Dr Andrew Clarkson, Our People, Brain Health Research Centre, University of Otago, New Zealand

Andrew Clarkson Dr Clarkson’s work focuses on promoting neuroprotection, regeneration and repair mechanisms to improve recovery of function following a stroke.

Even though acute stroke deaths have declined in recent years, as the population ages, the incidence of stroke is increasing resulting in a larger population of disabled stroke patients. The ability of the adult brain to regenerate or recover from acute injury is limited and stroke is now one of the leading causes of long-term disability.

The mechanisms of recovery after stroke have not been well defined. Recent studies show a limited capacity for neural repair after stroke, including re-mapping of cognitive functions and sprouting new connections in tissue adjacent to the stroke. Neurorehabilitation from using repetitive and patterned use of affected limbs linked to the affected brain regions has been shown to promote partial recovery via activity-based re-programming. An understanding of these neural repair mechanisms within the peri-infarct cortex may lead to therapies that promote recovery. Neurorehabiliation uses similar cognitive rules to learning and memory and Dr Clarkson postulates that cellular mechanisms of learning and memory are involved in the underlying processes of recovery following a focal brain injury.

The overall goal of his research program is to identify mechanisms of neural repair after stroke by modulating cortical excitability. Dr Clarkson’s recent studies indicate that just like learning and memory processes, cortical excitability can influence neural repair after stroke. Using novel functional and cortical motor mapping techniques, he will systematically assess the molecular mechanisms associated with learning and memory and how they may support or regulate neural repair and plasticity following focal brain injury. Intensive rehabilitation, drug therapy and, more recently, stem cells are combined to enhance brain repair processes. Post-stroke recovery is assessed through optical imaging and behavioural, electrophysiological, and anatomical measures. His research may produce novel pharmacological tools to help improve neurorehabilitation and recovery.

Read more about Dr Clarkson’s research

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Publications

Barzegar-Fallah, A., Houlton, J., Barwick, D., Shavandi, A., Ali, M. A., Clarkson, A. N., & Alimoradi, H. (2021). From barriers to bridges: Glycans in naonparenteral nanomedicines. In P. Kesharwani, S. Taurin & K. Greish (Eds.), Theory and applications of nonparenteral nanomedicines. (pp. 467-487). London, UK: Elsevier. doi: 10.1016/B978-0-12-820466-5.00019-3

van Nieuwenhuijzen, P. S., Parker, K., Liao, V., Houlton, J., Kim, H.-Y., Johnston, G. A. R., … Clarkson, A. N. (2021). Targeting GABA_C receptors improves post‐stroke motor recovery. Brain Sciences, 11(3), 315. doi: 10.3390/brainsci11030315

Boni, R., Ali, A., Giteru, S. G., Shavandi, A., & Clarkson, A. N. (2020). Silk fibroin nanoscaffolds for neural tissue engineering. Journal of Materials Science: Materials in Medicine, 31, 81. doi: 10.1007/s10856-020-06422-5

Atienza-Roca, P., Kieser, D., Cui, X., Bathish, B., Ramaswamy, Y., Hooper, G. J., Clarkson, A. N., … Wise, L. M., Woodfield, T. B. F., & Lim, K. S. (2020). Visible light mediated PVA-tyramine hydrogels for covalent incorporation and tailorable release of functional growth factors. Biomaterials Science, 8(18), 5005-5019. doi: 10.1039/D0BM00603C

Houlton, J., Barwick, D., & Clarkson, A. N. (2020). Frontal cortex stroke-induced impairment in spatial working memory on the trial-unique nonmatching-to-location task in mice. Neurobiology of Learning & Memory. Advance online publication. doi: 10.1016/j.nlm.2020.107355

