Tamir Ben-Hur's scientific contributionswhile working at Hadassah Medical Center (Jerusalem, Israel) and other institutions

Publications (185)

Publications citing this author (7661)

    • Furthermore, NSC-induced increases in activated CD11b + microglia have been shown to lead to IGF-1, VEGF, transforming growth factor (TGF)-β, and brain-derived neurotrophic factor (BDNF) production, yielding better motor function and axonal sprouting; such findings again speak to the dynamic/context dependent nature of inflammation/inflammatory cells (Capone et al., 2007, Daadi et al., 2010, Lalancette-Hebert et al., 2007). Beyond the CNS systemically delivered NSCs can also be found within secondary lymphoid organs where they serve to modulate inflammation (Einstein et al., 2007, Lee et al., 2008b, Pluchino et al., 2009a, Pluchino et al., 2009b). In lymph nodes, the increased bioavailability of BMP-4, BMP-7, sonic hedgehog (Shh) and Noggin, released by both transplanted NSCs and immune cells, promotes the survival and persistence of grafted NSCs outside the CNS, at the levels of ectopic perivascular germinal niche-like lymph node areas (Pluchino et al., 2009b).
    [Show abstract] [Hide abstract] ABSTRACT: There exists an urgent need for effective treatments for those patients suffering from chronic/progressive multiple sclerosis (MS). Accordingly, it has become readily apparent that different classes of stem cell-based therapies must be explored at both the basic science and clinical levels. Herein, we provide an overview of the basic mechanisms underlying the pre-clinical benefits of exogenously delivered non-hematopoietic stem cells (nHSCs) in animal models of MS. Further, we highlight a number of early clinical trials in which nHSCs have been used to treat MS. Finally, we identify a series of challenges that must be met and ultimately overcome if such promising therapeutics are to be advanced from the bench to the bedside.
    Full-text · Article · Dec 2016
    • There seems to be a factor in the makeup of strain KM322 which restrains its inherent rabbit neurovirulence and which can also restrain co-inoculated neuroinvasive KM91. Although short specific HSV DNA sequences have recently been shown to control neurovirulence in mice and tree shrews (Rosen et al., 1986) the nature and function of the gene(s) involved are still unknown. Further studies are now in progress to identify the genes responsible for the neurovirulence of aHVS KM91 and for the virulence restraint operated on it by strain KM322 for rabbits and to examine the immunobiology of aHVS in general.
    [Show abstract] [Hide abstract] ABSTRACT: One (KM91) of a series of isolates of alphaherpesvirus saimiri (alpha HVS) produced rapidly fatal encephalitis in rabbits following intradermal infection, whereas the others (KM180, KM322 and KM338) were non-lethal and produced ganglionitis and prolonged latency. Alphaherpesvirus saimiri KM91 initially produced ganglionitis but quickly ascended the spinal cord to the brain causing death 10 days post-infection. Prior infection with any of the three benign isolates or inoculation with beta-propiolactone (beta PL)-inactivated alpha HVS KM91 protected rabbits from lethal encephalitis when they were subsequently challenged with a lethal dose of alpha HVS KM91. Each of 20 rabbits co-inoculated in the same site with a lethal dose of alpha HVS KM91 and either alpha HVS KM322 (1.5 X 10(3) to 1.5 X 10(5) p.f.u.) or beta PL-inactivated alpha HVS KM322 (1 X 10(7) p.f.u. equivalents) survived. In contrast only half of those co-inoculated with alpha HVS KM91 and beta PL-inactivated alpha HVS KM91 (1 X 10(7) p.f.u. equivalents) survived. Co-inoculation of lethal alpha HVS KM91 (75 p.f.u.) and benign alpha HVS KM322 (1.5 X 10(3) p.f.u.) into opposite flanks resulted in protection from encephalitis in one of four rabbits. Alphaherpesvirus saimiri KM91 was shown to have the capacity to become latent in dorsal root ganglia if the rabbit did not die.
