Growth Hormone Improves Cognitive Function After Experimental Stroke

Article


Ong, Lin Kooi, Chow, Wei Zhen, TeBay, Clifford, Kluge, Murielle, Pietrogrande, Giovanni, Zalewska, Katarzyna, Crock, Patricia, Åberg, N. David, Bivard, Andrew, Johnson, Sarah J., Walker, Frederick R., Nilsson, Michael and Isgaard, Jorgen. 2018. "Growth Hormone Improves Cognitive Function After Experimental Stroke." Stroke. 49 (5), pp. 1257 - 1266. https://doi.org/10.1161/STROKEAHA.117.020557
Article Title

Growth Hormone Improves Cognitive Function
After Experimental Stroke

ERA Journal ID16877
Article CategoryArticle
AuthorsOng, Lin Kooi, Chow, Wei Zhen, TeBay, Clifford, Kluge, Murielle, Pietrogrande, Giovanni, Zalewska, Katarzyna, Crock, Patricia, Åberg, N. David, Bivard, Andrew, Johnson, Sarah J., Walker, Frederick R., Nilsson, Michael and Isgaard, Jorgen
Journal TitleStroke
Journal Citation49 (5), pp. 1257 - 1266
Number of Pages10
YearMay 2018
Place of PublicationUnited States
ISSN0039-2499
1524-4628
Digital Object Identifier (DOI)https://doi.org/10.1161/STROKEAHA.117.020557
Web Address (URL)https://www.ahajournals.org/doi/10.1161/STROKEAHA.117.020557
Abstract

Background and Purpose-Cognitive impairment is a common outcome for stroke survivors. Growth hormone (GH) could represent a potential therapeutic option as this peptide hormone has been shown to improve cognition in various clinical conditions. In this study, we evaluated the effects of peripheral administration of GH at 48 hours poststroke for 28 days on cognitive function and the underlying mechanisms. Methods-Experimental stroke was induced by photothrombotic occlusion in young adult mice. We assessed the associative memory cognitive domain using mouse touchscreen platform for paired-associate learning task. We also evaluated neural tissue loss, neurotrophic factors, and markers of neuroplasticity and cerebrovascular remodeling using biochemical and histology analyses. Results-Our results show that GH-treated stroked mice made a significant improvement on the paired-associate learning task relative to non-GH-treated mice at the end of the study. Furthermore, we observed reduction of neural tissue loss in GH-treated stroked mice. We identified that GH treatment resulted in significantly higher levels of neurotrophic factors (IGF-1 [insulin-like growth factor-1] and VEGF [vascular endothelial growth factor]) in both the circulatory and periinfarct regions. GH treatment in stroked mice not only promoted protein levels and density of presynaptic marker (SYN-1 [synapsin-1]) and marker of myelination (MBP [myelin basic protein]) but also increased the density and area coverage of 2 major vasculature markers (CD31 and collagen-IV), within the peri-infarct region. Conclusions-These findings provide compelling preclinical evidence for the usage of GH as a potential therapeutic tool in the recovery phase of patients after stroke.

