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Biomedical subjects

Tamir Ben-Hur

Publications and source records attributed to Tamir Ben-Hur.

At least 37 records · Page 2Linked to original sources
PubMed2005

Stent-assisted arterial reconstruction of traumatic extracranial carotid dissections.

OBJECTIVES: Dissection of the internal carotid artery is a well-recognized complication of craniocervical trauma with potentially grave neurological outcome in patients with significant ischemic symptoms. Traditional anticoagulation therapy may not be applicable, since anticoagulation is contraindicated in multiple trauma or penetrating injuries. In these circumstances, rapid stenting followed by antiplatelet therapy may be performed. METHODS: Patients with angiographically proven traumatic carotid artery dissection were prospectively selected for endovascular stenting according to clinical and radiological criteria. Essentially, patients with hemodynamic significant hemispheric hypoperfusion (as indicated by angiography or perfusion MRI), or in whom anticoagulant therapy failed clinically, or anticoagulation was contraindicated, were considered at high risk for stroke and were selected for stenting. Twelve patients were selected for stenting. RESULTS: In seven patients, multiple stents were implanted. Endovascular treatment reduced mean dissection stenosis from mean 65+/-33% (range, 10-100%) to mean 7+/-9% (range, 20-0%). In a mean clinical follow-up of 11.5+/-6.3 months (range 3-24 months), eight patients improved and four remained stable, and none of the patients had a TIA or stroke. Doppler U/S studies did not detect any signs of de novo in-stent stenosis in any of the patients at a mean follow-up time of 9.2+/-6.4 months. CONCLUSIONS: In selected cases of traumatic dissections of the carotid artery, endovascular stent-assisted angioplasty may immediately restore the integrity of the vessel lumen, even of acutely occluded arteries. This approach efficiently prevented the occurrence of new ischemic events, without additional anticoagulation.

Adolescent↗
PubMed2005

Protected stent-assisted carotid angioplasty in symptomatic high-risk NASCET-ineligible patients.

BACKGROUND AND OBJECTIVES: The North American Symptomatic Carotid Endarterectomy Trial (NASCET) excluded patients with severe medical, angiographic and neurological risk factors. The aim of this study is to determine the safety and efficacy of protected stent angioplasty in these high-risk patients. METHODS: Sixty-eight consecutive symptomatic NASCET-ineligible patients underwent protected stent-assisted carotid angioplasty. Patients were classified according to surgical risk based on Sundt criteria, and stratified for medical therapy according to stroke risk. Twenty-one patients were classified as Sundt grade 3 (30.8%) and 36 patients as grade 4 (52.9%). RESULTS: The procedure was technically successful in all patients, with stenosis averaging 82.1% (range 70-99%) before the procedure and 6.3% (range 0-30%) after treatment. There were no periprocedural deaths or major strokes, but two patients had minor, non-embolic stokes (2.9%). During a mean clinical follow-up of 14.4 months (range 1-30 months), no new neurological events occurred in relation to the treated vascular territory. CONCLUSIONS: Carotid angioplasty with cerebral protection can be performed safely in high-risk patients. During the follow-up period, angioplasty was highly effective in terms of stroke prevention and arterial patency.

Adult↗
PubMed2005

Stem cell therapy for myelin diseases.

Advances in cell biology have encouraged the hope that stem cell-based therapy can be used to heal central nervous system (CNS) diseases. Here, we will review the potential application of neural cell transplantation for the treatment of multiple sclerosis (MS) and other demyelinating disorders, mention some problematic issues that still face this therapeutic approach, and describe novel noninvasive methods for in vivo tracking of transplanted cells.

Animals↗
PubMed2004

Axonal damage in multiple sclerosis: a complex issue in a complex disease.

Multiple sclerosis is no longer considered to simply be an autoimmune demyelinating disease. Axonal destruction is another central pathological feature and a contributor to the accumulating disability of disease progression. The mechanism underlying axonal pathology has not been fully clarified but does not appear to be a simple one. The relationship between axonal damage and other components of the pathological features such as demyelination, inflammation and remyelination are under intense investigation. Experimental data suggest that therapeutic interventions such as the induction of rapid remyelination may lead to the protection of axons. In addition to immunomodulation, future strategies for neuroprotection may be of great importance.

Adjuvants, Immunologic↗
PubMed2004

Immunization with a nonpathogenic HSV-1 strain prevents clinical and neuroendocrine changes of experimental HSV-1 encephalitis.

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.

Adrenocorticotropic Hormone↗
PubMed2004

Susac syndrome.

