PMID- 11895371 OWN - NLM STAT- MEDLINE DCOM- 20020509 LR - 20220223 IS - 0969-9961 (Print) IS - 0969-9961 (Linking) VI - 9 IP - 2 DP - 2002 Mar TI - Neuropathological and behavioral consequences of adeno-associated viral vector-mediated continuous intrastriatal neurotrophin delivery in a focal ischemia model in rats. PG - 187-204 AB - 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. CI - (c)2002 Elsevier Science (USA). FAU - Andsberg, Gunnar AU - Andsberg G AD - Section of Restorative Neurology, Wallenberg Neuroscience Center, University Hospital, Lund, Sweden. FAU - Kokaia, Zaal AU - Kokaia Z FAU - Klein, Ronald L AU - Klein RL FAU - Muzyczka, Nicholas AU - Muzyczka N FAU - Lindvall, Olle AU - Lindvall O FAU - Mandel, Ronald J AU - Mandel RJ LA - eng GR - P01 AG10485/AG/NIA NIH HHS/United States GR - P01 NS36302/NS/NINDS NIH HHS/United States PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - Neurobiol Dis JT - Neurobiology of disease JID - 9500169 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 9061-61-4 (Nerve Growth Factor) SB - IM MH - Adenoviridae/*genetics MH - Animals MH - Behavior, Animal MH - Brain Ischemia/pathology/*therapy MH - Brain-Derived Neurotrophic Factor/*genetics MH - Cell Survival MH - Corpus Striatum/pathology MH - Genetic Therapy MH - *Genetic Vectors MH - Infarction, Middle Cerebral Artery/pathology/therapy MH - Interneurons/cytology MH - Male MH - Nerve Growth Factor/*genetics MH - Phenotype MH - Rats MH - Rats, Wistar MH - Transgenes/genetics EDAT- 2002/03/16 10:00 MHDA- 2002/05/10 10:01 CRDT- 2002/03/16 10:00 PHST- 2002/03/16 10:00 [pubmed] PHST- 2002/05/10 10:01 [medline] PHST- 2002/03/16 10:00 [entrez] AID - S0969996101904565 [pii] AID - 10.1006/nbdi.2001.0456 [doi] PST - ppublish SO - Neurobiol Dis. 2002 Mar;9(2):187-204. doi: 10.1006/nbdi.2001.0456.