bluuebunny/crossref_metadata_2025_split huggingface dataset:
Avastin as an adjunct to vitrectomy in the management of severe proliferative diabetic retinopathy: a prospective case series
Authors: Yeoh Jonathan , Williams Christopher , Allen Penny , Buttery Robert , Chiu Daniel , Clark Ben , Essex Rohan , McCombe Mark , Qureshi Salmaan , Campbell William G 
Published: July 2008

AbstractPurpose:  Bevacizumab (Avastin) is a monoclonal antibody which targets all isoforms of vascular endothelial growth factor A. Its potent anti‐angiogenic effects have been shown to cause regression of neovascularization in proliferative diabetic retinopathy. The aim of this study is to investigate the role of Avastin as an adjunct to vitrectomy in the management of severe diabetic eye disease.Methods:  Sixteen patients (18 eyes) with severe proliferative diabetic retinopathy were recruited into the study. All eyes underwent a single intravitreal injection of bevacizumab 1.25 mg in 0.05 mL prior to vitrectomy surgery for the management of tractional retinal detachment or vitreous haemorrhage due to severe proliferative diabetic retinopathy.Results:  At 3 months, seven eyes had visual acuities which were better than baseline, four were unchanged and seven were worse. At 6 months, 14 eyes had visual acuities better than baseline, one was unchanged and three were worse. Seven of the 18 eyes (38.8%) had postoperative rebleeds, six of which required surgical washout.Conclusion:  Avastin improved the ease of the surgery in these complex eyes and the early results are encouraging. We have found it to be particularly useful in diabetic eyes with traction detachments of short duration in which there is still active neovascularization.
Network plasticity in cortical assemblies
Authors: Chiappalone Michela , Massobrio Paolo , Martinoia Sergio 
Published: July 2008

AbstractTo investigate distributed synaptic plasticity at the cell assembly level, we used dissociated cortical networks from embryonic rats grown on grids of 60 extracellular substrate‐embedded electrodes (micro‐electrode arrays). We developed a set of experimental plasticity protocols based on the pairing of tetanic bursts (20 Hz) with low‐frequency stimuli (≤ 1 Hz), delivered through two separate channels of the array (i.e. associative tetanic stimulation). We tested our protocols on a large data set of 26 stable cultures, selected on the basis of both their initial level of spontaneous firing and the capability of low‐frequency test stimuli to evoke spikes. Our main results are summarized as follows: (i) low‐frequency stimuli produce neither short‐ nor long‐term changes in the evoked response of the network; (ii) associative tetanic stimulation is able to induce plasticity in terms of a significant increase or decrease of the evoked activity in the whole network; (iii) the amount of change (i.e. increase or decrease of the evoked firing) strongly depends on the specific features of the applied protocols; and (iv) the potentiation induced by a specific associative protocol can last several hours. The results obtained demonstrate that large in vitro cortical assemblies display long‐term network potentiation, a mechanism considered to be involved in the memory formation at cellular level. This pilot study could represent a relevant step towards understanding plastic properties at the neuronal population level.
Retinal transplants restore visual responses: trans‐synaptic tracing from visually responsive sites labels transplant neurons
Authors: Seiler Magdalene J. , Thomas Biju B. , Chen Zhenhai , Wu Rongjuan , Sadda Srinivas R. , Aramant Robert B. 
Published: July 2008

AbstractThis study aimed to test the hypothesis that visual responses in the superior colliculus (SC) originate from synaptic connections between fetal retinal transplants and degenerating host retinas. Sheets of embryonic day 19 rat retina expressing human placental alkaline phosphatase were transplanted to the subretinal space of 3‐ to 4‐week‐old S334ter‐line‐3 rats with fast retinal degeneration. Several months later, visual responses were recorded from the SC. Attenuated pseudorabies virus that is specifically transferred between neurons at synapses (strains PRV‐152, expressing green fluorescent protein (GFP) or BaBlu, expressing Escherichia coliβ‐galactosidase) was injected into the visually responsive site of the SC. After survival times of 1–2 days, the virus was detected in the retina by immunohistochemistry in combination with different retinal cell markers, such as protein kinase C, recoverin, calcium‐calmodulin‐dependent protein kinase II and glutamine synthetase. Transplanted rats had a mean response threshold of −3.1 log cd/m2 in a small area of the SC corresponding to the location of the graft in the retina. By 30 h after injection into this SC area, the virus traced back to host ganglion cells overlying the transplant and in close proximity to the transplant. By 2 days after injection, extensive virus label was found in the host retina and many cells in the transplant were also labeled. Virus‐labeled cells in the transplant were double labeled for neuronal and glial cell markers. This study provides anatomical evidence that synaptic connections between fetal retinal transplants and host retinas contribute to the visual responses in the SC.
Effects of corticosterone on corticotrophin‐releasing hormone and gastrin‐releasing peptide release in response to an aversive stimulus in two regions of the forebrain (central nucleus of the amygdala and prefrontal cortex)
Authors: Merali Zul , Anisman Hymie , James Jonathan S. , Kent Pam , Schulkin Jay 
Published: July 2008