OBJECTIVE: The objective of this study was to describe the clinical manifestations; radiographic, audiometric, and retinal fluorescein angiography findings; pathogenesis and treatment of Susac syndrome with review of the literature. STUDY DESIGN: We conducted a retrospective case review. SETTING: This study was conducted at a tertiary referral center. PATIENT: A 50-year-old woman presented with recurrent episodes of neurologic symptoms, bilateral sensorineural hearing loss, and silent retinal artery occlusion. INTERVENTIONS: The patient underwent complete evaluation, including magnetic resonance image studies, audiometric tests, and retinal fluorescein angiography. She was treated initially with corticosteroids and later with other immunosuppressive agents. RESULTS: The patient was initially diagnosed with left sudden sensorineural hearing loss. Despite comprehensive clinical and laboratory studies that did not reveal systemic disease, 3 weeks later, the patient developed vertigo, sensorineural hearing loss, and tinnitus in the opposite ear. The neurologic involvement and the bilateral audiologic manifestations raised the possibility of Susac syndrome. CONCLUSION: Susac syndrome is a rare disorder of unknown origin characterized by the triad of encephalopathy, fluctuating hearing loss, and visual loss resulting from microangiopathy of the brain, cochlea, and retina. The multiple organ involvement seen in Susac syndrome raises a differential diagnosis ranging from autoimmune disease, through systemic vasculitis, to multiple sclerosis. Otolaryngologists should be aware of this syndrome as a result of the vestibulocochlear manifestations and the multidisciplinary evaluation that is required.

Audiometry, Pure-Tone↗
PubMed2004

Transplantation of human embryonic stem cell-derived neural progenitors improves behavioral deficit in Parkinsonian rats.

Human embryonic stem cells (hESCs) may potentially serve as a renewable source of cells for transplantation. In Parkinson's disease, hESC-derived dopaminergic (DA) neurons may replace the degenerated neurons in the brain. Here, we generated highly enriched cultures of neural progenitors from hESCs and grafted the progenitors into the striatum of Parkinsonian rats. The grafts survived for at least 12 weeks, the transplanted cells stopped proliferating, and teratomas were not observed. The grafted cells differentiated in vivo into DA neurons, though at a low prevalence similar to that observed following spontaneous differentiation in vitro. Transplanted rats exhibited a significant partial correction of D-amphetamine and apomorphine-induced rotational behavior, along with a significant improvement in stepping and placing non-pharmacological behavioral tests. While transplantation of uncommitted hESC-derived neural progenitors induced partial behavioral recovery, our data indicate that the host-lesioned striatum could not direct the transplanted neural progenitors to acquire a dopaminergic fate. Hence, induction of their differentiation toward a midbrain fate prior to transplantation is probably required for complete correction of behavioral deficit. Our observations encourage further developments for the potential use of hESCs in the treatment of Parkinson's disease.

Animals↗
PubMed2003

Copper binding to PrPC may inhibit prion disease propagation.

Although it has been well established that PrP(C), the normal isoform of PrP(Sc), is a copper-binding protein, the role of this metal in the function of PrP(C) as well as in prion disease pathology remains unclear. Here, we show that when scrapie-infected neuroblastoma cells were cultured in the presence of copper, the accumulation of PrP(Sc) in these cells was markedly reduced. In addition, our results indicate that when normal neuroblastoma cells were cultured in the presence of copper ions, they could no longer bind and internalize PrP(Sc). In another set of experiments, copper was added to the drinking water of normal and scrapie-infected hamsters. Our results show that administration of copper to normal hamsters induced cerebellar PrP(C) accumulation. Most important, a significant delay in prion disease onset was observed when scrapie-infected hamsters were treated with copper. As shown before for neuroblastoma cells, also in vivo most of the copper-induced accumulation of PrP(C) was intracellular. We hypothesized that PrP(C) internalization by copper may hinder PrP(Sc) interaction with this molecule, and thereby affect prion disease propagation.

Animals↗
PubMed2003

Emergent stenting to treat patients with carotid artery dissection: clinically and radiologically directed therapeutic decision making.