Keywordscognition; growth hormone; insulin-like growth factor-1; neuronal plasticity; stroke; vascular endothelial growth factor A; vascular remodeling
ANZSRC Field of Research 2020320903. Central nervous system
310104. Cell neurochemistry
320208. Endocrinology
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Byline AffiliationsUniversity of Newcastle
Hunter Medical Research Institute, Australia
NHMRC Centre of Research Excellence Stroke Rehabilitation and Brain Recovery, Australia
John Hunter Children’s Hospital, Australia
Sahlgrenska University Hospital, Sweden
University of Gothenburg, Sweden
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James, Morgan H., Quinn, Rikki K., Ong, Lin Kooi, Levi, Emily M., Smith, Doug W., Dickson, Phillip W. and Dayas, Christopher V.. 2016. "Rapamycin reduces motivated responding for cocaine and alters GluA1 expression in the ventral but not dorsal striatum." European Journal of Pharmacology. 784, pp. 147-154. https://doi.org/10.1016/j.ejphar.2016.05.013
Tyrosine hydroxylase regulation in adult rat striatum following short-term neonatal exposure to manganese
Peres, Tanara V., Ong, Lin K., Costa, Ana Paula, Eyng, Helena, Venske, De´bora K. R., Colle, Dirleise, Gonçalves, Filipe M., Lopes, Mark W., Farina, Marcelo, Aschner, Michael, Dickson, Phillip W., Dunkley, Peter R. and Leal, Rodrigo B.. 2016. "Tyrosine hydroxylase regulation in adult rat striatum following short-term neonatal exposure to manganese." Metallomics: integrated biometal science. 8 (6), pp. 597-604. https://doi.org/10.1039/c5mt00265f
Inflammation and dopamine synthesis in neurodegeneration
Ong, Lin Kooi, Briggs, G., Guan, L., Dunkley, P. and Dickson, P.. 2015. "Inflammation and dopamine synthesis in neurodegeneration." 25th Biennial Meeting of the International-Society-for-Neurochemistry Jointly with the 13th Meeting of the Asian-Pacific-Society-for-Neurochemistry in Conjunction with the 35th Meeting of the Australasian-Neuroscience-Society (2015). Cairns, Australia 23 - 27 Aug 2015 United Kingdom.
The role of inflammation and dopamine synthesis in Parkinson's disease
Ong, L. K., Briggs, G. D., Dunkley, P. R. and Dickson, P. W.. 2014. "The role of inflammation and dopamine synthesis in Parkinson's disease." 12th Biennial Meeting of the Asian-Pacific-Society-for-Neurochemistry (2014). Taiwan 23 - 26 Aug 2014 United Kingdom.
mTORC1 Inhibition in the Nucleus Accumbens ‘Protects’ Against the Expression of Drug Seeking and ‘Relapse’ and Is Associated with Reductions in GluA1 AMPAR and CAMKIIa Levels
James, Morgan H., Quinn, Rikki K., Ong, Lin Kooi, Levi, Emily M., Charnley, Janine L., Smith, Doug W., Dickson, Phillip W. and Dayas, Christopher V.. 2014. "mTORC1 Inhibition in the Nucleus Accumbens ‘Protects’ Against the Expression of Drug Seeking and ‘Relapse’ and Is Associated with Reductions in GluA1 AMPAR and CAMKIIa Levels." Neuropsychopharmacology. 39 (7), pp. 1694-1702. https://doi.org/10.1038/npp.2014.16
Neurobiological consequences of acute footshock stress: effects on tyrosine hydroxylase phosphorylation and activation in the rat brain and adrenal medulla
Ong, Lin Kooi, Guan, Liying, Damanhuri, Hanafi, Goodchild, Ann K., Bobrovskaya, Larisa, Dickson, Phillip W. and Dunkley, Peter R.. 2014. "Neurobiological consequences of acute footshock stress: effects on tyrosine hydroxylase phosphorylation and activation in the rat brain and adrenal medulla." Journal of Neurochemistry. 128 (4), pp. 547-560. https://doi.org/10.1111/jnc.12482
Early Life Stress and Post-Weaning High Fat Diet Alter Tyrosine Hydroxylase Regulation and AT1 Receptor Expression in the Adrenal Gland in a Sex Dependent Manner
Bobrovskaya, Larisa, Maniam, Jayanthi, Ong, Lin Kooi, Dunkley, Peter R. and Morris, Margaret J.. 2013. "Early Life Stress and Post-Weaning High Fat Diet Alter Tyrosine Hydroxylase Regulation and AT1 Receptor Expression in the Adrenal Gland in a Sex Dependent Manner." Neurochemical Research. 38 (4), pp. 826-833. https://doi.org/10.1007/s11064-013-0985-4
Functional Programming of the Autonomic Nervous System by Early Life Immune Exposure: Implications for Anxiety
Sominsky, Luba, Fuller, Erin A., Bondarenko, Evgeny, Ong, Lin Kooi, Averell, Lee, Nalivaiko, Eugene, Dunkley, Peter R., Dickson, Phillip W. and Hodgson, Deborah M.. 2013. "Functional Programming of the Autonomic Nervous System by Early Life Immune Exposure: Implications for Anxiety." PLoS One. 8 (3), pp. 1-13. https://doi.org/10.1371/journal.pone.0057700
Tyrosine Hydroxylase Phosphorylation in Catecholaminergic Brain Regions: A Marker of Activation following Acute Hypotension and Glucoprivation
Damanhuri, Hanafi A., Burke, Peter G. R., Ong, Lin K., Bobrovskaya, Larisa, Dickson, Phillip W., Dunkley, Peter R. and Goodchild, Ann K.. 2012. "Tyrosine Hydroxylase Phosphorylation in Catecholaminergic Brain Regions: A Marker of Activation following Acute Hypotension and Glucoprivation." PLoS One. 7 (11), pp. 1-19. https://doi.org/10.1371/journal.pone.0050535
