Neurogenesis in a young dog with epileptic seizures

Epileptic seizures can lead to various reactions in the brain, ranging from neuronal necrosis and glial cell activation to focal structural disorganization. Furthermore, increased hippocampal neurogenesis has been documented in rodent models of acute convulsions. This is a report of hippocampal neurogenesis in a dog with spontaneous epileptic seizures. A 16-week-old epileptic German Shepherd Dog had marked neuronal cell proliferation (up to 5 mitotic figures per high-power field and increased immunohistochemical expression of proliferative cell nuclear antigen) in the dentate gyrus accompanied by microglial and astroglial activation. Some granule cells expressed doublecortin, a marker of immature neurons; mitotically active cells expressed neuronal nuclear antigen. No mitotic figures were found in the brain of age-matched control dogs. Whether increased neurogenesis represents a general reaction pattern of young epileptic dogs should be investigated.     

Postnatal neurogenesis: of mice, men, and macaques

Over the past 20 years, the conception of brain development has radically changed from a fixed and limited hierarchical process to a more plastic and continuous one. Most surprising, the field has learned that postnatal neurogenesis is not just a seasonal phenomenon in songbirds but a process that occurs across species and seasons. Astrocytes, whose primary role in the central nervous system was thought to be strictly supportive, have emerged as a heterogeneous population, a subset of which is the neural stem cell. Postnatal neurogenesis persists in specialized niches within the rostral subventricular zone and hippocampal dentate gyrus and, for a limited period, within the white matter tracts and external granular layer of the cerebellum. These specialized microenvironments are influenced by factors in the blood, cerebrospinal fluid, and local extracellular matrix. This article reviews the current understanding of adult neurogenesis, which is conserved across many vertebrate species, underscoring the value of animal models in past and present studies of human neurogenesis and neurogenic disease.     

Neurogenesis in Neurotoxin-induced Animal Models for Parkinson's Disease-A Review of the Current Status

Animal models for Parkinson's disease (PD) are essential for understanding its pathogenesis and for development and testing of new therapies. Discoveries of endogenous neurogenesis in the adult mammalian brain give new insight into the cell-based approach for treatment of neurodegenerative disorders, such as PD. Although a great deal of interest has been focused on endogenous neurogenesis in neurotoxin-induced animal models for PD, it still remains controversial whether neural stem cells migrate into the injured area and contribute to repopulation of depleted dopaminergic neurons in neurotoxin-injured adult brains. The purpose of this review is to examine the data available regarding neurogenesis in neurotoxin-induced animal models of PD. It is hoped that data from the animal investigations available in the literature will promote understanding of the neurotoxin-induced animal models for PD.     

Adult neurogenesis in the mammalian dentate gyrus

Earlier observations in neuroscience suggested that no new neurons form in the mature central nervous system. Evidence now indicates that new neurons do form in the adult mammalian brain. Two regions of the mature mammalian brain generate new neurons: (a) the border of the lateral ventricles of the brain (subventricular zone) and (b) the subgranular zone (SGZ) of the dentate gyrus of the hippocampus. This review focuses only on new neuron formation in the dentate gyrus of the hippocampus. During normal prenatal and early postnatal development, neural stem cells (NSCs) give rise to differentiated neurons. NSCs persist in the dentate gyrus SGZ, undergoing cell division, with some daughter cells differentiating into functional neurons that participate in learning and memory and general cognition through integration into pre-existing neural networks. Axons, which emanate from neurons in the entorhinal cortex, synapse with dendrites of the granule cells (small neurons) of the dentate gyrus. Axons from granule cells synapse with pyramidal cells in the hippocampal CA3 region, which send axons to synapse with CA1 hippocampal pyramidal cells that send their axons out of the hippocampus proper. Adult neurogenesis includes proliferation, differentiation, migration, the death of some newly formed cells and final integration of surviving cells into neural networks. We summarise these processes in adult mammalian hippocampal neurogenesis and discuss the roles of major signalling molecules that influence neurogenesis, including neurotransmitters and some hormones. The recent controversy raised concerning whether or not adult neurogenesis occurs in humans also is discussed.     

