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Intracerebral Infusion of Glial Cell Line-Derived Neurotrophic Factor Promotes Striatal Neurogenesis After Stroke in Adult Rats.

Kobayashi, Tohru LU ; Ahlenius, Henrik LU ; Thored, Pär LU ; Kobayashi, Rina LU ; Kokaia, Zaal LU and Lindvall, Olle LU (2006) In Stroke: a journal of cerebral circulation 37(9). p.2361-2367
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... (More)
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. (Less)
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author
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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
corpus striatum, stem cells, middle cerebral artery occlusion, cerebral ischemia, nerve growth factors
in
Stroke: a journal of cerebral circulation
volume
37
issue
9
pages
2361 - 2367
publisher
American Heart Association
external identifiers
  • pmid:16873711
  • wos:000241715900043
  • scopus:33748358157
ISSN
1524-4628
DOI
10.1161/01.STR.0000236025.44089.e1
language
English
LU publication?
yes
additional info
The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Stem Cell Center (013041110), Restorative Neurology (0131000160), Neurology, Lund (013027000)
id
f33a0dbf-8a70-428a-8134-f6694b807a7c (old id 158784)
alternative location
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=16873711&dopt=Abstract
date added to LUP
2016-04-01 15:57:04
date last changed
2020-09-02 02:34:10
@article{f33a0dbf-8a70-428a-8134-f6694b807a7c,
  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.},
  author       = {Kobayashi, Tohru and Ahlenius, Henrik and Thored, Pär and Kobayashi, Rina and Kokaia, Zaal and Lindvall, Olle},
  issn         = {1524-4628},
  language     = {eng},
  number       = {9},
  pages        = {2361--2367},
  publisher    = {American Heart Association},
  series       = {Stroke: a journal of cerebral circulation},
  title        = {Intracerebral Infusion of Glial Cell Line-Derived Neurotrophic Factor Promotes Striatal Neurogenesis After Stroke in Adult Rats.},
  url          = {http://dx.doi.org/10.1161/01.STR.0000236025.44089.e1},
  doi          = {10.1161/01.STR.0000236025.44089.e1},
  volume       = {37},
  year         = {2006},
}