    Full-text · Article · Aug 1988
    • The absence of causes other than migraine does not necessarily imply that migraine is the cause, given that about half of the ischemic strokes in young adults have no detectable cause. According to large series, the incidence of migrainous infarction1718192021 varies between 0.5 and 1.5% of all ischemic strokes and 10 and 14% of ischemic strokes in young patients. The clinical features typifying migrainous stroke included female sex, mean age in the low-to-mid-30 s, a history of cigarette smoking, and ischemic involvement of the PCA territory [19].
    [Show abstract] [Hide abstract] ABSTRACT: In spite of the strong epidemiologic evidence linking migraine and ischemic stroke in young adults, the mechanisms explaining this association remain poorly understood. The observation that stroke occurs more frequently during the interictal phase of migraine prompts to speculation that an indirect relation between the two diseases might exist. In this regard, four major issues might be considered which may be summarized as follows: (1) the migraine-ischemic stroke relation is influenced by specific risk factors such as patent foramen ovale or endothelial dysfunction and more frequent in particular conditions like spontaneous cervical artery dissection; (2) migraine is associated with an increased prevalence of cardiovascular risk factors; (3) the link is caused by migraine-specific drugs; (4) migraine and ischemic vascular events are linked via a genetic component. In the present paper, we will review epidemiological studies, discuss potential mechanisms of migraine-induced stroke and comorbid ischemic stroke, and pose new research questions.
    Full-text · Article · Dec 2010
    • However, ammonia levels were only slightly elevated, and all other routine laboratory parameters were entirely normal. Moreover, plasma carnitine was in the normal range, thus excluding hypocarnitinemia as an underlying pathology as previously suggested (Averbuch-Heller et al., 1994; Verrotti et al., 2002). VPA serum concentrations were in the upper normal range, thus hepatic encephalopathy as well as VPA intoxication cannot explain EEG abnormalities and neurologic symptoms.
    [Show abstract] [Hide abstract] ABSTRACT: In recent years, the use of valproic acid (VPA) as a mood-stabilizing agent has continuously increased. Although VPA usually is well tolerated, its use in combination with other psychotropic compounds might bear an elevated risk of adverse reactions. Here, we present the case of a 42-year-old male suffering from treatment-resistant psychotic depression, who was prescribed VPA additionally to lithium, clomipramine, flupentixol and risperidone. By doing so, he developed myoclonus, tremor and encephalopathy with sedation and marked EEG background slowing. Most notably, these side effects occurred in the presence of normal VPA and ammonia serum concentrations. On VPA discontinuation, all symptoms vanished and EEG normalized. We thus suggest that direct VPA-induced encephalopathy in the absence of ammonemia does exist, in this case probably facilitated by psychotropic polypharmacy.
    Full-text · Article · Oct 2004
    • An excellent review on mice " templating " can be found in (Dorr et al., 2008), with more recent efforts in (Ma et al., 2008; Aggarwal et al., 2009; Chuang et al., 2011; Hawrylycz et al., 2011). However, in spite of the recent uprising of rat models of epilepsy (Tenney et al., 2003; Nersesyan et al., 2004; David et al., 2008; Englot et al., 2008), Parkinson (Van Camp et al., 2003; Pelled et al., 2005; Hou et al., 2010), autism (Pletnikov et al., 2001; Osumi, 2009), Alzheimer (Ganten, 1998; Yang et al., 2011), stroke (Li et al., 2000; Aoki et al., 2003), spinal cord injury (Ramu et al., 2006; Endo et al., 2007; Takagi et al., 2009; Ghosh et al., 2010 ), depression (Huang et al., 2011), among others, there is less focus on the construction of rat templates and either discrete or probabilistic digitalizations of tissues or structures. In fact, although there have been different approaches (Toga et al., 1995; Leergaard et al., 2003; Keilholz et al., 2006; Hjornevik et al., 2007), only two papers have provided rat MRI template sets with average reference images, tissue segmentations, or discrete parcellations (Schweinhardt et al., 2003; Schwarz et al., 2006).