Age-dependent changes in progranulin expression in the mouse brain

The progranulin (PGRN) gene is involved in sexual differentiation of the brain during the perinatal period and estrogen-induced adult neurogenesis in the hippocampus. Mutations in the PGRN gene are also implicated in human frontotemporal lobar degeneration. Thus, while PGRN appears to play important roles as a growth factor in the brain, the localization of PGRN-expressing cells throughout the brain has not been fully established. In the present study, we examined the localization of PGRN proteins in the brain using adult male wild-type mice and PGRN-deficient mice we had generated previously. We also evaluated age-dependent changes in PGRN expression at the mRNA and protein levels. As expected, no immunoreactivity was observed in the brains of the PGRN-deficient mice. In the wild-type mice, intense immunoreactivity was observed in several brain regions including the cingulate and piriform cortices, the pyramidal cell layer and dentate gyrus of the hippocampus, the amygdala, the ventromedial and arcuate nuclei of the hypothalamus and the Purkinje cell layer in the cerebellum. Moreover, PGRN mRNA and protein expression decreased in the cortex, hippocampus and hypothalamus in an age-dependent manner. Since many of these brain regions are involved in emotion, memory and recognition, PGRN may play roles as a growth factor in these brain functions that decline with age.     

REGIONAL BINDING INDEX OF THE RADIOLABELED SELECTIVE 5-HT2A ANTAGONIST 123I-5-I-R91150 IN THE NORMAL CANINE BRAIN IMAGED WITH SINGLE PHOTON EMISSION COMPUTED TOMOGRAPHY

The pattern of the specific 5-HT2A (5-hydroxytryptamine 2A receptor) antagonist 123I-5-I-R91150 was measured in 10 healthy dogs without neurologic and behavior abnormalities. Eight cortical regions (left and right fronto-, temporo-, parieto-, and occipitocortical area), one global subcortical region (including the thalamic system) were compared with a reference region lacking receptors; that is, the cerebellum. The 123I labeled radioligand was injected intravenously 100-200 minutes before acquisition. Both transmission and emission data were obtained with a triple head gamma camera equipped with high-resolution fanbeam collimators. The emission data were corrected for scatter and attenuation. To delineate different cerebral regions more accurately, the regions of interest (ROI) defined in a former study on brain perfusion measured with 99mTc-ethyl cysteinate dimer (ECD) in the same dogs were used. The co-registration of the 99mTc-ECD and the 123I-5-I-R91150, obtained from each dog, was realized with the help of corresponding transmission maps. By normalizing each regional cerebral activity to the activity observed in the cerebellum, the regional radioactivity (binding index) could be relatively quantified. Highest brain uptake was noted in the frontocortical brain areas (right: 1.85, left: 1.89), followed by the temporocortical region (right: 1.58, left: 1.56). Least uptake was noted in the more caudal and middle brain regions [occipito- (right: 1.46, left: 1.41), parietocortical (right: 1.30, left: 1.26), and striatal region (1.19)]. No gender nor age influence was noted in this series. The 123I labeled serotonin-2A receptor ligand seems to have similar cortical binding in the normal canine brain, as shown in humans and other animal species. A frontocortical to occipitocortical (rostrocaudal) binding index gradient was identified within the dog, which has not been seen in imaging studies from humans and other animal species. The significance of these results will need further investigation. This normative data can be used to compare regional brain uptake of the 123I-radioligand to dogs with behavioral disorders related to the serotonergic system, in future studies.     

