| 1. |
- Lindholm, Paivi, et al.
(författare)
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MANF is widely expressed in mammalian tissues and differently regulated after ischemic and epileptic insults in rodent brain
- 2008
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Ingår i: Molecular and Cellular Neuroscience. - : Elsevier BV. - 1044-7431. ; 39:3, s. 356-371
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Tidskriftsartikel (refereegranskat)abstract
- The mesencephalic astrocyte-derived neurotrophic factor (MANF) has been described as a Survival factor for dopaminergic neurons in vitro, but its expression in mammalian tissues is poorly known. MANF and a homologous Protein, the conserved dopamine neurotrophic factor (CDNF), form a novel evolutionary conserved family of neurotrophic factors. Here we used in situ hybridization and immunohistochemistry to characterize MANF expression in developing and adult mouse. MANF expression was widespread in the nervous system and non-neuronal tissues. In the brain, relatively high MANF levels were detected in the cerebral cortex, hippocampus and cerebellar Purkinje cells. After status epilepticus, Manf mRNA expression was transiently increased in the dentate granule cell layer of hippocampus, thalamic reticular nucleus and in several cortical areas. In contrast, following global forebrain ischemia changes in Manf expression were widespread in the hippocampal formation and more restricted in cerebral cortex. The widespread expression of MANF together with its evolutionary conserved nature and regulation by brain insults suggest that it has important functions both under normal and pathological conditions in many tissue types. (C) 2008 Elsevier Inc. All rights reserved.
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| 2. |
- Lindvall, O, et al.
(författare)
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Cell therapy and transplantation in Parkinson's disease
- 2001
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Ingår i: Clinical Chemistry and Laboratory Medicine. - : De Gruyter. - 1434-6621 .- 1437-4331. ; 39:4, s. 356-361
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Tidskriftsartikel (refereegranskat)abstract
- Transplanted human fetal dopamine neurons can reinnervate the striatum in patients with Parkinson's disease (PD). Recent findings using positron emission tomography indicate that the grafts are functionally integrated and restore dopamine release in the patient's striatum. The grafts can exhibit long-term survival without immunological rejection and despite an ongoing disease process and continuous antiparkinsonian drug treatment. In the most successful cases, patients have been able to withdraw L-dopa treatment after transplantation and resume an independent life. About two-thirds of grafted patients have shown clinically useful, partial recovery of motor function. The major obstacle for the further development of this cell replacement strategy is that large amounts of human fetal mesencephalic tissue are needed for therapeutic effects. Stem cells hold promise as a virtually unlimited source of self-renewing progenitors for transplantation. The possibility to generate dopamine neurons from such cells is now being explored using different approaches. However, so far the generated neurons have survived poorly after transplantation in animals.
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| 3. |
- Ahlenius, Henrik, et al.
(författare)
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Adaptor Protein LNK Is a Negative Regulator of Brain Neural Stem Cell Proliferation after Stroke.
- 2012
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Ingår i: The Journal of Neuroscience : the official journal of the Society for Neuroscience. - 1529-2401. ; 32:15, s. 5151-5164
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Tidskriftsartikel (refereegranskat)abstract
- Ischemic stroke causes transient increase of neural stem and progenitor cell (NSPC) proliferation in the subventricular zone (SVZ), and migration of newly formed neuroblasts toward the damaged area where they mature to striatal neurons. The molecular mechanisms regulating this plastic response, probably involved in structural reorganization and functional recovery, are poorly understood. The adaptor protein LNK suppresses hematopoietic stem cell self-renewal, but its presence and role in the brain are poorly understood. Here we demonstrate that LNK is expressed in NSPCs in the adult mouse and human SVZ. Lnk(-/-) mice exhibited increased NSPC proliferation after stroke, but not in intact brain or following status epilepticus. Deletion of Lnk caused increased NSPC proliferation while overexpression decreased mitotic activity of these cells in vitro. We found that Lnk expression after stroke increased in SVZ through the transcription factors STAT1/3. LNK attenuated insulin-like growth factor 1 signaling by inhibition of AKT phosphorylation, resulting in reduced NSPC proliferation. Our findings identify LNK as a stroke-specific, endogenous negative regulator of NSPC proliferation, and suggest that LNK signaling is a novel mechanism influencing plastic responses in postischemic brain.
