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- Gustafsson, Elin, et al.
(författare)
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Intraventricular Infusion of TrkB-Fc Fusion Protein Promotes Ischemia-Induced Neurogenesis in Adult Rat Dentate Gyrus.
- 2003
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Ingår i: Stroke: a journal of cerebral circulation. - 1524-4628. ; 34:11, s. 2710-2715
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Tidskriftsartikel (refereegranskat)abstract
- Background and Purpose-We have previously shown that delivery of brain-derived neurotrophic factor (BDNF) through direct intrahippocampal gene transduction with a viral vector suppresses the formation of new dentate granule cells triggered by global forebrain ischemia. Here, we investigated whether inhibition of endogenous BDNF alters ischemia-induced neurogenesis in the dentate gyrus. Methods-Rats were subjected to 30 minutes of global forebrain ischemia and then received intraventricular infusion of either the BDNF scavenger, TrkB-Fc fusion protein, or control Hu-Fc for 2 weeks. In parallel, all animals were injected intraperitoneally with the mitosis marker 5-bromo-2'-deoxyuridine-5'-monophosphate (BrdU). Animals were killed at 2 or 6 weeks after the ischemic insult, and neurogenesis was then assessed immunocytochemically with epifluorescence or confocal microscopy. Results-Infusion of TrkB-Fc fusion protein gave rise to elevated numbers of ischemia-generated new neurons, double-labeled with BrdU and the early neuronal marker Hu or the mature neuronal marker NeuN, in the dentate subgranular zone and granule cell layer at 2 and 6 weeks after the insult. Conclusions-Our findings provide evidence that endogenous BDNF counteracts neuronal differentiation, but not cell proliferation or survival, in ischemia-induced dentate gyrus neurogenesis.
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- Kobayashi, Tohru, et al.
(författare)
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Intracerebral Infusion of Glial Cell Line-Derived Neurotrophic Factor Promotes Striatal Neurogenesis After Stroke in Adult Rats.
- 2006
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Ingår i: Stroke: a journal of cerebral circulation. - 1524-4628. ; 37:9, s. 2361-2367
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Tidskriftsartikel (refereegranskat)abstract
- Background and Purpose-Stroke triggers increased progenitor proliferation in the subventricular zone (SVZ) and the generation of medium spiny neurons in the damaged striatum of rodents. We explored whether intrastriatal infusion of glial cell line-derived neurotrophic factor (GDNF) promotes neurogenesis after stroke. Methods-Adult rats were subjected to 2-hour middle cerebral artery occlusion (MCAO). GDNF was infused into the ischemic striatum either during the first week after MCAO, with the animals being killed directly thereafter, or during the third and fourth weeks, with the rats being killed 1 week later. New cells were labeled with 5'-bromo-2'deoxyuridine (BrdU) on day 7 or during the second week, respectively. Neurogenesis was assessed immunocytochemically with antibodies against BrdU and neuronal, glial, or progenitor markers. GDNF receptor expression was analyzed in SVZ tissue and neurospheres by reverse transcription-polymerase chain reaction and immunocytochemistry. Results-GDNF infusion increased cell proliferation in the ipsilateral SVZ and the recruitment of new neuroblasts into the striatum after MCAO and improved survival of new mature neurons. The GDNF receptor GFR alpha 1 was upregulated in the SVZ 1 week after MCAO and was coexpressed with markers of dividing progenitor cells. Conclusions-Intrastriatal infusion of GDNF in the postischernic period promotes several steps of striatal neurogenesis after stroke., partly through direct action on SVZ progenitors. Because delivery of GDNF has biological effects in the human brain, our data suggest that administration of this factor may promote neurciregenerative responses in stroke patients.
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- Lindvall, Olle, et al.
(författare)
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Recovery and Rehabilitation in Stroke. Stem Cells.
- 2004
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Ingår i: Stroke: a journal of cerebral circulation. - 1524-4628. ; 35:11 suppl 1, s. 2691-2694
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Tidskriftsartikel (refereegranskat)abstract
- The recent demostration that neurons for transplantation can be generated from stem cells and that the adult brain produces new neurons in response to stroke has raised hope for the development of a stem cell therapy for patients affected with this disorder. In this review we propose a road map to the clinic and describe the different scientific tasks that need to be accomplished to move stem cell-based approaches toward application in stroke patients.
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- Lindvall, Olle, et al.
(författare)
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Stem cell research in stroke: how far from the clinic?
- 2011
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Ingår i: Stroke: a journal of cerebral circulation. - 1524-4628. ; 42:8, s. 2369-2375
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Tidskriftsartikel (refereegranskat)abstract
- Stem cell-based approaches hold much promise as potential novel treatments to restore function after stroke. Studies in animal models have shown that stem cell transplantation can improve function by replacing neurons or by trophic actions, modulation of inflammation, promotion of angiogenesis, remyelination and axonal plasticity, and neuroprotection. Endogenous neural stem cells are also potential therapeutic targets because they produce new neurons after stroke. Clinical trials are ongoing but there is currently no proven stem cell-based therapy for stroke. Preclinical studies and clinical research will be needed to optimize the therapeutic benefit and minimize the risks of stem cells in stroke.
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- Thored, Pär, et al.
(författare)
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Long-term neuroblast migration along blood vessels in an area with transient angiogenesis and increased vascularization after stroke
- 2007
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Ingår i: Stroke: a journal of cerebral circulation. - 1524-4628. ; 38:11, s. 3032-3039
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Tidskriftsartikel (refereegranskat)abstract
- Background and Purpose - Stroke induced by middle cerebral artery occlusion (MCAO) causes long-term formation of new striatal neurons from stem/progenitor cells in the subventricular zone (SVZ). We explored whether MCAO leads to hypoxia, changes in vessel density, and angiogenesis in the ipsilateral SVZ and adjacent striatum, and determined the relation between the migrating neuroblasts and the vasculature. Methods - Adult rats were subjected to 2 hours of MCAO. Hypoxia was studied by injecting Hypoxyprobe-1 during MCAO or 6 weeks later. Vessel density and length was estimated using stereology. New cells were labeled with 5'-bromo-2' deoxyuridine (BrdU) during weeks 1 and 2 or 7 and 8 after MCAO, and angiogenesis was assessed immunohistochemically with antibodies against BrdU and endothelial cell markers. Distance from neuroblasts to nearest vessel was measured using confocal microscopy. Results - The ischemic insult caused transient hypoxia and early, low-grade angiogenesis, but no damage or increase of vascular density in the SVZ. Angiogenesis was detected during the first 2 weeks in the dorsomedial striatum adjacent to the SVZ, which also showed long-lasting increase of vascularization. At 2, 6, and 16 weeks after MCAO, the majority of neuroblasts migrated through this area toward the damage, closely associated with blood vessels. Conclusions - The vasculature plays an important role for long-term striatal neurogenesis after stroke. During several months, neuroblasts migrate close to blood vessels through an area exhibiting early vascular remodeling and persistently increased vessel density. Optimizing vascularization should be an important strategy to promote neurogenesis and repair after stroke.
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