    [Show abstract] [Hide abstract] ABSTRACT: Over the last decade, several papers have focused on the construction of highly detailed mouse high field magnetic resonance image (MRI) templates via non-linear registration to unbiased reference spaces, allowing for a variety of neuroimaging applications such as robust morphometric analyses. However, work in rats has only provided medium field MRI averages based on linear registration to biased spaces with the sole purpose of approximate functional MRI (fMRI) localization. This precludes any morphometric analysis in spite of the need of exploring in detail the neuroanatomical substrates of diseases in a recent advent of rat models. In this paper we present a new in vivo rat T2 MRI template set, comprising average images of both intensity and shape, obtained via non-linear registration. Also, unlike previous rat template sets, we include white and gray matter probabilistic segmentations, expanding its use to those applications demanding prior-based tissue segmentation, e.g., statistical parametric mapping (SPM) voxel-based morphometry. We also provide a preliminary digitalization of latest Paxinos and Watson atlas for anatomical and functional interpretations within the cerebral cortex. We confirmed that, like with previous templates, forepaw and hindpaw fMRI activations can be correctly localized in the expected atlas structure. To exemplify the use of our new MRI template set, were reported the volumes of brain tissues and cortical structures and probed their relationships with ontogenetic development. Other in vivo applications in the near future can be tensor-, deformation-, or voxel-based morphometry, morphological connectivity, and diffusion tensor-based anatomical connectivity. Our template set, freely available through the SPM extension website, could be an important tool for future longitudinal and/or functional extensive preclinical studies.
    Full-text · Article · Nov 2011
    • There is a substantial body of evidence demonstrating the beneficial effect of neural cell-based therapies in experimental autoimmune encephalomyelitis (EAE) and other animal models of demyelinating disease. Seminal studies by two groups utilizing EAE mouse models revealed the potential of mouse neural precursor cells (NPCs) to attenuate inflammation and promote CNS repair164165166167168, with later studies confirming neural cells derived from ESCs could also exert a therapeutic effect169170171. Perhaps not surprisingly, the inflammatory microenvironment within the CNS of EAE mice appears to exert a major influence on the fate of transplanted cells, which remain in an immature state and act through immune modulation and neuroprotection when transplanted at a time of active neuroinflammation, but may be more likely to undergo differentiation when administered during chronic disease when neurodegenerative mechanisms predomi- nate [165,172173174 .
    [Show abstract] [Hide abstract] ABSTRACT: The advent of human induced pluripotent stem cells (hiPSCs), reprogrammed in vitro from both healthy and disease-state human somatic cells, has triggered an enormous global research effort to realize personalized regenerative medicine for numerous degenerative conditions. hiPSCs have been generated from cells of many tissue types and can be differentiated in vitro to most somatic lineages, not only for the establishment of disease models that can be utilized as novel drug screening platforms and to study the molecular and cellular processes leading to degeneration, but also for the in vivo cell-based repair or modulation of a patient's disease profile. hiPSCs derived from patients with the neurodegenerative diseases amyotrophic lateral sclerosis, Parkinson's disease, Alzheimer's disease and multiple sclerosis have been successfully differentiated in vitro into disease-relevant cell types, including motor neurons, dopaminergic neurons and oligodendrocytes. However, the generation of functional iPSC-derived neural cells that are capable of engraftment in humans and the identification of robust disease phenotypes for modeling neurodegeneration still require a number of key challenges to be addressed. Here, we discuss these challenges and summarize recent progress towards the application of iPSC technology for these four common neurodegenerative diseases.
    Full-text · Article · May 2014
    • In the healthy brain, MMP-2/9 modulate neural progenitor cell migration from the SVZ to the olfactory bulb along the rostral migratory stream (Bovetti et al., 2007), whereas following brain lesions, MMP-2/ 9 participate on migration of neural progenitors into an injured area. Besides migration, MMPs play regulatory activity in different tissues, processing active molecules as surface receptors, growth factors and chemokines (Ben-Hur et al., 2006;Kang et al., 2008;Lee et al., 2006). CXCL12 is one of the many substrates of MMP-2/9, and cleavage in a specific site at N-terminal portion of CXCL12 generates CXCL12(5-67) (McQuibban et al., 2001).