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| 4. |
- Ahlenius, Henrik, et al.
(författare)
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Neural stem and progenitor cells retain their potential for proliferation and differentiation into functional neurons despite lower number in aged brain.
- 2009
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Ingår i: The Journal of Neuroscience : the official journal of the Society for Neuroscience. - 1529-2401. ; 29:14, s. 4408-4419
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Tidskriftsartikel (refereegranskat)abstract
- Neurogenesis in the subventricular zone (SVZ), which gives rise to new neurons in the olfactory bulb, continues throughout life but declines with increasing age. Little is known about how aging affects the intrinsic properties of the neural stem and progenitor cells (NSCs) in SVZ and the functional characteristics of their neuronal progeny. Here, we have compared the properties of NSCs isolated from embryonic lateral ganglionic eminence and adult and aged SVZ in mice using in vivo and in vitro systems, analyzed their gene expression profile, and studied their electrophysiological characteristics before and after differentiation into neurons. We show a loss of NSCs in SVZ from aged mice accompanied by reduced expression of genes for NSC markers, developmentally important transcription factors, and neurogenic factors. However, when isolated in vitro, the NSCs from SVZ of aged animals have capacity for proliferation and multilineage differentiation, including production of functional neurons, similar to that of NSCs in adult mice, albeit with lower efficacy. These properties are of major importance when considering therapeutic applications of neuronal replacement from endogenous NSCs in the injured, aged brain.
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| 5. |
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| 6. |
- Ajmone-Cat, Maria Antonietta, et al.
(författare)
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Prostaglandin E(2) and BDNF levels in rat hippocampus are negatively correlated with status epilepticus severity: No impact on survival of seizure-generated neurons.
- 2006
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Ingår i: Neurobiology of Disease. - : Elsevier BV. - 0969-9961. ; 23:1, s. 23-35
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Tidskriftsartikel (refereegranskat)abstract
- Partial and generalized status epilepticus (pSE and gSE) trigger the same level of progenitor cell proliferation in adult dentate gyrus, but survival of new neurons is poor after gSE. Here, we show markedly elevated levels of prostaglandin E-2 (PGE(2)) and brain-derived neurotrophic factor (BDNF) in rat hippocampal formation at 7 days following pSE but not gSE. Administration of the cyclooxygenase (COX) inhibitor flurbiprofen for 1 week, starting at day 8 post-SE, abated PGE(2) and decreased BDNF levels, but did not affect survival of new neurons a weeks later. Thus, high PGE(2) and BDNF levels induced by pSE are probably not of major importance for survival of new neurons during the first days after formation. We propose that they modulate other aspects of synaptic and cellular plasticity, and thereby may influence epileptogenesis.
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| 7. |
- Aked, Joseph, et al.