CCL2 induces neural stem cell proliferation and neuronal differentiation in Niemann-Pick type C mice

Niemann-Pick type C disease (NP-C) is a rare and ultimately fatal lysosomal storage disorder with variable neurologic symptoms. Loss of neuronal function and neuronal cell death occur in the NP-C brain, similar to the findings for other neurodegenerative diseases. Targeting of neuronal cells in the brain therefore represents a potential clinical intervention strategy to reduce the rate of disease progression and improve the quality of life. We previously reported that bone marrow stem cells show a neurogenic effect through CCL2 (also known as monocyte chemoattractant protein-1, MCP-1) secretion in the brains of NP-C mice. However, the direct effect of CCL2 on neurogenesis has not been ascertained. Here, to define neurogenic effects of CCL2 in NP-C, we applied human recombinant CCL2 to neural stem cells (NSCs) derived from NP-C mice. CCL2-treated NSCs showed significantly increased capacity for self-renewal, proliferation and neuronal differentiation. Similar results were observed in the subventricular zone of NP-C mice after CCL2 treatment. Furthermore, infusion of CCL2 into the NP-C mouse brain resulted in reduction of neuroinflammation. Taken together, our results demonstrate that CCL2 is a potential new therapeutic agent for NP-C.     

Incidence, immunity and treatment of feline dermatophytosis

Feline dermatophytosis is a superficial skin infection characterized by the invasion of cornified tissues such as hair and nails.This infection is nearly always caused by Microsporum canis. Infected animals release infective spores in the environment which will then contaminate other animals or humans. Infected animals usually develop immunity so the infection will spontaneously disappear after a few weeks to months. Long haired and immunocom-promised cats do not have the same ability to acquire resistance and spontaneous recovery does usually not occur. The treatment of such an infection will require topical and systemic treatment of all contaminated and in-contact cats. The use of desinfectants such as bleach or enilconazole has been proven effective to destroy the spores in the environment. In addition, the efficacy of topical and systemic treatments with azole derivates or allylamines has also been demonstrated in several studies. On the contrary, dermatophyte vaccination has never been proven effective in well controlled studies. Regular follow-up and fungal cultures are mandatory to ensure succesfull treatment.     

Foot-and-mouth disease: past,present and future

Foot-and-mouth disease (FMD) is a highly contagious disease of cloven-hoofed animals including cattle, pigs, sheep and many wildlife species. It can cause enormous economic losses when incursions occur into countries which are normally disease free. In addition, it has long-term effects within countries where the disease is endemic due to reduced animal productivity and the restrictions on international trade in animal products. The disease is caused by infection with foot-and-mouth disease virus (FMDV), a picornavirus. Seven different serotypes (and numerous variants) of FMDV have been identified. Some serotypes have a restricted geographical distribution, e.g. Asia-1, whereas others, notably serotype O, occur in many different regions. There is no cross-protection between serotypes and sometimes protection conferred by vaccines even of the same serotype can be limited. Thus it is important to characterize the viruses that are circulating if vaccination is being used for disease control. This review describes current methods for the detection and characterization of FMDVs. Sequence information is increasingly being used for identifying the source of outbreaks. In addition such information can be used to understand antigenic change within virus strains. The challenges and opportunities for improving the control of the disease within endemic settings, with a focus on Eurasia, are discussed, including the role of the FAO/EuFMD/OIE Progressive Control Pathway. Better control of the disease in endemic areas reduces the risk of incursions into disease-free regions.     

Fast neutron irradiation deteriorates hippocampus-related memory ability in adult mice

Object recognition memory and contextual fear conditioning task performance in adult C57BL/6 mice exposed to cranial fast neutron irradiation (0.8 Gy) were examined to evaluate hippocampus-related behavioral dysfunction following acute exposure to relatively low doses of fast neutrons. In addition, hippocampal neurogenesis changes in adult murine brain after cranial irradiation were analyzed using the neurogenesis immunohistochemical markers Ki-67 and doublecortin (DCX). In the object recognition memory test and contextual fear conditioning, mice trained 1 and 7 days after irradiation displayed significant memory deficits compared to the sham-irradiated controls. The number of Ki-67- and DCX-positive cells decreased significantly 24 h post-irradiation. These results indicate that acute exposure of the adult mouse brain to a relatively low dose of fast neutrons interrupts hippocampal functions, including learning and memory, possibly by inhibiting neurogenesis.     

