 females, from 17 to 42 cm in total length, were sampled from landings (December 2003 to December 2004). Pouting length-at-maturity was estimated as 19.2 cm on average. Pouting females in spawning condition were observed throughout the year and the number of developing oocytes ranged from 20 000 to 1 327 000. Peak spawning was observed between February and April, which correlated well with trends in gonadosomatic index, and inverse to condition factor and hepatosomatic index. Histological examination of the gonads revealed that pouting ovarian development organization is asynchronous, and fecundity is probably determinate.[FR] Le tacaud, Trisopterus luscus est pêché par la flotte artisanale espagnole. En dépit d'une diminution substantielle des captures de tacaud, la pêche est réglementée uniquement à partir d'une taille minimum commerciale. Cette étude fournit des données biologiques comprenant la taille à maturité sexuelle basée sur l'histologie, la maturation saisonnière, la ponte et la fécondité. Un échantillon de 443 femelles, de 17 à 42 cm longueur totale, est examiné à partir des débarquements durant une année (de décembre 2003 à décembre 2004). La taille moyenne à maturité sexuelle est estimée à 19,2 cm. Les femelles de tacaud en condition de ponte sont observée tout au long de l'année et le nombre d'ovocytes s'étend de 20 000 to 1 327 000 par individu. Les pics de ponte sont observés entre février et avril, ce qui est bien corrélé avec l'évolution du rapport gonado-somatique et inverse de celle du facteur de condition et du rapport hépato-somatique. L'étude histologique révèle que le développement ovarien chez le tacaud est asynchrone, et que la fécondité est probablement déterminée.Peer reviewe

CNS Penetration of Intrathecal-Lumbar Idursulfase in the Monkey, Dog and Mouse: Implications for Neurological Outcomes of Lysosomal Storage Disorder

A major challenge for the treatment of many central nervous system (CNS) disorders is the lack of convenient and effective methods for delivering biological agents to the brain. Mucopolysaccharidosis II (Hunter syndrome) is a rare inherited lysosomal storage disorder resulting from a deficiency of iduronate-2-sulfatase (I2S). I2S is a large, highly glycosylated enzyme. Intravenous administration is not likely to be an effective therapy for disease-related neurological outcomes that require enzyme access to the brain cells, in particular neurons and oligodendrocytes. We demonstrate that intracerebroventricular and lumbar intrathecal administration of recombinant I2S in dogs and nonhuman primates resulted in widespread enzyme distribution in the brain parenchyma, including remarkable deposition in the lysosomes of both neurons and oligodendrocytes. Lumbar intrathecal administration also resulted in enzyme delivery to the spinal cord, whereas little enzyme was detected there after intraventricular administration. Mucopolysaccharidosis II model is available in mice. Lumbar administration of recombinant I2S to enzyme deficient animals reduced the storage of glycosaminoglycans in both superficial and deep brain tissues, with concurrent morphological improvements. The observed patterns of enzyme transport from cerebrospinal fluid to the CNS tissues and the resultant biological activity (a) warrant further investigation of intrathecal delivery of I2S via lumbar catheter as an experimental treatment for the neurological symptoms of Hunter syndrome and (b) may have broader implications for CNS treatment with biopharmaceuticals

Translational models for vascular cognitive impairment: a review including larger species.

BACKGROUND: Disease models are useful for prospective studies of pathology, identification of molecular and cellular mechanisms, pre-clinical testing of interventions, and validation of clinical biomarkers. Here, we review animal models relevant to vascular cognitive impairment (VCI). A synopsis of each model was initially presented by expert practitioners. Synopses were refined by the authors, and subsequently by the scientific committee of a recent conference (International Conference on Vascular Dementia 2015). Only peer-reviewed sources were cited. METHODS: We included models that mimic VCI-related brain lesions (white matter hypoperfusion injury, focal ischaemia, cerebral amyloid angiopathy) or reproduce VCI risk factors (old age, hypertension, hyperhomocysteinemia, high-salt/high-fat diet) or reproduce genetic causes of VCI (CADASIL-causing Notch3 mutations). CONCLUSIONS: We concluded that (1) translational models may reflect a VCI-relevant pathological process, while not fully replicating a human disease spectrum; (2) rodent models of VCI are limited by paucity of white matter; and (3) further translational models, and improved cognitive testing instruments, are required

Progress in gene therapy for neurological disorders

Diseases of the nervous system have devastating effects and are widely distributed among the population, being especially prevalent in the elderly. These diseases are often caused by inherited genetic mutations that result in abnormal nervous system development, neurodegeneration, or impaired neuronal function. Other causes of neurological diseases include genetic and epigenetic changes induced by environmental insults, injury, disease-related events or inflammatory processes. Standard medical and surgical practice has not proved effective in curing or treating these diseases, and appropriate pharmaceuticals do not exist or are insufficient to slow disease progression. Gene therapy is emerging as a powerful approach with potential to treat and even cure some of the most common diseases of the nervous system. Gene therapy for neurological diseases has been made possible through progress in understanding the underlying disease mechanisms, particularly those involving sensory neurons, and also by improvement of gene vector design, therapeutic gene selection, and methods of delivery. Progress in the field has renewed our optimism for gene therapy as a treatment modality that can be used by neurologists, ophthalmologists and neurosurgeons. In this Review, we describe the promising gene therapy strategies that have the potential to treat patients with neurological diseases and discuss prospects for future development of gene therapy