(författare)
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Attitudes to Stem Cell Therapy among Ischemic Stroke Survivors in the Lund Stroke Recovery Study
- 2017
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Ingår i: Stem Cells and Development. - : Mary Ann Liebert Inc. - 1547-3287 .- 1557-8534. ; 26:8, s. 566-572
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Tidskriftsartikel (refereegranskat)abstract
- Preclinical studies suggest that stem cell therapy (SCT) may improve poststroke recovery, and clinical trials investigating safety are ongoing. However, knowledge about patients' attitudes to SCT in stroke is limited. We evaluated the knowledge and attitudes to this therapeutic approach as well as possible factors influencing this among stroke patients potentially suitable for SCT. Consecutive first-ever acute ischemic stroke patients aged 20-75 years with NIH stroke scale scores 1-18 were included. Exclusion criteria were severe comorbidities or infratentorial stroke. Clinical follow-up after 3-5 years assessed severity of residual stroke symptoms, cognitive function, functional status, patient-reported outcome, and comorbidity, and after receiving standardized information, the participants also completed an eight-item questionnaire on knowledge and attitudes about SCT. The relationships between clinical variables and positive attitude to SCT were assessed with logistic regression analyses. Of 108 patients included at baseline, 84 participated at follow-up and completed the questionnaire. In total, 12% had prior knowledge of SCT. When informed, 63% were positive toward it and 36% reported willingness to participate in SCT trials. Only 5%-8% expressed ethical considerations regarding different stem cell sources. Positive attitudes to SCT were associated with male gender (OR: 3.74; 95% CI: 1.45-9.61; P < 0.01) and better patient-reported outcome (OR: 1.02; 95% CI: 1.00-1.04; P < 0.05). In conclusion, stroke patients had limited prior knowledge of SCT, yet attitudes were positive among the majority after receiving standardized and neutral information. Gender and degree of stroke recovery may influence attitudes to SCT, indicating a need for targeted information to improve knowledge about SCT.
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| 8. |
- Andsberg, Gunnar, et al.
(författare)
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Neuropathological and behavioral consequences of adeno-associated viral vector-mediated continuous intrastriatal neurotrophin delivery in a focal ischemia model in rats.
- 2002
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Ingår i: Neurobiology of Disease. - : Elsevier BV. - 0969-9961. ; 9:2, s. 187-204
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Tidskriftsartikel (refereegranskat)abstract
- Nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) were continuously delivered to the striatum at biologically active levels via recombinant adeno-associated viral (rAAV) gene transfer 4-5 weeks prior to 30 min of middle cerebral artery occlusion (MCAO). The magnitude of the deficits in a battery of behavioral tests designed to assess striatal function was highly correlated to the extent of ischemic damage determined by unbiased stereological estimations of striatal neuron numbers. The delivery of neurotrophins lead to mild functional improvements in the ischemia-induced motor impairments assessed 3-5 weeks after the insult, in agreement with a small but significant increase of the survival of dorsolateral striatal neurons. Detailed phenotypic analysis demonstrated that the parvalbumin-containing interneurons were spared to a greater extent by the neurotrophin treatment as compared to the projection neurons, which agreed with the specificity for interneuron transduction by the rAAV vector. These data show the advantage of the never previously performed combination of precise quantification of the ischemia-induced neuropathology along with detailed behavioural analysis for assessing neuroprotection after stroke. We observe that intrastriatal delivery of NGF and BDNF using a viral vector system can mitigate, albeit only moderately, neuronal death following stroke, which leads to detectable functional sparing. (c)2002 Elsevier Science (USA).
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| 9. |
- Andsberg, Gunnar, et al.
(författare)
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Upregulation of p75 neurotrophin receptor after stroke in mice does not contribute to differential vulnerability of striatal neurons
- 2001
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Ingår i: Experimental Neurology. - : Elsevier BV. - 0014-4886. ; 169:2, s. 351-363
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Tidskriftsartikel (refereegranskat)abstract
- The survival of different neuron types and the expression of the p75 neurotrophin receptor (p75(NTR)) after focal cerebral ischemia were studied in the mouse striatum using immunocytochemical and histochemical techniques and stereological procedures. As assessed at 1 week after 30 min of middle cerebral artery occlusion, the order of vulnerability was projection neurons > parvalbumin-expressing interneurons > nitric oxide synthase-containing interneurons > cholinergic interneurons. Within the ischemic lesion, projection neurons were almost completely lost whereas cholinergic interneurons were spared. Calretinin-immunoreactive interneurons also seemed resistant to the insult. Expression of p75(NTR) was induced in cholinergic interneurons within the lesioned area, raising the possibility of a protective action. However, the number of cholinergic interneurons was unaffected in p75(NTR) knockout mice subjected to the same ischemic insult. These quantitative data demonstrate that striatal neurons in the mouse are differentially susceptible to ischemic damage and argue against a significant role of p75(NTR) for the high resistance of cholinergic interneurons.
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| 10. |
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