EFNA5基因生理功能的研究进展

肝配蛋白A5(Ephrin A5,EFNA5)是受体酪氨酸激酶家族(RTKs)成员之一,定位于细胞膜,在皮肤、脑、脾、肾脏、心脏和脂肪中均有较高表达。EFNA5能够与其受体结合发挥重要的生理功能,如参与神经发生、血管生成、促进细胞增殖与分化、平衡葡萄糖稳态、维持晶状体发育、调控雌性哺乳动物生殖、动员脂肪产热等。本文对EFNA5基因的定位、结构特征、生理功能、在癌症及畜牧等方面的研究现状进行综述,以期为EFNA5的进一步探究提供参考。     

DIFFUSION‐WEIGHTED MAGNETIC RESONANCE IMAGING OF THE NORMAL CANINE BRAIN

Diffusion‐weighted imaging (DWI) MRI has been primarily reported as a method for diagnosing cerebrovascular disease in veterinary patients. In humans, clinical applications for diffusion‐weighted MRI have also included epilepsy, Alzheimer's, and Creutzfeld–Jakob disease. Before these applications can be developed in veterinary patients, more data on brain diffusion characteristics are needed. Therefore, the aim of this study was to evaluate the distribution of diffusion in the normal canine brain. Magnetic resonance imaging of the brain was performed in ten, clinically normal, purpose‐bred beagle dogs. On apparent diffusion coefficient maps, regions of interest were drawn around the caudate nucleus, thalamus, piriform lobe, hippocampus, semioval center, and cerebral cortex. Statistically significant differences in mean apparent diffusion coefficient were found for the internal capsule, hippocampus, and thalamus. The highest apparent diffusion coefficient (1044.29 ± 165.21 μm²/s (mean ± SD (standard deviation)) was detected in the hippocampus. The lowest apparent diffusion coefficient was measured in the semioval center (721.39 ± 126.28 μm²/s (mean ± SD)). Significant differences in mean apparent diffusion coefficients of the caudate nucleus, thalamus, and piriform lobe were found by comparing right and left sides. Differences between brain regions may occur due to differences in myelination, neural density, or fiber orientation. The reason for the differences between right and left sides remains unclear. Data from the current study provide background for further studies of diffusion changes in dogs with brain disease.     

Sodium distribution in the bovine brain

Fatal sodium intoxication can occur in many species, including cattle, and postmortem confirmation often includes brain sodium concentration determination. Published information regarding brain sodium distribution in cattle was not found in a literature review. Our study was designed to determine whether sodium is uniformly distributed throughout the bovine brain. Eight whole bovine brains were collected from adult cattle with no neurologic signs or history suggestive of sodium intoxication, and with a non-neurologic cause of death diagnosed on gross examination. Brains were divided mid-sagittally. One hemisphere of each brain was homogenized. Subsamples were obtained from the remaining hemisphere (rostral, caudal, and dorsal cerebral cortices; brainstem, thalamus, and cerebellum). Sodium concentrations of regions and homogenates were measured by inductively coupled plasma–mass spectrometry. Data were analyzed using repeated measures ANOVA with a pairwise post-test to compare mean sodium concentration of each region to mean homogenate sodium concentration. Brain sodium was not uniformly distributed; sodium concentrations in different regions of the same brain varied somewhat unpredictably. Homogenization of an entire brain hemisphere appears to be the ideal method of sample preparation to ensure accurate brain sodium concentration measurement in adult cattle.     

Rectal tears in the horse: malpractice or an unfortunate accident?