Chapter in Book - Research
Journal - Research Article

Chapter in Book - Research

Lie, M. E. K., Al-Khawaja, A., Damgaard, M., Haugaard, A. S., Schousboe, A., Clarkson, A. N., & Wellendorph, P. (2017). Glial GABA transporters as modulators of inhibitory signalling in epilepsy and stroke. In A. Ortega & A. Schousboe (Eds.), Glial amino acid transporters. (pp. 137-167). Cham, Switzerland: Springer. doi: 10.1007/978-3-319-55769-4_7

Clarkson, A. N., & Chebib, M. (2014). The role of peri-synaptic GABA receptors after stroke. In A. C. Errington, V. Crunelli & G. Di Giovanni (Eds.), Extrasynaptic GABA_A receptors: The receptors (Vol. 27). (pp. 179-205). New York: Springer. doi: 10.1007/978-1-4939-1426-5_9

Clarkson, A. N. (2009). Secondary cardiovascular abnormalities subsequent to cerebral hypoxia-ischaemia. In E. H. Bennington (Ed.), Horizons in world cardiovascular research (Vol. 1). New York: Nova Science.

Clarkson, A. N. (2008). Secondary cardiovascular abnormalities subsequent to cerebral hypoxia-ischaemia. In O. M. Roux (Ed.), Brain hypoxia-ischemia research progress. (pp. 19-56). New York: Nova Science.

Clarkson, A. N., & Appleton, I. (2007). Cerebral hypoxia-ischemia-induced neuronal and cardiac impairment. In C. Kaur (Ed.), Hypoxia and the central nervous system. (pp. 109-144). Trivandrum, India: Transworld Research Network.

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Journal - Research Article

McFall, A., Hietamies, T. M., Bernard, A., Aimable, M., Allan, S. M., Bath, P. M., … Clarkson, A. N., … Quinn, T. J. (2020). UK consensus on pre-clinical vascular cognitive impairment functional outcomes assessment: Questionnaire and workshop proceedings. Journal of Cerebral Blood Flow & Metabolism, 47(7), 1402-1414. doi: 10.1177/0271678X20910552

Soo, J. Y., Wiese, M. D., Dyson, R. M., Gray, C. L., Clarkson, A. N., Morrison, J. L., & Berry, M. J. (2020). Methamphetamine administration increases hepatic CYP1A2 but not CYP3A activity in female guinea pigs. PLoS ONE, 15(5), e0233010. doi: 10.1371/journal.pone.0233010

Cirillo, J., Mooney, R. A., Ackerley, S. J., Barber, P. A., Borges, V. M., Clarkson, A. N., … Byblow, W. D. (2020). Neurochemical balance and inhibition at the subacute stage after stroke. Journal of Neurophysiology, 123, 1775-1790. doi: 10.1152/jn.00561.2019

Neumann, S., Boothman-Burrell, L., Gowing, E. K., Jacobsen, T. A., Ahring, P. K., Young, S. L., … Clarkson, A. N. (2019). The delta-subunit selective GABA_A receptor modulator, DS2, improves stroke recovery via an anti-inflammatory mechanism. Frontiers in Neuroscience, 13, 1133. doi: 10.3389/fnins.2019.01133

Clarkson, A. N., Boothman-Burrell, L., Dósa, Z., Nagaraja, R. Y., Jin, L., Parker, K., … Neumann, S., Gowing, E. K., … Chebib, M. (2019). The flavonoid, 2'-methoxy-6-methylflavone, affords neuroprotection following focal cerebral ischaemia. Journal of Cerebral Blood Flow & Metabolism, 39(7), 1266-1282. doi: 10.1177/0271678x18755628

Lie, M. E. K., Gowing, E. K., Johansen, N. B., Dalby, N. O., Thiesen, L., Wellendorph, P., & Clarkson, A. N. (2019). GAT3 selective substrate L-isoserine upregulates GAT3 expression and increases functional recovery after a focal ischemic stroke in mice. Journal of Cerebral Blood Flow & Metabolism, 39(1), 74-88. doi: 10.1177/0271678x17744123