AbstractPrevious research has shown that chronic corticosterone treatment increases the expression of corticotrophin‐releasing hormone (CRH) mRNA at the central nucleus of the amygdala (CeA). Like CRH, gastrin‐releasing peptide (GRP) appears to be involved in mediation of the stress response and is released at the CeA during exposure to an acute stressor. Using in‐vivo microdialysis, this study examined the effects of corticosterone treatment on the release of CRH and GRP in response to an airpuff challenge at two forebrain regions, the CeA and medial prefrontal cortex. Adrenally intact rats were treated with corticosterone by systemic implants over a 14‐day period prior to microdialysis probe insertion. We found that, at both regions, the airpuff‐induced CRH and GRP release were enhanced in the corticosterone pellet‐implanted rats as compared with the release observed in the vehicle‐implanted control rats. These findings suggest that chronic corticosterone exposure potentiates the stressor‐elicited release of CRH and GRP. As cortisol dysregulation has frequently been reported in people with psychiatric conditions, such as anxiety disorders or depression, a better understanding of the glucocorticoid‐mediating regulation of CRH and GRP may provide insight into the underlying neurochemical mechanisms involved in both adaptive fear‐type responses and maladaptive responses leading to pathology.
Regulation of ASIC activity by ASIC4 – new insights into ASIC channel function revealed by a yeast two‐hybrid assay
Authors: Donier Emmanuelle , Rugiero François , Jacob Céline , Wood John N. 
Published: July 2008

AbstractASIC4 is a member of the acid‐sensing ion channel family that is broadly expressed in the mammalian nervous system, but has no known function. We demonstrate here that transfected ASIC4 is targeted to the plasma membrane in CHO‐K1 cells, where it associates with ASIC1a and downregulates exogenous ASIC1a expression. This effect could also be observed on endogenous H+‐gated currents in TSA‐201 cells and ASIC3 currents in CHO‐K1 cells, suggesting a physiological role for ASIC4 in regulating ASIC currents involved in pain mechanisms. Using a yeast two‐hybrid assay we found that ASICs interact with proteins involved in diverse functions, including cytoskeletal proteins, enzymes, regulators of endocytosis and G‐protein‐coupled pathways. ASIC4 is the sole member of this ion channel class to interact strongly with polyubiquitin. The distinct functionally related sets of interacting proteins that bind individual ASICs identified in the yeast two‐hybrid screen suggest potential roles for ASICs in a variety of cellular functions.
Size variation and cell proliferation in chemosensory brain areas of a lizard (Podarcis hispanica): effects of sex and season
Authors: Sampedro Carlos , Font Enrique , Desfilis Ester 
Published: July 2008

AbstractMany lizards rely on chemoreception for crucial aspects of their biology, including exploration, prey and predator detection, and intraspecific communication. Here we investigate sex and seasonal variation in size and proliferative activity in chemosensory areas of the lizard brain. We captured adult Iberian wall lizards (Podarcis hispanica) of either sex in the breeding (April) and non‐breeding (November) season, injected them with 5‐bromo‐2′‐deoxyuridine (BrdU) and killed them 3 weeks later. We removed the brains, measured the length of the olfactory bulbs, and counted BrdU‐labelled cells in the main and accessory olfactory bulbs (MOB, AOB), lateral cortex (LC) and nucleus sphericus (NS). Our results show that, relative to body size, males have larger MOBs and AOBs than females; however, relative to brain size, males have larger AOBs, but not larger MOBs than females. Additionally, males produce more new cells than females in the olfactory bulbs, LC and NS. We failed to detect significant seasonal changes or sex × season interaction in size or proliferative activity in these areas. Sex differences in the addition of newly generated cells – mainly neurons – may be partly responsible for the size differences in chemosensory brain areas. The presence of sexual dimorphism in AOB is expected given the available behavioural evidence, which suggests that males of P. hispanica are more responsive than females to socially relevant chemical stimuli. This is the first demonstration of sexual dimorphism in size and proliferative activity in chemosensory areas of a non‐mammalian species.
Multiple cerebellar zones are involved in the control of individual muscles: a retrograde transneuronal tracing study with rabies virus in the rat
Authors: Ruigrok Tom J. H. , Pijpers Angelique , Goedknegt‐Sabel Erika , Coulon Patrice 
Published: July 2008