    [Show abstract] [Hide abstract] ABSTRACT: The subventricular zone (SVZ) of the adult mammalian brain hosts full potential neural stem cells (NSCs). NSCs are able to respond to extracellular signals in the brain, amplifying the pool of progenitor cells and giving rise to neuroblasts that show ability to migrate towards an injury site. These signals can come from vascular system, cerebrospinal fluid, glial cells, or projections of neurons in adjoining regions. CXCL12, a chemokine secreted after brain injury, reaches the SVZ in a gradient manner and drives neuroblasts towards the lesion area. Among many other molecules, matrix metalloproteinase 2 and 9 (MMP-2/9) are also released during brain injury. MMP-2/9 can cleave CXCL12 generating a new molecule, CXCL12(5-67), and its effects on NSCs viability is not well described. Here we produced recombinant CXCL12 and CXCL12(5-67) and evaluated their effect in murine adult NSCs migration and survival in vitro. We showed CXCL12(5-67) does not promote NSCs migration, but does induce cell death. The NSC death induced by CXCL12(5-67) involves caspases 9 and 3/7 activation, implying the intrinsic apoptotic pathway in this phenomenon. Our evidences in vitro make CXCL12(5-67) and its receptor potential candidates for brain injuries and neurodegeneration studies.
    Full-text · Article · Jun 2017
    • Pomimo mo¿liwego zwi¹zku przyczynowego opisywanego zaka¿enia z ZGB, wydaje siê, ¿e u chorych z za paln¹ polineuropati¹ nie ma koniecznooeci przeprowadzenia rutynowej diagnostyki w kierunku zaka¿enia HAV, po niewa¿: zwi¹ zek ten jest sporadyczny, pierwsze symptomy ZGB pojawiaj¹ siê zazwyczaj po wyst¹pieniu klinicznych objawów ostrego zapalenia w¹troby, a udokumentowanie wspó³istnienia zaka¿enia HAV i neuropatii nie ma wartooeci prognostycznej ani implikacji terapeu- tycznych [1]. Istniej¹ doniesienia o wystêpowaniu u chorych z ostrym zaka¿eniem HAV mnogiej mononeuropatii nerwu okoruchowego i twarzowego [13] , jak równie¿ nerwu ³okciowego i skórnego uda bocznego [14] . Ponadto kazuistycznie obserwowano czuciow¹ mononeuropatiê nerwu trójdzielnego [15] , mononeuropatiê nerwu twa- rzowego [16] oraz czuciow¹ neuropatiê objawiaj¹c¹ siê ostrym jednostronnym ubytkiem czucia w za kresie dermatomów Th12-S1 w prodromalnej fazie serologicznie potwierdzonego WZW typu A [17] .
    [Show abstract] [Hide abstract] ABSTRACT: Wirusy pierwotnie hepatotropowe, poza dysfunkcją wątroby, mogą powodować zmiany patologiczne innych narządów i układów, w tym także obwodowego układu nerwowego. Patogeneza powikłań neurologicznych w przebiegu zakażeń wirusami zapaleń wątroby nie jest do końca poznana i jednoznaczna. Wydaje się celowe, by u pacjentów z potwierdzoną w badaniach laboratoryjnych nieprawidłową funkcją wątroby i współwystępującymi objawami ze strony obwodowego układu nerwowego, zwłaszcza w postaci zespołu Guillaina–Barrégo, mononeuropatii, mononeuropatii mnogiej czy polineuropatii, rozważyć diagnostykę w kierunku zakażeń wirusami pierwotnie hepatotropowymi. Dotąd nie ustalono jednoznacznych strategii leczenia neurologicznych manifestacji zakażeń wirusami hepatotropowymi, co powoduje, że postępowanie terapeutyczne w każdym przypadku jest indywidualne. W pracy na podstawie dostępnego piśmiennictwa omówiono neuropatie obwodowe towarzyszące zakażeniom wirusami zapaleń wątroby typu A, B, C oraz E.