Hillman, K. L., Wall, H. J., Matthews, L. O., Gowing, E. K., & Clarkson, A. N. (2019). Altered hippocampal-prefrontal dynamics following medial prefrontal stroke in mouse. NeuroMolecular Medicine, 21, 401-413. doi: 10.1007/s12017-019-08557-3

Houlton, J., Zhou, L. Y. Y., Barwick, D., Gowing, E. K., & Clarkson, A. N. (2019). Stroke induces a BDNF-dependent improvement in cognitive flexibility in aged mice. Neural Plasticity, 2019, 1460890. doi: 10.1155/2019/1460890

Houlton, J., Abumaria, N., Hinkley, S. F. R., & Clarkson, A. N. (2019). Therapeutic potential of neurotrophins for repair after brain injury: A helping hand from biomaterials. Frontiers in Neuroscience, 13, 790. doi: 10.3389/fnins.2019.00790

Kluge, M. G., Jones, K., Ong, L. K., Gowing, E. K., Nilsson, M., Clarkson, A. N., & Walker, F. R. (2018). Age-dependent disturbances of neuronal and glial protein expression profiles in areas of secondary neurodegeneration post-stroke. Neuroscience, 393, 185-195. doi: 10.1016/j.neuroscience.2018.07.034

Johnston, M., Clarkson, A. N., Gowing, E. K., Scarf, D., & Colombo, M. (2018). The effects of nidopallium caudolaterale inactivation on serial-order behaviour in pigeons (Columba livia). Journal of Neurophysiology, 120(3), 1143-1152. doi: 10.1152/jn.00167.2018

Evans, M. A., Lim, R., Kim, H. A., Chu, H. X., Gardiner-Mann, C. V., Taylor, K. W. E., … Neumann, S., … Gowing, E. K., … Clarkson, A. N., … Broughton, B. R. S. (2018). Acute or delayed systemic administration of human amnion epithelial cells improves outcomes in experimental stroke. Stroke, 49(3), 700-709. doi: 10.1161/strokeaha.117.019136

Lie, M. E. K., Gowing, E. K., Clausen, R. P., Wellendorph, P., & Clarkson, A. N. (2018). Inhibition of GABA transporters fails to afford significant protection following focal cerebral ischemia. Journal of Cerebral Blood Flow & Metabolism, 38(1), 166-173. doi: 10.1177/0271678x17743669

Allan, P. D., Tzeng, Y.-C., Gowing, E. K., Clarkson, A. N., & Fan, J.-L. (2018). Dietary nitrate supplementation reduces low frequency blood pressure fluctuations in rats following distal middle cerebral artery occlusion. Journal of Applied Physiology, 125(3), 862-869. doi: 10.1152/japplphysiol.01081.2017

Evans, M. A., Ah Kim, H., Hann Ling, Y., Uong, S., Vinh, A., De Silva, T. M., … Clarkson, A. N., … Sobey, C. G. (2018). Vitamin D₃ supplementation reduces subsequent brain injury and inflammation associated with ischemic stroke. NeuroMolecular Medicine, 20(1), 147-159. doi: 10.1007/s12017-018-8484-z

Evans, M. A., Kim, H. A., De Silva, T. M., Arumugam, T. V., Clarkson, A. N., Drummond, G. R., … Sobey, C. G. (2018). Diet-induced vitamin D deficiency has no effect on acute post-stroke outcomes in young male mice. Journal of Cerebral Blood Flow & Metabolism, 38(11), 1968-1978. doi: 10.1177/0271678x17719208

Parker, K., Berretta, A., Saenger, S., Sivaramakrishnan, M., Shirley, S. A., Metzger, F., & Clarkson, A. N. (2017). PEGylated insulin-like growth factor-I affords protection and facilitates recovery of lost functions post-focal ischemia. Scientific Reports, 7(1), 241. doi: 10.1038/s41598-017-00336-z

