Anterograde delivery of brain-derived neurotrophic factor to striatum via nigral transduction of recombinant adeno-associated virus increases neuronal death but promotes neurogenic response following stroke.

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Gustafsson, Elin (author)

Anterograde delivery of brain-derived neurotrophic factor to striatum via nigral transduction of recombinant adeno-associated virus increases neuronal death but promotes neurogenic response following stroke.

Article/chapterEnglish2003

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2003-06-23
Wiley,2003
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LIBRIS-ID:oai:lup.lub.lu.se:d17f119d-5457-4a3a-a338-7fbbee42347e
https://lup.lub.lu.se/record/115713URI
https://doi.org/10.1046/j.1460-9568.2003.02713.xDOI

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Language:English
Summary in:English

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o explore the role of brain-derived neurotrophic factor for survival and generation of striatal neurons after stroke, recombinant adeno-associated viral vectors carrying brain-derived neurotrophic factor or green fluorescent protein genes were injected into right rat substantia nigra 4–5 weeks prior to 30 min ipsilateral of middle cerebral artery occlusion. The brain-derived neurotrophic factor–recombinant adeno-associated viral transduction markedly increased the production of brain-derived neurotrophic factor protein by nigral cells. Brain-derived neurotrophic factor was transported anterogradely to the striatum and released in biologically active form, as revealed by the hypertrophic response of striatal neuropeptide Y-positive interneurons. Animals transduced with brain-derived neurotrophic factor-recombinant adeno-associated virus also exhibited abnormalities in body posture and movements, including tilted body to the right, choreiform movements of left forelimb and head, and spontaneous, so-called 'barrel' rotation along their long axis. The continuous delivery of brain-derived neurotrophic factor had no effect on the survival of striatal projection neurons after stroke, but exaggerated the loss of cholinergic, and parvalbumin- and neuropeptide Y-positive, γ-aminobutyric acid-ergic interneurons. The high brain-derived neurotrophic factor levels in the animals subjected to stroke also gave rise to an increased number of striatal cells expressing doublecortin, a marker for migrating neuroblasts, and cells double-labelled with the mitotic marker, 5-bromo-2'-deoxyuridine-5'monophosphate, and early neuronal (Hu) or striatal neuronal (Meis2) markers. Our findings indicate that long-term anterograde delivery of high levels of brain-derived neurotrophic factor increases the vulnerability of striatal interneurons to stroke-induced damage. Concomitantly, brain-derived neurotrophic factor potentiates the stroke-induced neurogenic response, at least at early stages.

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Andsberg, GunnarLund University,Lunds universitet,Wallenberg Neurocentrum, Lund,Medicinska fakulteten,Wallenberg Neuroscience Centre, Lund,Faculty of Medicine(Swepub:lu)neur-gan (author)
Darsalia, VladimerLund University,Lunds universitet,Wallenberg Neurocentrum, Lund,Medicinska fakulteten,Wallenberg Neuroscience Centre, Lund,Faculty of Medicine(Swepub:lu)neur-vda (author)
Mohapel, PaulLund University,Lunds universitet,Wallenberg Neurocentrum, Lund,Medicinska fakulteten,Wallenberg Neuroscience Centre, Lund,Faculty of Medicine(Swepub:lu)neur-pmo (author)
Mandel, Ronald J. (author)
Kirik, DenizLund University,Lunds universitet,Neurobiologi,Forskargrupper vid Lunds universitet,Neurobiology,Lund University Research Groups(Swepub:lu)mphy-dki (author)
Lindvall, OlleLund University,Lunds universitet,Wallenberg Neurocentrum, Lund,Medicinska fakulteten,Wallenberg Neuroscience Centre, Lund,Faculty of Medicine(Swepub:lu)neur-oli (author)
Kokaia, ZaalLund University,Lunds universitet,Wallenberg Neurocentrum, Lund,Medicinska fakulteten,Wallenberg Neuroscience Centre, Lund,Faculty of Medicine(Swepub:lu)neur-zko (author)
Wallenberg Neurocentrum, LundMedicinska fakulteten (creator_code:org_t)

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In:European Journal of Neuroscience: Wiley17:12, s. 2667-26781460-95680953-816X

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By the author/editor: Gustafsson, Elin; Andsberg, Gunnar; Darsalia, Vladim ...; Mohapel, Paul; Mandel, Ronald J ...; Kirik, Deniz; show more...; Lindvall, Olle; Kokaia, Zaal; show less...

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MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Basic Medicine; and Neurosciences

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