BACKGROUND AND PURPOSE: Carotid artery dissection (CAD) is a common cause of stroke in young patients. Clots formed at the low-flow zone in the false arterial lumen may give rise to distal emboli, and the mural hematoma may eventually occlude the artery. Anticoagulation is currently the accepted treatment, but it is unknown which patients will improve spontaneously, which will respond to anticoagulation, and which will have an exacerbation of ischemic symptoms despite therapy. Endovascular treatment of CAD may be an attractive alternative to anticoagulation, and methods of identifying patients who stand to benefit from such therapy need to be established. METHODS: We present here 3 cases of spontaneous symptomatic CAD in which endovascular stenting procedures were performed on the basis of a paradigm aimed at identifying potentially salvageable but at-risk brain tissue by combining clinical with MRI (diffusion and perfusion) and angiographic data. RESULTS: Diffusion-perfusion MRI mismatches and/or evidence of cerebral ischemia on angiographic parenchymography were identified in all patients. They did not respond to anticoagulation, were therefore treated with endovascular stents, and had excellent outcomes. CONCLUSIONS: Endovascular stent placement may be an immediate, effective, and safe method of restoring vessel lumen integrity. It may be considered for selected patients who are clinically symptomatic despite anticoagulant treatment and in whom neuroimaging methods suggest that the neurological signs originate from a viable, hypoperfused, ischemic penumbra.

Angiography↗
PubMed2003

Transplanted multipotential neural precursor cells migrate into the inflamed white matter in response to experimental autoimmune encephalomyelitis.

Transplanted neural precursor cells remyelinate efficiently acutely demyelinated focal lesions. However, the clinical value of cell transplantation in a chronic, multifocal disease like multiple sclerosis will depend on the ability of transplanted cells to migrate to the multiple disease foci in the brain. Here, we expanded newborn rat neural precursor cells in spheres and transplanted them intracerebroventricularly or intrathecally in rats. The cells were labeled by the nuclear fluorescent dye Hoechst or by incubation with BrdU to enable their identification at 2 days and 2 weeks after transplantation, respectively. Spheres consisted of PSA-NCAM(+), nestin(+), NG2(-) undifferentiated precursor cells that differentiated in vitro into astrocytes, oligodendrocytes, and neurons. Spheres that were transplanted into intact rats remained mostly in the ventricles or in the spinal subarachnoid space. Following transplantation at peak of experimental autoimmune encephalomyelitis, cells migrated into the brain or spinal cord parenchyma, exclusively into inflamed white matter but not into adjacent gray matter regions. After 2 weeks, many transplanted cells had migrated into distant white matter tracts and acquired specific markers of the astroglial and oligodendroglial lineages. Thus, the inflammatory process may attract targeted migration of transplanted precursor cells into the brain parenchyma.

Acute Disease↗
PubMed2003

MR microscopy of magnetically labeled neurospheres transplanted into the Lewis EAE rat brain.

Stem cell transplantation is being explored as a new paradigm for the treatment of demyelinating diseases. Magnetically labeled multipotential neural precursor cells were transplanted into the ventricles of rats with acute experimental allergic encephalomyelitis (EAE) and high-resolution (microscopic) MR images were obtained ex vivo. Migration patterns of live cells into periventricular white matter structures could be easily visualized, with a good correlation of the corresponding histopathology. The present results confirm that MR cell tracking can be used to guide the development of successful transplantation protocols.

Animals↗
PubMed2003

Intraventricular transplantation of neural precursor cell spheres attenuates acute experimental allergic encephalomyelitis.

Brain transplantation of neural precursor cells (NPCs) has been proposed to enhance CNS regeneration. As the pathogenesis of most acute CNS diseases involves an inflammatory component, we studied whether NPC transplantation affects brain inflammation. Newborn rat multipotential NPCs were transplanted intraventriculary into acute experimental allergic encephalomyelitis (EAE) rats, a model for disseminated brain inflammation. Cells migrated into inflamed white matter and differentiated into glial cells. NPC transplantation attenuated the clinical severity of EAE and the brain inflammation, indicated by reduction in perivascular infiltrates and decreased expression of ICAM-1 and LFA-1. NPCs inhibited basal proliferation and proliferative responses to Concavalin-A and to MOG peptide of EAE rat-derived lymphocytes in vitro. Purified astrocytes inhibited lymphocyte proliferation in vitro, but did not migrate into EAE brains in vivo, and did not reduce EAE severity or brain inflammation. Thus, transplanted NPCs attenuate acute EAE via an anti-inflammatory mechanism which depends on cell ability to migrate into inflamed brain tissue.

Acute Disease↗
PubMed2003

Effects of proinflammatory cytokines on the growth, fate, and motility of multipotential neural precursor cells.