Smith, G. P. S., McLaughlin, A., Clarkson, A. N., Gordon, K. C., & Walker, G. F. (2017). Raman microscopic imaging of electrospun fibers made from a polycaprolactone and polyethylene oxide blend. Vibrational Spectroscopy, 92, 27-34. doi: 10.1016/j.vibspec.2017.05.002

Yarragudi, S. B., Richter, R., Lee, H., Walker, G. F., Clarkson, A. N., Kumar, H., & Rizwan, S. B. (2017). Formulation of olfactory-targeted microparticles with tamarind seed polysaccharide to improve nose-to-brain transport of drugs. Carbohydrate Polymers, 163, 216-226. doi: 10.1016/j.carbpol.2017.01.044

Younus, M., Prentice, R. N., Clarkson, A. N., Boyd, B. J., & Rizwan, S. B. (2016). Incorporation of an endogenous neuromodulatory lipid, oleoylethanolamide, into cubosomes: Nanostructural characterization. Langmuir, 32(35), 8942-8950. doi: 10.1021/acs.langmuir.6b02395

Berretta, A., Gowing, E. K., Jasoni, C. L., & Clarkson, A. N. (2016). Sonic hedgehog stimulates neurite outgrowth in a mechanical stretch model of reactive-astrogliosis. Scientific Reports, 6, 21896. doi: 10.1038/srep21896

Che Has, A. T., Absalom, N., van Nieuwenhuijzen, P. S., Clarkson, A. N., Ahring, P. K., & Chebib, M. (2016). Zolpidem is a potent stoichiometry-selective modulator of α1β3 GABA_A receptors: Evidence of a novel benzodiazepine site in the α1-α1 interface. Scientific Reports, 6, 28674. doi: 10.1038/srep28674

Zhou, L. Y. Y., Wright, T. E., & Clarkson, A. N. (2016). Prefrontal cortex stroke induces delayed impairment in spatial memory. Behavioural Brain Research, 296, 373-378. doi: 10.1016/j.bbr.2015.08.022

Neumann, S., Shields, N. J., Balle, T., Chebib, M., & Clarkson, A. N. (2015). Innate immunity and inflammation post-stroke: An α7-nicotinic agonist perspective. International Journal of Molecular Sciences, 16(12), 29029-29046. doi: 10.3390/ijms161226141

Clarkson, A. N., Parker, K., Nilsson, M., Walker, F. R., & Gowing, E. K. (2015). Combined ampakine and BDNF treatments enhance poststroke functional recovery in aged mice via AKT-CREB signaling. Journal of Cerebral Blood Flow & Metabolism, 35, 1272-1279. doi: 10.1038/jcbfm.2015.33

Van Slooten, A. R., Sun, Y., Clarkson, A. N., & Connor, B. J. (2015). L-NIO as a novel mechanism for inducing focal cerebral ischemia in the adult rat brain. Journal of Neuroscience Methods, 245, 44-57. doi: 10.1016/j.jneumeth.2015.02.022

Patience, M. J., Zouikr, I., Jones, K., Clarkson, A. N., Isgaard, J., Johnson, S. J., … Nilsson, M. (2015). Photothrombotic stroke induces persistent ipsilateral and contralateral astrogliosis in key cognitive control nuclei. Neurochemical Research, 40(2), 362-371. doi: 10.1007/s11064-014-1487-8

Jones, K. A., Zouikr, I., Patience, M., Clarkson, A. N., Isgaard, J., Johnson, S. J., … Walker, F. R. (2015). Chronic stress exacerbates neuronal loss associated with secondary neurodegeneration and suppresses microglial-like cells following focal motor cortex ischemia in the mouse. Brain, Behavior, & Immunity, 48, 57-67. doi: 10.1016/j.bbi.2015.02.014

López-Valdés, H. E., Clarkson, A. N., Ao, Y., Charles, A. C., Carmichael, S. T., Sofroniew, M. V., & Brennan, K. C. (2014). Memantine enhances recovery from stroke. Stroke, 45, 2093-2100. doi: 10.1161/strokeaha.113.004476