The Sustained Phase of Tyrosine Hydroxylase Activation In vivo
Ong, Lin Kooi, Sominsky, Luba, Dickson, Phillip W., Hodgson, Deborah M. and Dunkley, Peter R.. 2012. "The Sustained Phase of Tyrosine Hydroxylase Activation In vivo." Neurochemical Research. 37 (9), pp. 1938-1943. https://doi.org/10.1007/s11064-012-0812-3
Increased microglial activation in the rat brain following neonatal exposure to a bacterial mimetic
Sominsky, L., Walker, A. K., Ong, L. K., Tynan, R. J., Walker, F. R. and Hodgson, D. M.. 2012. "Increased microglial activation in the rat brain following neonatal exposure to a bacterial mimetic." Behavioural Brain Research. 226 (1), pp. 351-356. https://doi.org/10.1016/j.bbr.2011.08.038
The effects of footshock and immobilization stress on tyrosine hydroxylase phosphorylation in the rat locus coeruleus and adrenal gland
Ong, L. K., Guan, L., Stutz, B., Dickson, P. W., Dunkley, P. R. and Bobrovskaya, L.. 2011. "The effects of footshock and immobilization stress on tyrosine hydroxylase phosphorylation in the rat locus coeruleus and adrenal gland." Neuroscience. 192, pp. 20-27. https://doi.org/10.1016/j.neuroscience.2011.06.087
Epigenetic Inheritance of Anxiety-Like Behaviour in Rats - Role of Early Life Exposure to a Bacterial Mimetic
Sominsky, L., Walker, A. K., Ong, L., Tynan, R. J., Walker, F. R. and Hodgson, D. M.. 2011. "Epigenetic Inheritance of Anxiety-Like Behaviour in Rats - Role of Early Life Exposure to a Bacterial Mimetic." Journal of Developmental Origins of Health and Disease. 2, pp. S109-S109.
Neonatal respiratory infection and adult re-infection: Effect on glucocorticoid and mineralocorticoid receptors in the hippocampus in BALB/c mice
Wynne, O., Horvat, J. C., Kim, R. Y., Ong, L. K., Smith, R., Hansbro, P. M., Clifton, V. L. and Hodgson, D. M.. 2011. "Neonatal respiratory infection and adult re-infection: Effect on glucocorticoid and mineralocorticoid receptors in the hippocampus in BALB/c mice." Brain, Behavior, and Immunity. 25 (6), pp. 1214-1222. https://doi.org/10.1016/j.bbi.2011.03.014
Sustained Phosphorylation of Tyrosine Hydroxylase at Serine 40 in VIVO
Ong, L. K., Sominsky, L., Walker, A. K., Hodgson, D. M., Goodchild, A. K., Bobrovskaya, L., Dickson, P. W. and Dunkley, P. R.. 2011. "Sustained Phosphorylation of Tyrosine Hydroxylase at Serine 40 in VIVO." 23rd Biennial Meeting of the International Society for Neurochemistry (2011). Athen, Greece 28 Aug - 01 Sep 2011 United Kingdom.
The Effect of Social Defeat on Tyrosine Hydroxylase Phosphorylation in the Rat Brain and Adrenal Gland
Ong, Lin Kooi, Bobrovskaya, Larisa, Walker, Frederick R., Day, Trevor A., Dickson, Phillip W. and Dunkley, Peter R.. 2011. "The Effect of Social Defeat on Tyrosine Hydroxylase Phosphorylation in the Rat Brain and Adrenal Gland." Neurochemical Research. 36 (1), pp. 27-33. https://doi.org/10.1007/s11064-010-0255-7
Tyrosine hydroxylase phosphorylation in response to footshock and restraint stress
Ong, L., Guan, L., Stutz, B., Dickson, P., Dunkley, P. and Bobrovskaya, L.. 2010. "Tyrosine hydroxylase phosphorylation in response to footshock and restraint stress." Journal of Neurochemistry. 115, pp. 77-77.
Signal transduction pathways and tyrosine hydroxylase regulation in the adrenal medulla following glucoprivation: An in vivo analysis
Bobrovskaya, Larisa, Damanhuri, Hanafi A., Ong, Lin Kooi, Schneider, Jennifer J., Dickson, Phillip W., Dunkley, Peter R. and Goodchild, Ann K.. 2010. "Signal transduction pathways and tyrosine hydroxylase regulation in the adrenal medulla following glucoprivation: An in vivo analysis." Neurochemistry International: the journal for the publication of cellular and molecular aspects of neurochemistry. 57 (2), pp. 162-167. https://doi.org/10.1016/j.neuint.2010.05.009
The effect of social conflict on tyrosine hydroxylase phosphorylation in catecholamine-producing cells from sprague-dawley rats
Ong, L., Bobrovskaya, L., Walker, F., Day, Trevor, Dickson, P. and Dunkley, P.. 2009. "The effect of social conflict on tyrosine hydroxylase phosphorylation in catecholamine-producing cells from sprague-dawley rats." 22nd Biennial Meeting of the International Society for Neurochemistry & Asian Pacific Society for Neurochemistry (2009). South Korea 23 - 29 Aug 2009 United Kingdom.
Cross-neutralisation of Australian brown and tiger snake venoms with commercial antivenoms: Cross-reactivity or antivenom mixtures?
O’Leary, Margaret A., Schneider, Jennifer J., Prakash Krishnan, Brian, Lavis, Christopher, McKendry, Amy, Ong, Lin Kooi and Isbister, Geoffrey K.. 2007. "Cross-neutralisation of Australian brown and tiger snake venoms with commercial antivenoms: Cross-reactivity or antivenom mixtures?" Toxicon. 50 (2), pp. 206-213. https://doi.org/10.1016/j.toxicon.2007.03.014