Growth Hormone Promotes Motor Function after Experimental Stroke and Enhances Recovery-Promoting Mechanisms within the Peri-Infarct Area

Article


Sanchez-Bezanilla, Sonia, Aberg, N. David, Crock, Patricia, Walker, Frederick R., Nilsson, Michael, Isgaard, Jörgen and Ong, Lin Kooi. 2020. "Growth Hormone Promotes Motor Function after Experimental Stroke and Enhances Recovery-Promoting Mechanisms within the Peri-Infarct Area." International Journal of Molecular Sciences. 21 (2), pp. 1-20. https://doi.org/10.3390/ijms21020606
Article Title

Growth Hormone Promotes Motor Function after Experimental Stroke and Enhances Recovery-Promoting Mechanisms within the Peri-Infarct Area

ERA Journal ID41930
Article CategoryArticle
AuthorsSanchez-Bezanilla, Sonia, Aberg, N. David, Crock, Patricia, Walker, Frederick R., Nilsson, Michael, Isgaard, Jörgen and Ong, Lin Kooi
Journal TitleInternational Journal of Molecular Sciences
Journal Citation21 (2), pp. 1-20
Article Number606
Number of Pages20
Year02 Jan 2020
PublisherMDPI AG
Place of PublicationSwitzerland
ISSN1422-0067
Digital Object Identifier (DOI)https://doi.org/10.3390/ijms21020606
Web Address (URL)https://www.mdpi.com/1422-0067/21/2/606
Abstract

Motor impairment is the most common and widely recognised clinical outcome after stroke. Current clinical practice in stroke rehabilitation focuses mainly on physical therapy, with no pharmacological intervention approved to facilitate functional recovery. Several studies have documented positive effects of growth hormone (GH) on cognitive function after stroke, but surprisingly, the effects on motor function remain unclear. In this study, photothrombotic occlusion targeting the motor and sensory cortex was induced in adult male mice. Two days post-stroke, mice were administered with recombinant human GH or saline, continuing for 28 days, followed by evaluation of motor function. Three days after initiation of the treatment, bromodeoxyuridine was administered for subsequent assessment of cell proliferation. Known neurorestorative processes within the peri-infarct area were evaluated by histological and biochemical analyses at 30 days post-stroke. This study demonstrated that GH treatment improves motor function after stroke by 50%-60%, as assessed using the cylinder and grid walk tests. Furthermore, the observed functional improvements occurred in parallel with a reduction in brain tissue loss, as well as increased cell proliferation, neurogenesis, increased synaptic plasticity and angiogenesis within the peri-infarct area. These findings provide new evidence about the potential therapeutic effects of GH in stroke recovery.

KeywordsIschemic stroke; growth hormone; motor recovery; neurogenesis; neuronal plasticity; vascular remodelling
ANZSRC Field of Research 2020320903. Central nervous system
310104. Cell neurochemistry
320208. Endocrinology
Byline AffiliationsUniversity of Newcastle
Hunter Medical Research Institute, Australia
University of Gothenburg, Sweden
Sahlgrenska University Hospital, Sweden
John Hunter Children’s Hospital, Australia
NHMRC Centre of Research Excellence Stroke Rehabilitation and Brain Recovery, Australia
Centre for Rehab Innovations, Australia
Nanyang Technological University, Singapore
Monash University
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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
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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