Neuropathological and behavioral consequences of adeno-associated viral vector-mediated continuous intrastriatal neurotrophin delivery in a focal ischemia model in rats.

Research output: Contribution to journalArticle

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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Authors
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Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Neurosciences

Keywords

  • Adenoviridae/*genetics, Animal, Brain Ischemia/pathology/*therapy, Cell Survival, Brain-Derived Neurotrophic Factor/*genetics, Corpus Striatum/pathology, Gene Therapy, Genetic Vectors, Infarction, Middle Cerebral Artery/pathology/therapy, Interneurons/cytology, Behavior, Male, Nerve Growth Factor/*genetics, Rats, Phenotype
Original languageEnglish
Pages (from-to)187-204
JournalNeurobiology of Disease
Volume9
Issue number2
Publication statusPublished - 2002
Publication categoryResearch
Peer-reviewedYes

Bibliographic note

The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Restorative Neurology (0131000160), Neurology, Lund (013027000)