AbstractTo identify cerebellar regions that are involved in the control of limb muscles, rabies virus was injected into the tibialis anterior (TA), the gastrocnemius (GC) or, for comparison, into the flexor digitorum (FD) muscles of the rat. Progression of retrograde transneuronal infection at supraspinal levels was assessed after variable time spans and was divided into three groups. Initially, infected neurons were observed in the reticular formation, lateral vestibular nucleus, red nucleus and motor cortex (group 1). Group 2 was characterized by labelling within the cerebellar nuclei as well as of two vermal strips of Purkinje cells (PCs). Double‐labelling with zebrin enabled identification of these strips as the lateral part of the A1‐ and B‐zone. For TA both zones were ipsilateral, whereas for GC the A1 strip predominated contralaterally. Group 3 infections showed additional labelling of multiple, in part bilateral, identifiable strips of PCs in vermis, paravermis and hemisphere. FD injections resulted in less robust labelling of vermal strips and more pronounced labelling within paravermal and hemispheral zonal regions. Only sporadic labelling in corresponding regions of the inferior olive and no labelling of cortical interneurons or granule cells was observed. Prolonged infection was seen to result in degeneration of PCs and possibly of motoneurons. We conclude that vermal, paravermal as well as hemispheral zones of the cerebellar cortex converge upon motoneurons that innervate a particular muscle. In addition, individual zones may control motorpools of different muscles and thus contribute to muscle synergies.
Spatial and temporal sensitivity degradation of primary visual cortical cells in senescent rhesus monkeys
Authors: Zhang Jie , Wang Xiusong , Wang Yongchang , Fu Yu , Liang Zhen , Ma Yuanye , Leventhal Audie G. 
Published: July 2008

AbstractHuman visual function declines with age. Much of this decline is mediated by changes in the central visual pathways. In this study we compared the spatial and temporal sensitivities of striate cortical cells in young and old paralysed macaque monkeys. Extracellular single‐unit recordings were employed. Our results show that cortical neurons in old monkeys exhibit lower optimal spatial and temporal frequencies, lower spatial resolution and lower high temporal frequency cut‐offs than do cells in young adult monkeys. These changes in old monkeys are accompanied by increased visually evoked responses, increased spontaneous activities and decreased signal‐to‐noise ratios. The increased excitability of cells in old animals is consistent with an age‐related degeneration of intracortical inhibition. The degradation of spatial and temporal function in old striate cortex should contribute to the decline in visual function that accompanies normal aging.
Sex differences in cell proliferation and glucocorticoid responsiveness in the zebra finch brain
Authors: Katz Amnon , Mirzatoni Anahid , Zhen Yin , Schlinger Barney A. 
Published: July 2008

AbstractNeural proliferation is a conserved property of the adult vertebrate brain. In mammals, stress reduces hippocampal neuronal proliferation and the effect is stronger in males than in females. We tested the effects of glucocorticoids on ventricular zone cell proliferation in adult zebra finches where neurons are produced that migrate to and incorporate within the neural circuits controlling song learning and performance. Adult male zebra finches sing and have an enlarged song circuitry; females do not sing and the song circuit is poorly developed. Freshly prepared slices from adult males and females containing the lateral ventricles were incubated with the mitotic marker BrdU with or without steroid treatments. BrdU‐labeled cells were revealed immunocytochemically and all labeled cells within the ventricular zone were counted. We identified significantly higher rates of proliferation along the ventricular zone of males than in females. Moreover, acute administration of corticosterone significantly reduced proliferation in males with no effects in females. This effect in males was replicated by RU‐486, which appears to act as an agonist of the glucocorticoid receptor in the songbird brain. The corticosterone effect was reversed by Thiram, which disrupts corticosterone action on the glucocorticoid receptor. Sex differences in proliferation and responses to stress hormones may contribute to the sexually dimorphic and seasonal growth of the neural song system of songbirds.
Gene inactivation of Na+/H+ exchanger isoform 1 attenuates apoptosis and mitochondrial damage following transient focal cerebral ischemia
Authors: Wang Yanping , Luo Jing , Chen Xinzhi , Chen Hai , Cramer Sam W. , Sun Dandan 
Published: July 2008