    Full-text · Article · Dec 2012
    • First, unspecific symptoms like heaviness of the legs, tiredness, or cramps may not be taken as seriously in women compared to men. We know from other studies that symptoms such as fatigability are more often attributed to psychological problems in women than in men [14,15]. Also, men are physically more active and therefore might be more quickly aware of physical problems.
    [Show abstract] [Hide abstract] ABSTRACT: New therapeutic strategies in muscular dystrophies will make a difference in prognosis only if they are begun early in the course of the disease. Therefore, we investigated factors that influence the time to diagnosis in muscle dystrophy patients. A sample of 101 patients (mean age 49 years; range 19-80; 44% women) with diagnosed muscle dystrophies from neurological practices and the neuromuscular specialty clinic in Berlin, Germany, was invited to participate. Time from first consultation to diagnosis, subspecialty of physician, and sociodemographic data were assessed with self-report questionnaires. The association between time to diagnosis and potential predictors (subspecialty of initially consulted physician, diagnoses, gender, and age at onset) was modeled with linear regression analysis. The mean time span between first health-care contact and diagnosis was 4.3 years (median 1). The diagnostic delay was significantly longer if patients were initially seen by a non-neurological specialist compared to a general practitioner (5.2 vs. 3.5 years, p = 0.047). Other factors that were independently associated with diagnostic delay were female gender and inherited muscle disease. Action to improve clinical awareness of muscle diseases in non-neurological specialists is needed.
    Full-text · Article · May 2011
    • Repair of myelin by endogenous cells is a wellestablished phenomenon in the dorsal columns of the spinal cord and non-myelinating and/or de-differentiated SCs migrating from the dorsal roots are generally considered to contribute to this (Beattie et al., 1997; Duncan and Hoffman, 1997; Nagoshi et al., 2011). However, there is also evidence that precursor cells present within the CNS can give rise to remyelinating SCs (Akiyama et al., 2001; Blakemore, 2005; Keirstead et al., 1999; Zawadzka et al., 2010). At present the relative contribution of each of these potential sources of SCs is uncertain.
    [Show abstract] [Hide abstract] ABSTRACT: Autologous cell transplantation is a promising strategy for repair of the injured spinal cord. Here we have studied the repair potential of mesenchymal stromal cells isolated from the human olfactory mucosa after transplantation into a rodent model of incomplete spinal cord injury. Investigation of peripheral type remyelination at the injury site using immunocytochemistry for P0, showed a more extensive distribution in transplanted compared with control animals. In addition to the typical distribution in the dorsal columns (common to all animals), in transplanted animals only, P0 immunolabelling was consistently detected in white matter lateral and ventral to the injury site. Transplanted animals also showed reduced cavitation. Several functional outcome measures including end-point electrophysiological testing of dorsal column conduction and weekly behavioural testing of BBB, weight bearing and pain, showed no difference between transplanted and control animals. However, gait analysis revealed an earlier recovery of co-ordination between forelimb and hindlimb stepping in transplanted animals. This improvement in gait may be associated with the enhanced myelination in ventral and lateral white matter, where fibre tracts important for locomotion reside. Autologous transplantation of mesenchymal stromal cells from the olfactory mucosa may therefore be therapeutically beneficial in the treatment of spinal cord injury. GLIA 2017
    Full-text · Article · Feb 2017
    • Several viral genes have been shown to determine HSV-1 virulence for experimental animals. These genes enable the virus to overcome host defense systems (Ben-Hur et al., 1988), to invade the nervous system (Izumi and Stevens, 1990) and to induce lethal encephalitis (Ben-Hur et al., 1987; Chou et al., 1990). We have previously reported on an intratypic HSV-1 recombinant virus strain, termed R-15 that was avirulent to mice and rats by various routes of inoculation , including direct intracranial inoculation (Ben-Hur et al., 1987).