We have recently shown that the inflammatory process during experimental allergic encephalomyelitis (EAE), the animal model of MS, attracts transplanted NPC migration into the inflamed white matter. Here we studied how the proinflammatory cytokines tumor necrosis factor-alpha (TNFalpha) and interferon-gamma (IFNgamma) affect NPC growth, survival, differentiation, and migration. Newborn rat striatal NPCs were expanded in spheres as nestin+, PSA-NCAM+, NG2(-) cells, which differentiated into astrocytes, oligodendrocytes, and neurons. NPCs expressed receptors of TNFalpha and IFNgamma but not interleukin-1. TNFalpha and IFNgamma inhibited sphere cell proliferation, determined by [(3)H]thymidine and BrdU incorporation. IFNgamma increased apoptotic cell death (determined by TUNEL stains); this effect partially blocked by TNFalpha. Neither cytokine affected NPC lineage fate, determined by percentage of GFAP+, neurofilament+, and GalC+ cells after differentiation. TNFalpha and IFNgamma increased outward migration of cells from spheres in vitro. Thus, TNFalpha and IFNgamma, key players in MS and EAE, inhibit NPC proliferation and induce their migration.

Animals↗
PubMed2003

Stable genetic modification of human embryonic stem cells by lentiviral vectors.

Human embryonic stem (hES) cells are pluripotent cells derived from the inner cell mass of the early preimplantation embryo. An efficient strategy for stable genetic modification of hES cells may be highly valuable for manipulating the cells in vitro and may promote the study of hES cell biology, human embryogenesis, and the development of cell-based therapies. Here, we demonstrate that vectors derived from self-inactivating (SIN) human immunodeficiency virus type 1 (HIV-1) are efficient tools for stable genetic modification of hES cells. Transduction of hES cells by a modified vector derived from SIN HIV-1 and containing the woodchuck hepatitis regulatory element (WPRE) and the central polypurine tract (cPPT) sequence facilitated stable transgene expression during prolonged (38 weeks) undifferentiated proliferation in vitro. Southern blot analysis revealed that the viral vector had integrated into the host cells' DNA. Transgene expression was maintained throughout differentiation into progeny of all three germ layers both in vitro and in vivo in teratomas. Thus, the transduced hES cells retained the capability for self-renewal and their pluripotent potential. Genetic modification of hES cells by lentiviral vectors provides a powerful tool for basic and applied research in the area of human ES cells.

Animals↗
PubMed2003

Patterns of misdiagnosis of multiple sclerosis.

BACKGROUND: Multiple sclerosis is a chronic demyelinating disease of the central nervous system that presents with variable signs and symptoms. This variability in the clinical presentation may result in misdiagnosis, unnecessary referrals and misleading information to the patients. OBJECTIVES: To identify the types of misdiagnoses made on the presentation of MS. METHODS: Fifty consecutive MS patients were questioned on their early symptoms, their mental status, the disease course until the diagnosis was confirmed, and the different diagnoses they received. RESULTS: The patients had been referred to 2.2 +/- 1.3 specialists before seeing a neurologist, and learned about their disease 3.5 years after the onset of symptoms. Twenty-nine patients (58%) were initially given 41 wrong diagnoses. While the majority of women were misdiagnosed mentally, orthopedic work-up was offered to the men. Misdiagnosis of MS occurred most often in patients who presented with non-specific sensory symptoms that did not conform to a specific neurologic syndrome. The patients emphasized the fact that not knowing worsened their anxiety, whereas receiving the diagnosis enabled them to begin coping with their disease. CONCLUSIONS: MS is often overlooked when patients present with non-specific sensory complaints. The difference in type of misdiagnosis between men and women may reflect a gender-dependent bias in the way physicians interpret sensory complaints.

Adult↗
PubMed2002

Involvement of brain cytokines in the neurobehavioral disturbances induced by HIV-1 glycoprotein120.

Intracerebroventricular (i.c.v.) administration of HIV-1 glycoprotein 120 (gp120), the envelope protein used by the virus to gain access into immune cells, induces neurobehavioral alterations in rats. To examine the role of proinflammatory cytokines in mediating these effects, we measured the effects of gp120 on brain proinflammatory cytokine expression and the effects of anti-inflammatory agents, including interleukin-1 receptor antagonist (IL-1ra), pentoxifylline (a TNFalpha synthesis blocker) and IL-10, on gp120-induced sickness behavior. I.c.v. administration of gp120 induced the expression of IL-1beta, but not TNFalpha, mRNA in the hypothalamus, 3 h after the injection. Pretreatment of rats with IL-1ra, but not with pentoxifylline, significantly attenuated gp120-induced anorexia and loss in body weight, whereas both agents had no effect on gp120-induced reduction in locomotor activity in the open field. Pretreatment with either IL-1ra and pentoxifylline simultaneously, or with IL-10, produced effects that were similar to the effects of IL-1ra alone. Together, these findings indicate that IL-1, but not TNFalpha, mediates some of the behavioral effects of acute gp120 administration, suggesting that brain IL-1 may be involved in some of the neurobehavioral abnormalities evident in AIDS patients.

AIDS Dementia Complex↗