AbstractWe investigated mechanisms underlying the Na+/H+ exchanger isoform 1 (NHE1)‐mediated neuronal damage in transient focal ischemia. Physiological parameters, body and tympanic temperatures, and regional cerebral blood flow during 30 min of middle cerebral artery occlusion were similar in wild‐type NHE1 (NHE1+/+) and NHE1 heterozygous (NHE1+/−) mice. NHE1+/+ mice developed infarct volume of 57.3 ± 8.8 mm3 at 24 h reperfusion (Rp), which progressed to 86.1 ± 10.0 mm3 at 72 h Rp. This delayed cell death was preceded by release of mitochondrial cytochrome c (Cyt. C), nuclear translocation of apoptosis‐inducing factor (AIF), activation of caspase‐3, and TUNEL‐positive staining and chromatin condensation in the ipsilateral hemispheres of NHE1+/+ brains. In contrast, NHE1+/− mice had a significantly smaller infarct volume and improved neurological function. A similar neuroprotection was obtained with NHE1 inhibitor HOE 642. The number of apoptotic cells, release of AIF and Cyt. C or levels of active caspase‐3 was significantly reduced in NHE1+/− brains. These data imply that NHE1 activity may contribute to ischemic apoptosis. Ischemic brains did not exhibit changes of NHE1 protein expression. In contrast, up‐regulation of NHE1 expression was found in NHE1+/+ neurons after in vitro ischemia. These data suggest that NHE1 activation following cerebral ischemia contributes to mitochondrial damage and ischemic apoptosis.
Behavioural profile of a new mouse model for NPY deficiency
Authors: Karl Tim , Duffy Liesl , Herzog Herbert 
Published: July 2008

AbstractThe abundantly expressed neuropeptide Y (NPY) plays an important role in anxiety and stress reactivity, as exogenous NPY administration reduces anxiety‐like behaviour in rodents. However, unlike the potent effects of NPY seen in pharmacological studies, two independent examinations of a genetic mouse model for NPY deficiency have shown only subtle, inconsistent and task‐dependent anxiety‐related phenotypes for male mutants. Here we present results of a newly developed germline NPY‐knockout model, which has been characterized behaviourally using a comprehensive multi‐tiered phenotyping strategy. Mice of both sexes were investigated in locomotion and exploration tasks, anxiety‐related paradigms, a hippocampus‐dependent memory test and a battery of basic tasks screening for sensory and motor functions. Male and female NPY‐deficient mice consistently demonstrated suppressed levels of locomotion and exploration. Furthermore, mutant mice exhibited a pronounced anxiogenic‐like phenotype when tested in spatiotemporal anxiety‐relevant paradigms (i.e. elevated‐plus maze, open field and light–dark task). Importantly, this phenotype was more pronounced in male NPY mutants, revealing a moderate sexually dimorphic impact of NPY deficiency on behaviour. Interestingly, lack of NPY did not result in impaired learning and memory in either sex. Our carefully selected comprehensive behavioural phenotyping strategy revealed a consistent hypolocomotive and sex‐dependent anxious‐like phenotype. This new NPY‐knockout mouse model reveals the importance of sex‐specific testing. It also offers a potent new model for research into anxiety‐related disorders and suggests potential treatment options for these conditions via the NPY system.
GDNF hyperalgesia is mediated by PLCγ, MAPK/ERK, PI3K, CDK5 and Src family kinase signaling and dependent on the IB4‐binding protein versican
Authors: Bogen Oliver , Joseph Elizabeth K. , Chen Xiaojie , Levine Jon D. 
Published: July 2008

