Effect of Serotonin and Levodopa in Ischemic Stroke

Summary

Cortical plasticity plays a pivotal role in functional recovery after a stroke. Neurotransmitter release, facilitates the creation of new synapses and promotes brain plasticity. In a pilot study, will evaluate the potential benefit of drugs that increase the release of neurotransmitters in patients with first stroke.

Timeline

Start

2015-01

Primary completion

2017-03

Completion

2019-10-31

Publications

• Background Thrift AG, Dewey HM, Macdonell RA, McNeil JJ, Donnan GA. Stroke incidence on the east coast of Australia: the North East Melbourne Stroke Incidence Study (NEMESIS). Stroke. 2000 Sep;31(9):2087-92. doi: 10.1161/01.str.31.9.2087.
• Background Bruel-Jungerman E, Rampon C, Laroche S. Adult hippocampal neurogenesis, synaptic plasticity and memory: facts and hypotheses. Rev Neurosci. 2007;18(2):93-114. doi: 10.1515/revneuro.2007.18.2.93.
• Background Jin K, Minami M, Lan JQ, Mao XO, Batteur S, Simon RP, Greenberg DA. Neurogenesis in dentate subgranular zone and rostral subventricular zone after focal cerebral ischemia in the rat. Proc Natl Acad Sci U S A. 2001 Apr 10;98(8):4710-5. doi: 10.1073/pnas.081011098.
• Background Arvidsson A, Collin T, Kirik D, Kokaia Z, Lindvall O. Neuronal replacement from endogenous precursors in the adult brain after stroke. Nat Med. 2002 Sep;8(9):963-70. doi: 10.1038/nm747. Epub 2002 Aug 5.
• Background Yamashita T, Ninomiya M, Hernandez Acosta P, Garcia-Verdugo JM, Sunabori T, Sakaguchi M, Adachi K, Kojima T, Hirota Y, Kawase T, Araki N, Abe K, Okano H, Sawamoto K. Subventricular zone-derived neuroblasts migrate and differentiate into mature neurons in the post-stroke adult striatum. J Neurosci. 2006 Jun 14;26(24):6627-36. doi: 10.1523/JNEUROSCI.0149-06.2006.
• Background Sun Y, Jin K, Xie L, Childs J, Mao XO, Logvinova A, Greenberg DA. VEGF-induced neuroprotection, neurogenesis, and angiogenesis after focal cerebral ischemia. J Clin Invest. 2003 Jun;111(12):1843-51. doi: 10.1172/JCI17977.
• Background Pariente J, Loubinoux I, Carel C, Albucher JF, Leger A, Manelfe C, Rascol O, Chollet F. Fluoxetine modulates motor performance and cerebral activation of patients recovering from stroke. Ann Neurol. 2001 Dec;50(6):718-29. doi: 10.1002/ana.1257.
• Background Lim CM, Kim SW, Park JY, Kim C, Yoon SH, Lee JK. Fluoxetine affords robust neuroprotection in the postischemic brain via its anti-inflammatory effect. J Neurosci Res. 2009 Mar;87(4):1037-45. doi: 10.1002/jnr.21899.
• Background Ruscher K, Kuric E, Wieloch T. Levodopa treatment improves functional recovery after experimental stroke. Stroke. 2012 Feb;43(2):507-13. doi: 10.1161/STROKEAHA.111.638767. Epub 2011 Nov 17.
• Background Gu Q. Neuromodulatory transmitter systems in the cortex and their role in cortical plasticity. Neuroscience. 2002;111(4):815-35. doi: 10.1016/s0306-4522(02)00026-x.
• Background Costa RM. Plastic corticostriatal circuits for action learning: what's dopamine got to do with it? Ann N Y Acad Sci. 2007 May;1104:172-91. doi: 10.1196/annals.1390.015. Epub 2007 Apr 13.
• Background Jacobs BL, Fornal CA. Serotonin and motor activity. Curr Opin Neurobiol. 1997 Dec;7(6):820-5. doi: 10.1016/s0959-4388(97)80141-9.
• Background Martinsson L, Hardemark H, Eksborg S. Amphetamines for improving recovery after stroke. Cochrane Database Syst Rev. 2007 Jan 24;2007(1):CD002090. doi: 10.1002/14651858.CD002090.pub2.
• Background Treig T, Werner C, Sachse M, Hesse S. No benefit from D-amphetamine when added to physiotherapy after stroke: a randomized, placebo-controlled study. Clin Rehabil. 2003 Sep;17(6):590-9. doi: 10.1191/0269215503cr653oa.