Rectal tears are a relatively rare complication of rectal palpation, mating or dystocia, and idiopathic spontaneous occurrence of rectal perforation has also been described. Rectal tears have been classified in a three or a four-grade system. Immediate recognition of the fact that a tear has been made and prompt action will improve the horses chance of survival, and is the best defence of the veterinarian against legislation. There is no clear explanation why rectal tears sometimes occur. A questionnaire of the Netherlands Equine Veterinary Association revealed that rectal tears occurred both to inexperienced veterinarians and to very experienced colleagues, working with or without a probe for ultrasonography. In the opinion of the authors, the approach in the legislation of rectal tears should be that a rectal tear is only considered 'malpractice' if the veterinarian obviously acted carelessly. However, this would create the ridiculous situation that it seems better for the veterinarian-client relationship when the veterinarian confesses to 'careless' rectal palpation. This point needs further clarification, and perhaps an 'insurance of the horse for rectal palpation' will be the solution. Further, retrospectively over the last ten years, the problem is often not 'making a rectal tear', but 'lacking recognition of making a tear'. Whenever a rectal tear is suspected, the veterinarian must assess its severity, discuss the problem openly with the owner and apply appropriate treatment including referral.     

Phosphatidylserine (PS) as a potential nutraceutical for canine brain aging: A review

Neurodegenerative processes are one of the main age-related features of dogs. Senile neurodegeneration can be clinically asymptomatic, “borderline” (i.e., a condition that is intermediate between normal and disease state) or progress toward overt clinical abnormalities, known as age-related cognitive disorders, cognitive dysfunction syndrome (CDS), or senile dementia. The aim of the present article is to review the rationale for the use of phosphatidylserine (PS), a natural phospholipid, in the management of brain neurodegenerative processes in senior dogs. The preliminary clinical data on PS supplementation in senior dogs will also be reviewed. There is evidence that PS is absorbed rapidly, reaches high concentrations in the brain, and is well tolerated. Phosphatidylserine has emerged to exert several in vitro and in vivo neuroprotective activities. It has been shown to positively affect neurotransmitter release and neurotransmitter receptor density in several brain regions from laboratory animals with memory impairments. Phosphatidylserine also was found to revert experimentally-induced amnesia in rats and improve memory deficits both in old animals and in elderly humans with various degrees of cognitive impairment and Alzheimer's dementia. On the basis of the data reported in the scientific literature, PS stands out as an essential “brain nutrient.” In view of these features, some supplements containing PS have been licensed recently as adjuvant treatment for canine and feline brain aging. The results of the studies on its use in the preventative and combined treatment of dogs with clinical features consistent with the diagnosis of CDS are reported. Although PS-based neuroprotection in dogs and cats is still at its infancy, the preliminary collected data look promising and thus merit further investigation.     

Spontaneous Aujeszky's disease (pseudorabies) in European wild boars (Sus scrofa) in the federal state of Brandenburg, Germany

In this report two cases of spontaneous Aujeszky's disease (AD, syn. pseudorabies) in European wild boars (Sus scrofa), in the federal state of Brandenburg, Germany, are described. Both animals displayed severe central nervous disturbances, including loss of fear of humans, disorientation, and tremors of head and limbs, and were shot by hunters for laboratory exclusion of rabies. The main finding in the well nourished, juvenile (approx. 7-8 months) animals was a non-suppurative panencephalitis characterized by neuronal necroses, intranucelar eosinophilic inclusion bodies in necrotic neurons, spongiosis of the neuropil, gliosis and perivascular cuffing of lymphocytes, plasma cells and eosinophilic granulocytes. Pseudorabies virus (PrV)-antigen was detected by immunohistochemistry in typically affected brain areas and was isolated from pooled tissues (brain and tonsil) in both cases. The molecular characterization of the virus isolates revealed that they belonged to the wild boar-associated PrV subtype Iw. These cases indicate that spontaneous AD can sporadically occur in free living wild boars under natural conditions. However, factors triggering the disease, e. g. social stress, age related change from passive to active immunity, individual susceptibility to PrV infection and environmental conditions, have to be clarified by future experimental studies.     