AbstractThe function of the isolectin B4 (IB4+)‐binding and GDNF‐dependent Ret (Ret+)‐expressing non‐peptidergic subpopulation of nociceptors remain poorly understood. We demonstrate that acute administration of GDNF sensitizes nociceptors and produces mechanical hyperalgesia in the rat. Intrathecal IB4–saporin, a selective toxin for IB4+/Ret+‐nociceptors, attenuates GDNF but not NGF hyperalgesia. Conversely, intrathecal antisense to Trk A attenuated NGF but not GDNF hyperalgesia. Intrathecal administration of antisense oligodeoxynucleotides targeting mRNA for versican, the molecule that renders the Ret‐expressing nociceptors IB4‐positive (+), also attenuated GDNF but not NGF hyperalgesia, as did ADAMTS‐4, a matrix metalloprotease known to degrade versican. Finally, inhibitors for all five signaling pathways known to be activated by GDNF at GFRα1/Ret: PLCγ, CDK5, PI3K, MAPK/ERK and Src family kinases, attenuated GDNF hyperalgesia. Our results demonstrate a role of the non‐peptidergic nociceptors in pain produced by the neurotrophin GDNF and suggest that the IB4‐binding protein versican functions in the expression of this phenotype.
The nitric oxide/cyclic guanosine monophosphate pathway modulates the inspiratory‐related activity of hypoglossal motoneurons in the adult rat
Authors: Montero Fernando , Portillo Federico , González‐Forero David , Moreno‐López Bernardo 
Published: July 2008

AbstractMotoneurons integrate interneuronal activity into commands for skeletal muscle contraction and relaxation to perform motor actions. Hypoglossal motoneurons (HMNs) are involved in essential motor functions such as breathing, mastication, swallowing and phonation. We have investigated the role of the gaseous molecule nitric oxide (NO) in the regulation of the inspiratory‐related activity of HMNs in order to further understand how neural activity is transformed into motor activity. In adult rats, we observed nitrergic fibers and bouton‐like structures in close proximity to motoneurons, which normally lack the molecular machinery to synthesize NO. In addition, immunohistochemistry studies demonstrated that perfusion of animals with a NO donor resulted in an increase in the levels of cyclic guanosine monophosphate (cGMP) in motoneurons, which express the soluble guanylyl cyclase (sGC) in the hypoglossal nucleus. Modulators of the NO/cGMP pathway were micro‐iontophoretically applied while performing single‐unit extracellular recordings in the adult decerebrated rat. Application of a NO synthase inhibitor or a sGC inhibitor induced a statistically significant reduction in the inspiratory‐related activity of HMNs. However, excitatory effects were observed by ejection of a NO donor or a cell‐permeable analogue of cGMP. In slice preparations, application to the bath of a NO donor evoked membrane depolarization and a decrease in rheobase, which were prevented by co‐addition to the bath of a sGC inhibitor. These effects were not prevented by reduction of the spontaneous synaptic activity. We conclude that NO from afferent fibers anterogradely modulates the inspiratory‐related activity of HMNs by a cGMP‐dependent mechanism in physiological conditions.
EGb761 protects against nigrostriatal dopaminergic neurotoxicity in 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine‐induced Parkinsonism in mice: role of oxidative stress
Authors: Rojas Patricia , Serrano‐García Norma , Mares‐Sámano José J. , Medina‐Campos Omar Noel , Pedraza‐Chaverri José , Ögren Sven Ove 
Published: July 2008

Abstract1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP) causes nigrostriatal dopaminergic neurotoxicity and behavioral impairment in rodents. Previous studies suggest that oxidative stress, via free radical production, is involved in MPTP‐induced neurotoxicity. The MPTP‐treated mouse has been the most widely used model for assessing neuroprotective agents for Parkinson’s disease. It has been reported previously that EGb761 prevents dopaminergic neurotoxicity of MPTP. This compound is multifunctional via different mechanisms. Here, we report the neuroprotective effect of EGb761 against oxidative stress induced by MPTP in C57BL/6J mice. EGb761 is a patented and well‐defined mixture of active compounds extracted from Ginkgo biloba leaves, with neuroprotective effects, exerted probably via its antioxidant or free radical scavenger action. MPTP administration resulted in a significant decrease in striatal dopamine levels and tyrosine hydroxylase immunostaining in the striatum and substantia nigra pars compacta. Mice receiving EGb761 had significantly attenuated MPTP‐induced loss of striatal dopamine levels and tyrosine hydroxylase immunostaining in the striatum and substantia nigra pars compacta. The neuroprotective effect of EGb761 against MPTP neurotoxicity is associated with blockade of lipid peroxidation and reduction of superoxide radical production (indicated by a down‐regulation of Mn‐superoxide dismutase activity), both of which are indices of oxidative stress. Behavioral analyses showed that EGb761 improved MPTP‐induced impairment of locomotion in a manner that correlated with enhancement of striatal dopamine levels. These findings suggest that, in mice, EGb761 attenuates MPTP‐induced neurodegeneration of the nigrostriatal pathway and that an inhibitory effect against oxidative stress may be partly responsible for its observed neuroprotective effects.