• Background Platz T, Kim IH, Engel U, Pinkowski C, Eickhof C, Kutzner M. Amphetamine fails to facilitate motor performance and to enhance motor recovery among stroke patients with mild arm paresis: interim analysis and termination of a double blind, randomised, placebo-controlled trial. Restor Neurol Neurosci. 2005;23(5-6):271-80.
• Background Gladstone DJ, Danells CJ, Armesto A, McIlroy WE, Staines WR, Graham SJ, Herrmann N, Szalai JP, Black SE; Subacute Therapy with Amphetamine and Rehabilitation for Stroke Study Investigators. Physiotherapy coupled with dextroamphetamine for rehabilitation after hemiparetic stroke: a randomized, double-blind, placebo-controlled trial. Stroke. 2006 Jan;37(1):179-85. doi: 10.1161/01.STR.0000195169.42447.78. Epub 2005 Dec 1.
• Background Chollet F, Tardy J, Albucher JF, Thalamas C, Berard E, Lamy C, Bejot Y, Deltour S, Jaillard A, Niclot P, Guillon B, Moulin T, Marque P, Pariente J, Arnaud C, Loubinoux I. Fluoxetine for motor recovery after acute ischaemic stroke (FLAME): a randomised placebo-controlled trial. Lancet Neurol. 2011 Feb;10(2):123-30. doi: 10.1016/S1474-4422(10)70314-8. Epub 2011 Jan 7.
• Background Petty GW, Brown RD Jr, Whisnant JP, Sicks JD, O'Fallon WM, Wiebers DO. Ischemic stroke subtypes : a population-based study of functional outcome, survival, and recurrence. Stroke. 2000 May;31(5):1062-8. doi: 10.1161/01.str.31.5.1062.
• Background Grade C, Redford B, Chrostowski J, Toussaint L, Blackwell B. Methylphenidate in early poststroke recovery: a double-blind, placebo-controlled study. Arch Phys Med Rehabil. 1998 Sep;79(9):1047-50. doi: 10.1016/s0003-9993(98)90169-1.
• Background Robinson RG, Schultz SK, Castillo C, Kopel T, Kosier JT, Newman RM, Curdue K, Petracca G, Starkstein SE. Nortriptyline versus fluoxetine in the treatment of depression and in short-term recovery after stroke: a placebo-controlled, double-blind study. Am J Psychiatry. 2000 Mar;157(3):351-9. doi: 10.1176/appi.ajp.157.3.351.
• Background Bilge C, Kocer E, Kocer A, Turk Boru U. Depression and functional outcome after stroke: the effect of antidepressant therapy on functional recovery. Eur J Phys Rehabil Med. 2008 Mar;44(1):13-8.
• Background Saxena SK, Ng TP, Koh G, Yong D, Fong NP. Is improvement in impaired cognition and depressive symptoms in post-stroke patients associated with recovery in activities of daily living? Acta Neurol Scand. 2007 May;115(5):339-46. doi: 10.1111/j.1600-0404.2006.00751.x.
• Background Sonde L, Lokk J. Effects of amphetamine and/or L-dopa and physiotherapy after stroke - a blinded randomized study. Acta Neurol Scand. 2007 Jan;115(1):55-9. doi: 10.1111/j.1600-0404.2006.00728.x.
• Background Dam M, Tonin P, De Boni A, Pizzolato G, Casson S, Ermani M, Freo U, Piron L, Battistin L. Effects of fluoxetine and maprotiline on functional recovery in poststroke hemiplegic patients undergoing rehabilitation therapy. Stroke. 1996 Jul;27(7):1211-4. doi: 10.1161/01.str.27.7.1211.
• Background Yan T, Hui-Chan CW, Li LS. Functional electrical stimulation improves motor recovery of the lower extremity and walking ability of subjects with first acute stroke: a randomized placebo-controlled trial. Stroke. 2005 Jan;36(1):80-5. doi: 10.1161/01.STR.0000149623.24906.63. Epub 2004 Nov 29.
• Background Cooke EV, Mares K, Clark A, Tallis RC, Pomeroy VM. The effects of increased dose of exercise-based therapies to enhance motor recovery after stroke: a systematic review and meta-analysis. BMC Med. 2010 Oct 13;8:60. doi: 10.1186/1741-7015-8-60.

Drugs

Indications