    [Show abstract] [Hide abstract] ABSTRACT: We examined whether immunization with the nonpathogenic strain R-15 of herpes simplex virus-1 (HSV-1) may prevent the clinical and neuroendocrine changes induced by the pathogenic HSV-1 strain Syn17+. Inoculation of strain Syn17+ to control rats induced fever, marked motor hyperactivity and aggressive behavior, and increased serum ACTH, corticosterone (CS) and brain prostaglandin-E2 production. Mortality was 100%. Immunization with strain R-15 prior to challenge with Syn17+ induced the production of neutralizing antibodies to HSV-1 Syn17+, and abolished the above clinical and neuroendocrine changes. Mortality was completely prevented. These results indicate that immunization with HSV-1 strain R-15 protects rats from lethal HSV-1 encephalitis and prevents its clinical and neurochemical manifestations.
    Full-text · Article · Aug 2004
    • Despite the fact that the majority of cells within the spheroids were PSA-NCAM + , the spheroids were clearly comprised of a mixed population of cells that expressed markers of both restricted and unrestricted progenitors. Several markers of tripotential progenitors, such as PSA-NCAM (Grinspan and Franceschini, 1995; Ben-Hur et al., 1998), Dlx2 (Marshall and Goldman, 2002), Olig2 (Marshall et al., 2005) and NG2 (Nishiyama et al., 1996; Aguirre et al., 2004) were expressed by a large percentage of the cells. Almost 35 % of the cells also expressed nestin, which is commonly associated with stem cells and early progenitors in the CNS (Dahlstrand et al., 1995; Kawaguchi et al., 2001; Beech et al., 2004; Mignone et al., 2004).
    [Show abstract] [Hide abstract] ABSTRACT: The subventricular zone (SVZ) contains neural stem cells and progenitors of various potentialities. Although initially parsed into A, B, and C cells, this germinal zone is comprised of a significantly more diverse population of cells. Here, we characterized a subset of postnatal PDGF-AA responsive precursors (PRPs) that express functional PDGFα and β receptors from birth to adulthood. When grown in PDGF-AA, dissociated neonatal rat SVZ cells divided to produce non-adherent clusters of progeny. Unlike the self-renewing EGF/FGF-2 responsive precursors that produce neurospheres, these PRPs failed to self-renew after 3 passages; therefore, we refer to the colonies they produce as spheroids. Upon differentiation these spheroids could produce neurons, type 1 astrocytes and oligodendrocytes. When maintained in medium supplemented with BMP-4 they also produced type 2 astrocytes. Using lineage tracing methods, it became evident that there were multiple types of PRPs, including a subset that could produce neurons, oligodendrocytes, type 1 and type 2 astrocytes; thus some of these PRPs represent a unique population of precursors that are quatropotential. Spheroids also could be generated from the newborn neocortex and they had the same potentiality as those from the SVZ. By contrast, the adult neocortex produced less than 20% of the numbers of spheroids than the adult SVZ and spheroids from the adult neocortex only differentiated into glial cells. Interestingly, SVZ spheroid producing capacity diminished only slightly from birth to adulthood. Altogether these data demonstrate that there are PRPs that persist in the SVZ that includes a unique population of quatropotential PDGF-AA responsive progenitors.
    Full-text · Article · Dec 2013
    • Total cellular RNA was isolated at 4, 7, 10, and 14 h post infection to obtain immediate-early (IE, in the presence of cycloheximide ), early (E, in the presence of cytosine arabinoside ), early-late (EL), and late (L) viral transcripts, respectively. RNA isolation was performed using the guanidinium/cesium chloride method as described previously (Rö Wolff et al., 1988 ). The reverse transcription step was carried out using the RNA LA PCR Kit Ver.
    [Show abstract] [Hide abstract] ABSTRACT: Tupaia herpesvirus (THV) was isolated from spontaneously degenerating tissue cultures of malignant lymphoma, lung, and spleen cell cultures of tree shrews (Tupaia spp.). In order to determine the phylogenetic relatedness of THV the complete nucleotide sequence of the viral terminase (VTER) gene locus (6223 bp) of Tupaia herpesvirus strain 2 (THV-2) was elucidated and analysed. The VTER gene locus, encoding one of the most highly conserved herpes viral proteins is composed of two exons. The intron contains five potential open reading frames (ORFs). The arrangement of these ORFs is colinear with the corresponding regions in the genomes of the mammalian cytomegaloviruses. The precise primary structure of the THV-2 VTER splice junction was determined using RT-PCR and was found to be in agreement with the corresponding splice donor and acceptor sites of the mammalian cytomegaloviruses. The comparison of all six putative THV-2 proteins with the corresponding counterparts in other herpesviruses revealed that THV resides between the Human and the Murine cytomegalovirus (HCMV, MCMV). These results are in agreement with our previous statement, that THV and the known cytomegaloviruses are closely related to each other and should be classified into one taxonomic group. The genetic data presented here and in previous studies are based on the detailed comparison of highly conserved viral genes. Consequently, the classification of the Human and the cytomegaloviruses into the two genera Cyto- and Muromegalovirus, that is mainly based on overall genome structure, should be reconsidered.
