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
Publications
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
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
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. Advance online publication. doi: 10.1007/s12017-019-08557-3
Clarkson, A. N., Barwick, D. K., Zubkova, O., & Carmichael, S. T. (2019). Combined treatment of rehabilitation and novel glycosominoglycan treatment abolishes forelimb impiarments following motor cortex stroke in mice. Journal of Cerebral Blood Flow & Metabolism, 39(1, Suppl.), (pp. 458-459). doi: 10.1177/0271678X19851020
Clarkson, A. N., & Houlton, J. (2019). BDNF improves cognitive function after stroke in aged mice. Journal of Cerebral Blood Flow & Metabolism, 39(1, Suppl.), (pp. 344). doi: 10.1177/0271678X19851020
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 GABAA 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.
Journal - Research Article
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. Advance online publication. 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
Clarkson, A. N., Boothman-Burrell, L., Dósa, Z., Nagaraja, R. Y., Jin, L., Parker, K., … Neumann, S., Gowing, E. K., … Chebib, M. (2018). The flavonoid, 2'-methoxy-6-methylflavone, affords neuroprotection following focal cerebral ischaemia. Journal of Cerebral Blood Flow & Metabolism. Advance online publication. doi: 10.1177/0271678x18755628
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. Advance online publication. doi: 10.1152/jn.00167.2018
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
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
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. Advance online publication. 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
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. Advance online publication. doi: 10.1016/j.neuroscience.2018.07.034
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 GABAA 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
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
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
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
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
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
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
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
Wang, P.-Y., Protheroe, A., Clarkson, A. N., Imhoff, F., Koishi, K., & McLennan, I. S. (2009). Müllerian inhibiting substance contributes to sex-linked biases in the brain and behavior. PNAS, 106(17), 7203-7208. doi: 10.1073/pnas.0902253106
Pugazhenthi, K., Kapoor, M., Clarkson, A. N., Hall, I., & Appleton, I. (2008). Melatonin accelerates the process of wound repair in full-thickness incisional wounds. Journal of Pineal Research, 44(4), 387-396. doi: 10.1111/j.1600-079X.2007.00541.x
Vranyac-Tramoundanas, A., Harrison, J. C., Clarkson, A. N., Kapoor, M., Winburn, I. C., Kerr, D. S., & Sammut, I. A. (2008). Domoic acid impairment of cardiac energetics. Toxicological Sciences, 105(2), 395-407. doi: 10.1093/toxsci/kfn132
Hesp, B. R., Clarkson, A. N., Sawant, P. M., & Kerr, D. S. (2007). Domoic acid preconditioning and seizure induction in young and aged rats. Epilepsy Research, 76, 103-112.
Clarkson, A. N., Liu, H., Schiborra, F., Shaw, O., Sammut, I. A., Jackson, D. M., & Appleton, I. (2007). Angiogenesis as a predictive marker of neurological outcome following hypoxia-ischemia. Brain Research, 1171, 111-121.
Clarkson, A. N., Clarkson, J., Jackson, D. M., & Sammut, I. A. (2007). Mitochondrial involvement in transhemispheric diaschisis following hypoxia-ischemia: Clomethiazole-mediated amelioration. Neuroscience, 144, 547-561.
Clarkson, A. N., Liu, H., Rahman, R., Jackson, D. M., Appleton, I., & Kerr, D. S. (2005). Clomethiazole: Mechanisms underlying lasting neuroprotection after hypoxia-ischemia. FASEB Journal, 19(8), 1036-1038.
Ashton, J. C., Khalessi, A., Kapoor, M., Clarkson, A., Sammut, I. A., Darlington, C. L., & Smith, P. F. (2005). Characterization of mitochondrial respiratory chain energetics in the vestibular nucleus complex [Short Communication]. Acta Oto-Laryngologica, 125, 422-425.
Sutherland, B. A., Shaw, O. M., Clarkson, A. N., Jackson, D. M., Sammut, I. A., & Appleton, I. (2005). Neuroprotective effects of (-)-epigallocatechin gallate following hypoxia-ischemia-induced brain damage: Novel mechanisms of action. FASEB Journal, 19(2), 258-260. doi: 10.1096/fj.04-2806fje
Clarkson, A. N., Sutherland, B. A., & Appleton, I. (2005). The biology and pathology of hypoxia-ischemia: An update. Archivum Immunologiae et Therapiae Experimentalis, 53, 213-225.
