title: PET imaging of serotoninergic neurotransmission with [(11)C]DASB and [(18)F]altanserin after focal cerebral ischemia in rats.
abstract: The use of selective serotonin reuptake inhibitors has shown functional improvement after stroke. Despite this, the role of serotoninergic neurotransmission after cerebral ischemia evolution and its involvement in functional recovery processes are still largely unknown. For this purpose, we performed in parallel in vivo magnetic resonance imaging and positron emission tomography (PET) with [(11)C]DASB and [(18)F]altanserin at 1, 3, 7, 14, 21, and 28 days after middle cerebral artery occlusion (MCAO) in rats. In the ischemic territory, PET with [(11)C]DASB and [(18)F]altanserin showed a dramatic decline in serotonin transporter (SERT) and 5-HT2A binding potential in the cortex and striatum after cerebral ischemia. Interestingly, a slight increase in [(11)C]DASB binding was observed from days 7 to 21 followed by the uppermost binding at day 28 in the ipsilateral midbrain. In contrast, no changes were observed in the contralateral hemisphere by using both radiotracers. Likewise, both functional and behavior testing showed major impaired outcome at day 1 after ischemia onset followed by a recovery of the sensorimotor function and dexterity from day 21 to day 28 after cerebral ischemia. Taken together, these results might evidence that SERT changes in the midbrain could have a key role in the functional recovery process after cerebral ischemia.
authors: Molecular Imaging Unit, CIC biomaGUNE, San Sebastian, Spain.
authors: Abraham
authors: A
authors: Martín
authors: Boguslaw
authors: B
authors: Szczupak
authors: Vanessa
authors: V
authors: Gómez-Vallejo
authors: Sandra
authors: S
authors: Plaza
authors: Daniel
authors: D
authors: Padró
authors: Ainhoa
authors: A
authors: Cano
authors: Jordi
authors: J
authors: Llop
mesh_terms: D000818:Animals; D001596:Benzylamines; D001921:Brain / Q000098:blood supply / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000473:pathology; D002545:Brain Ischemia / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000473:pathology; D002250:Carbon Radioisotopes; D003287:Contrast Media; D005462:Fluorine Radioisotopes; D020244:Infarction, Middle Cerebral Artery / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology; D007650:Ketanserin / Q000031:analogs & derivatives*; D049268:Positron-Emission Tomography / Q000379:methods*; D051381:Rats; D012701:Serotonin / Q000032:analysis / Q000378:metabolism*; D050486:Serotonin Plasma Membrane Transport Proteins / Q000032:analysis / Q000378:metabolism; D009435:Synaptic Transmission
chemical_list: D001596:Benzylamines; D002250:Carbon Radioisotopes; D003287:Contrast Media; D005462:Fluorine Radioisotopes; C420885:N,N-dimethyl-2-(2-amino-4-cyanophenylthio)benzylamine; D050486:Serotonin Plasma Membrane Transport Proteins; D012701:Serotonin; C071983:altanserin; D007650:Ketanserin
references: Nat Protoc. 2009;4(10):1560-4
references: 19798088
references: Neuroreport. 2001 May 25;12(7):1543-7
references: 11388445
references: Brain Res. 1998 Sep 14;805(1-2):241-54
references: 9733975
references: J Neurol. 2007 Jun;254(6):789-96
references: 17351723
references: Eur J Nucl Med. 1994 Sep;21(9):937-46
references: 7995287
references: Neurobiol Aging. 2012 Mar;33(3):479-87
references: 20510480
references: J Exp Biol. 1994 Nov;196:263-81
references: 7823027
references: Neurorehabil Neural Repair. 2008 May-Jun;22(3):311-4
references: 18219053
references: Biol Psychiatry. 2005 Jun 15;57(12):1510-6
references: 15953487
references: Neuroimage. 1996 Dec;4(3 Pt 1):153-8
references: 9345505
references: J Neurosci. 2010 Mar 3;30(9):3391-7
references: 20203198
references: Hum Brain Mapp. 2004 Jul;22(3):246-60
references: 15195291
references: Eur J Nucl Med. 2000 Nov;27(11):1719-22
references: 11105830
references: Eur J Nucl Med Mol Imaging. 2009 Feb;36(2):287-93
references: 18828013
references: J Neurosci Methods. 2013 Mar 15;213(2):179-87
references: 23291083
references: Neuroimage. 2010 Jan 1;49(1):121-6
references: 19660554
references: Neuropsychopharmacology. 2004 Dec;29(12):2235-41
references: 15367923
references: Neuroimage. 2010 Feb 1;49(3):2588-95
references: 19853044
references: Acta Neurol Scand. 2011 Apr;123(4):266-73
references: 20569228
references: Stroke. 2013 Mar;44(3):844-50
references: 23362083
references: J Cereb Blood Flow Metab. 2001 Sep;21(9):1097-104
references: 11524614
references: J Nucl Med. 1996 Dec;37(12):1976-81
references: 8970517
references: J Chem Neuroanat. 2010 Nov;40(3):232-8
references: 20600826
references: J Cereb Blood Flow Metab. 2002 Nov;22(11):1377-98
references: 12439295
references: Stroke. 2006 Jun;37(6):1525-32
references: 16675741
references: J Neurosci Res. 2009 Mar;87(4):1037-45
references: 18855941
references: Biol Psychiatry. 2006 Aug 1;60(3):207-17
references: 16875929
references: Neurobiol Dis. 2013 Mar;51:120-32
references: 23146994
references: Lancet Neurol. 2003 Aug;2(8):493-502
references: 12878437
references: Neurosurgery. 1992 Jul;31(1):100-6; discussion 106-7
references: 1641086
references: J Nucl Med. 1991 Dec;32(12):2266-72
references: 1744713
references: Stroke. 2003 Jun;34(6):1553-66
references: 12738893
references: Ann Neurol. 2008 May;63(5):549-60
references: 18481291
references: J Cereb Blood Flow Metab. 2013 Feb;33(2):244-52
references: 23149560
references: Lancet Neurol. 2011 Feb;10(2):123-30
references: 21216670
references: Stroke. 2010 Oct;41(10 Suppl):S114-6
references: 20876483
references: Stroke. 2009 Mar;40(3 Suppl):S136-8
references: 19064784
references: Trends Pharmacol Sci. 2007 Dec;28(12):629-36
references: 17996955
references: Stroke. 2011 Nov;42(11):3281-3
references: 21868736