Phenotypic plasticity is maintained despite geographical isolation in an African cichlid fish,Pseudocrenilabrus multicolor

Gene flow among populations in different selective environments should favor the evolution of phenotypic plasticity over local adaptation. Plasticity in development is a common response to long‐term hypoxia in some widespread African fishes, including Pseudocrenilabrus multicolor, a cichlid that exploits both normoxic (high oxygen) rivers/lakes and hypoxic (low oxygen) swamps. Previous studies have shown that fish from normoxic and hypoxic sites differ in many traits, including gill size, brain size and body shape, and that much of this variation reflects developmental plasticity. However, these earlier studies focused on areas in Uganda where gene flow between swamp and river or lake populations is high. In this study we tested the hypothesis that P. multicolor from a relatively isolated lake population (Lake Saka, Uganda) exhibit low levels of plasticity in traits related to oxygen uptake. Multiple broods of P. multicolor from Lake Saka were reared under low and high dissolved oxygen, and traits related to gill size, brain mass and body shape were quantified. Surprisingly, both gill size and brain mass showed high levels of developmental plasticity. We suggest that high levels of plasticity, particularly in the gill size of P. multicolor, reflects low costs of maintaining the plastic response, even in relatively isolated populations.     

MRI characteristics of cerebral microbleeds in four dogs

Cerebral microbleeds in people are small foci of hemosiderin-containing macrophages in normal brain parenchyma. They are the remnant of previous hemorrhage and occur with greater frequency in older individuals. Our purpose was to describe the magnetic resonance (MR) appearance of cerebral microbleeds in four dogs. These lesions appeared as round, hypointense foci measuring ≤4 mm on T2*-gradient-recalled echo images. They were less conspicuous or absent on T2-weighting, being iso- or hypointense, and uniformly invisible on T1-weighted images. No contrast enhancement was seen in any of the cerebral microbleeds. Necropsy-derived histopathologic analysis of one brain confirmed these lesions to be chronic cerebrocortical infarcts containing hemosiderin. The MR changes seen in dogs were analogous to what has been described in people and will be helpful in distinguishing cerebral microbleeds from other brain lesions.     

Infectious cDNA clones of porcine reproductive and respiratory syndrome virus and their potential as vaccine vectors

Full-length infectious cDNA clones have recently become available for both European and North American genotypes of porcine reproductive and respiratory syndrome virus (PRRSV), and it is now possible to alter the PRRSV genome and create genetically defined mutant viruses. Among many possible applications of the PRRSV infectious cDNA clones, development of genetically modified vaccines is of particular interest. Using infectious clones, the PRRSV genome has been manipulated by changing individual amino acids, deleting coding regions, inserting foreign sequences, and generating arterivirus chimeras. The limited available data suggest that all structural proteins of PRRSV are essential for replication of the virus, and that PRRSV infectivity is relatively intolerant of subtle changes within the structural proteins. The major tasks in PRRSV research are to identify virulence factors and pathogenic mechanisms, and to understand the structure-function relationships of individual viral proteins. Utilizing these infectious clones as tools, a new generation of safe and efficacious PRRS vaccines may be constructed.     

Lung lobe torsion in association with a chronic diaphragmatic hernia and haemorrhagic pleural effusion in a cat

CLINICAL SUMMARY: This report describes torsion of the right cranial lung lobe in a cat with haemorrhagic pleural effusion and a chronic diaphragmatic hernia. Surgical treatment comprising lung lobectomy without de-rotation, and repair of the diaphragmatic defect, led to an uneventful recovery. PRACTICAL RELEVANCE: Lung lobe torsion is a rare condition in cats. While spontaneous lung lobe torsions may occur, a frequent association with underlying thoracic disease has been recognised in cats. However, neither haemorrhagic pleural effusion nor diaphragmatic hernia have been previously described in cats with lung lobe torsions, although they have been documented in dogs and humans. In a cat with suspected lung lobe torsion, a thorough search for an underlying disease should be undertaken.