Bix, G. J., Gowing, E. K., & Clarkson, A. N. (2013). Perlecan domain V is neuroprotective and affords functional improvement in a photothrombotic stroke model in young and aged mice. Translational Stroke Research, 4, 515-523. doi: 10.1007/s12975-013-0266-1

Imhoff, F. M., Yang, D., Mathew, S. F., Clarkson, A. N., Kawagishi, Y., Tate, W. P., Koishi, K., & McLennan, I. S. (2013). The type 2 anti-Müllerian hormone receptor has splice variants that are dominant-negative inhibitors. FEBS Letters, 587(12), 1749-1753. doi: 10.1016/j.febslet.2013.04.014

Clarkson, A. N., López-Valdés, H. E., Overman, J. J., Charles, A. C., Brennan, K. C., & Carmichael, S. T. (2013). Multimodal examination of structural and functional remapping in the mouse photothrombotic stroke model. Journal of Cerebral Blood Flow & Metabolism, 33, 716-723. doi: 10.1038/jcbfm.2013.7

Overman, J. J., Clarkson, A. N., Wanner, I. B., Overman, W. T., Eckstein, I., Maguire, J. L., … Carmichael, S. T. (2012). A role for ephrin-A5 in axonal sprouting, recovery, and activity-dependent plasticity after stroke. PNAS, 109(33), E2230-E2239. doi: 10.1073/pnas.1204386109

Clarkson, A. N. (2012). Perisynaptic GABA receptors: The overzealous protector. Advances in Pharmacological Sciences, 2012, 708428. doi: 10.1155/2012/708428

Clarkson, A. N., Overman, J. J., Zhong, S., Mueller, R., Lynch, G., & Carmichael, S. T. (2011). AMPA receptor-induced local brain-derived neurotrophic factor signaling mediates motor recovery after stroke. Journal of Neuroscience, 31(10), 3766-3775. doi: 10.1523/JNEUROSCI.5780-10.2011

Sutherland, B. A., Shaw, O. M., Clarkson, A. N., Winburn, I. C., Errington, A. C., Dixon, C. L., Lees, G., Sammut, I. A., & Appleton, I. (2011). Tin protoporphyrin provides protection following cerebral hypoxia-ischemia: Involvement of alternative pathways. Journal of Neuroscience Research, 89(8), 1284-1294. doi: 10.1002/jnr.22661

Nair, S. M., Rahman, R. M. A., Clarkson, A. N., Sutherland, B. A., Taurin, S., Sammut, I. A., & Appleton, I. (2011). Melatonin treatment following stroke induction modulates L-arginine metabolism. Journal of Pineal Research, 51(3), 313-323. doi: 10.1111/j.1600-079X.2011.00891.x

Clarkson, A. N., Talbot, C. L., Wang, P.-Y., MacLaughlin, D. T., Donahoe, P. K., & McLennan, I. S. (2011). Müllerian inhibiting substance is anterogradely transported and does not attenuate avulsion-induced death of hypoglossal motor neurons. Experimental Neurology, 231(2), 304-308. doi: 10.1016/j.expneurol.2010.12.019

Clarkson, A. N., Huang, B. S., MacIsaac, S. E., Mody, I., & Carmichael, S. T. (2010). Reducing excessive GABA-mediated tonic inhibition promotes functional recovery after stroke. Nature, 468(7321), 305-309. doi: 10.1038/nature09511

Sutherland, B. A., Rahman, R. M. A., Clarkson, A. N., Shaw, O. M., Nair, S. M., & Appleton, I. (2009). Cerebral heme oxygenase 1 and 2 spatial distribution is modulated following injury from hypoxia-ischemia and middle cerebral artery occlusion in rats. Neuroscience Research, 65(4), 326-334. doi: 10.1016/j.neures.2009.08.007

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