PMID- 23664961
OWN - NLM
STAT- MEDLINE
DCOM- 20131126
LR  - 20130812
IS  - 1090-2430 (Electronic)
IS  - 0014-4886 (Linking)
VI  - 247
DP  - 2013 Sep
TI  - Dopamine receptor activation increases glial cell line-derived neurotrophic 
      factor in experimental stroke.
PG  - 202-8
LID - S0014-4886(13)00147-7 [pii]
LID - 10.1016/j.expneurol.2013.04.016 [doi]
AB  - Treatment with levodopa enhances functional recovery after experimental stroke 
      but its mechanisms of action are elusive. Reactive astrocytes in the ischemic 
      hemisphere are involved in mechanisms promoting recovery and also express 
      dopamine 1 (D1) and dopamine 2 (D2) receptors. Here we investigated if the 
      activation of astrocytic dopamine receptors (D1 and D2) regulates the expression 
      of glial cell line-derived neurotrophic factor (GDNF) after combined in vitro 
      hypoxia/aglycemia (H/A) and studied the expression of GDNF in the ischemic brain 
      after treatment with levodopa/benserazide following transient occlusion of the 
      middle cerebral artery (tMCAO) in the rat. Twenty-four hours after H/A, GDNF 
      levels were upregulated in exposed astrocytes compared to normoxic control 
      cultures and further elevated by the addition of the selective D1 receptor 
      agonist (R)-(+)-SKF-38393 hydrochloride while D1 receptor antagonism by 
      R(+)-SCH-23390 hydrochloride significantly reduced GDNF. No effect on GDNF levels 
      was observed by the application of the D2 receptor agonist 
      R(-)-2,10,11-trihydroxy-N-propyl-noraporphine hydrobromide hydrate or 
      S-(-)-eticlopride hydrochloride (D2 receptor antagonist). After tMCAO, GDNF was 
      upregulated in D1 expressing reactive astrocytes in the peri-infarct area. In 
      addition, treatment with levodopa/benserazide significantly increased GDNF levels 
      in the infarct core and peri-infarct area after tMCAO without affecting the 
      expression of glial fibrillar acidic protein (GFAP), an intermediate filament and 
      marker of reactive gliosis. After stroke, GDNF levels increase in the ischemic 
      hemisphere in rats treated with levodopa, implicating GDNF in the mechanisms of 
      tissue reorganization and plasticity and in l-DOPA enhanced recovery of lost 
      brain function. Our results support levodopa treatment as a potential recovery 
      enhancing therapy in stroke patients.
CI  - Copyright (c) 2013 Elsevier Inc. All rights reserved.
FAU - Kuric, Enida
AU  - Kuric E
AD  - Department of Clinical Sciences, Division of Neurosurgery, Laboratory for 
      Experimental Brain Research, Lund University, BMC A13, S-22184 Lund, Sweden. 
      enida.kuric@med.lu.se
FAU - Wieloch, Tadeusz
AU  - Wieloch T
FAU - Ruscher, Karsten
AU  - Ruscher K
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20130509
PL  - United States
TA  - Exp Neurol
JT  - Experimental neurology
JID - 0370712
RN  - 0 (Dopamine Agents)
RN  - 0 (Glial Cell Line-Derived Neurotrophic Factor)
RN  - 0 (Glial Fibrillary Acidic Protein)
RN  - 0 (Nestin)
RN  - 0 (Receptors, Dopamine)
RN  - 46627O600J (Levodopa)
SB  - IM
MH  - Analysis of Variance
MH  - Animals
MH  - Astrocytes/drug effects/metabolism
MH  - Brain/drug effects/*metabolism
MH  - Brain Infarction/etiology/pathology/prevention & control
MH  - Cells, Cultured
MH  - Cerebral Cortex/cytology
MH  - Disease Models, Animal
MH  - Dopamine Agents/pharmacology
MH  - Gene Expression Regulation/drug effects
MH  - Glial Cell Line-Derived Neurotrophic Factor/*metabolism
MH  - Glial Fibrillary Acidic Protein/metabolism
MH  - Levodopa/pharmacology
MH  - Male
MH  - Nestin/metabolism
MH  - Rats
MH  - Rats, Wistar
MH  - Receptors, Dopamine/*metabolism
MH  - Stroke/complications/drug therapy/*pathology
OTO - NOTNLM
OT  - Astrocytes
OT  - Dopamine receptor
OT  - Glial cell line-derived neurotrophic factor
OT  - Glial fibrillary acidic protein
OT  - Levodopa
OT  - Stroke recovery
EDAT- 2013/05/15 06:00
MHDA- 2013/12/16 06:00
CRDT- 2013/05/14 06:00
PHST- 2013/02/15 00:00 [received]
PHST- 2013/04/26 00:00 [revised]
PHST- 2013/04/30 00:00 [accepted]
PHST- 2013/05/14 06:00 [entrez]
PHST- 2013/05/15 06:00 [pubmed]
PHST- 2013/12/16 06:00 [medline]
AID - S0014-4886(13)00147-7 [pii]
AID - 10.1016/j.expneurol.2013.04.016 [doi]
PST - ppublish
SO  - Exp Neurol. 2013 Sep;247:202-8. doi: 10.1016/j.expneurol.2013.04.016. Epub 2013 
      May 9.