    Article · May 2001
    • These suggested to the authors that the core deficit was one of retrieval of lexical items from semantic input. Further supporting the idea that the thalamus may be involved in the use of semantic information to facilitate lexical retrieval, are the findings of category-specific naming deficits in patients with thalamic infarcts and deficits (Crosson, Moberg, Boone, Gonzalez Levin et al., 2005 ) and demonstrations that the thalamus may be involved in object recall (Segal, Williams, Kraut, & Hart, 2003; Slotnick, Moo, Kraut, Lesser, & Hart, 2002; Wahl et al., 2008). Analysis of the effects on language of thalamotomy or thalamic deep brain stimulation can avoid the limitations imparted by the idiosyncrasies of the thalamic vasculature, though the ability to make inferences about thalamic structure-function relationships via this approach is limited by the small range of thalamic targets employed (typically ventrolateral nucleus, pulvinar and intralaminar nuclei).
    [Show abstract] [Hide abstract] ABSTRACT: Herein, the literature regarding functional imaging of the thalamus during language tasks is reviewed. Fifty studies met criteria for analysis. Two of the most common task paradigms associated with thalamic activation were generative tasks (e.g. word or sentence generation) and naming, though activation was also seen in tasks that involve lexical decision, reading and working memory. Typically, thalamic activation was seen bilaterally, left greater than right, along with activation in frontal and temporal cortical regions. Thalamic activation was seen with perceptually challenging tasks, though few studies rigorously correlated thalamic activation with measures of attention or task difficulty. The peaks of activation loci were seen in virtually all thalamic regions, with a bias towards left-sided and midline activation. These analyses suggest that the thalamus may be involved in processes that involve manipulations of lexical information, but point to the need for more systematic study of the thalamus using language tasks.
    Full-text · Article · Sep 2012
    • Early studies with neural grafting of fetal tissues have demonstrated for the first time the potential of cell therapy in reversing behavioural defects in adulthood, induced during pregnancy [25]. Since then, the evolvement of stem cell therapy has shown a similar promise, using stem cells from different sources [26, 27]. Yet, while the capability of transplanted stem cells to correct postnatally induced neurobehavioral deficits has been extensively explored, the therapeutic potential of stem cells to repair the adult manifestations of prenatal neurodevelopmental disorders has been addressed to a much lesser extent.
    [Show abstract] [Hide abstract] ABSTRACT: Neurodevelopmental impairment can affect lifelong brain functions such as cognitive and social behaviour, and may contribute to aging-related changes of these functions. In the present study, we hypothesized that bone marrow-derived mesenchymal stem cells (MSC) administration may repair neurodevelopmental behavioural deficits by modulating adult hippocampal neurogenesis. Indeed, postnatal intracerebral transplantation of MSC has restored cognitive and social behaviour in mice prenatally exposed to valproic acid (VPA). MSC transplantation also restored post-developmental hippocampal neurogenesis, which was impaired in VPA-exposed mice displaying delayed differentiation and maturation of newly formed neurons in the granular cell layer of the dentate gyrus. Importantly, a statistically significant correlation was found between neuronal differentiation scores and behavioural scores, suggesting a mechanistic relation between the two. We thus conclude that post-developmental MSC administration can overcome prenatal neurodevelopmental deficits and restore cognitive and social behaviours via modulation of hippocampal adult neurogenesis.
    Full-text · Article · Feb 2017