Stroke recovery in rats after 24h-delayed intramuscular neurotrophin-3 infusion : WestminsterResearch

Publication dates
Title	Stroke recovery in rats after 24h-delayed intramuscular neurotrophin-3 infusion
Type	Journal article
Authors	Duricki, D.A., Drndarski, S., Bernanos, B., Tobias Wood, T., Bosch, K., Chen, Q., Shine, H.D., Simmons, C., Williams, S.C.R., McMahon, S.B., Begley, D.J., Cash, D. and Moon, L.D.F.
Abstract	Objective Neurotrophin‐3 (NT3) plays a key role in the development and function of locomotor circuits including descending serotonergic and corticospinal tract axons and afferents from muscle and skin. We have previously shown that gene therapy delivery of human NT3 into affected forelimb muscles improves sensorimotor recovery after stroke in adult and elderly rats. Here, to move toward the clinic, we tested the hypothesis that intramuscular infusion of NT3 protein could improve sensorimotor recovery after stroke. Methods Rats received unilateral ischemic stroke in sensorimotor cortex. To simulate a clinically feasible time to treatment, 24 hours later rats were randomized to receive NT3 or vehicle by infusion into affected triceps brachii for 4 weeks using implanted catheters and minipumps. Results Radiolabeled NT3 crossed from the bloodstream into the brain and spinal cord in rodents with or without strokes. NT3 increased the accuracy of forelimb placement during walking on a horizontal ladder and increased use of the affected arm for lateral support during rearing. NT3 also reversed sensory impairment of the affected wrist. Functional magnetic resonance imaging during stimulation of the affected wrist showed spontaneous recovery of peri‐infarct blood oxygenation level–dependent signal that NT3 did not further enhance. Rather, NT3 induced neuroplasticity of the spared corticospinal and serotonergic pathways. Interpretation Our results show that delayed, peripheral infusion of NT3 can improve sensorimotor function after ischemic stroke. Phase I and II clinical trials of NT3 (for constipation and neuropathy) have shown that peripheral high doses are safe and well tolerated, which paves the way for NT3 as a therapy for stroke.
Journal	Annals of Neurology
Journal citation	85 (1), pp. 32-46
ISSN	0364-5134
Year	2019
Publisher	Wiley
Publisher's version	Duricki, 2019.pdf License CC BY 4.0 File Access Level Open (open metadata and files)
Digital Object Identifier (DOI)	https://doi.org/10.1002/ana.25386
PubMed ID	30525223
Published online	07 Dec 2018
Published in print	Jan 2019

Related outputs

The Blood-Brain Barrier in Psychosis
Pollak, T.A., Drndarski, S., Stone, M.J., David, A.S., McGuire, P. and Abbott, N.J. 2018. The Blood-Brain Barrier in Psychosis. The Lancet Psychiatry. 5 (1), pp. 79-92. https://doi.org/10.1016/S2215-0366(17)30293-6

Heat shock protein–based therapy as a potential candidate for treating the sphingolipidoses
Kirkegaard, T., Gray, J., Priestman, D.A., Wallom, K.-L., Atkins, J., Olsen, O.D., Klein, A., Drndarski, S., Petersen, N.H.T., Ingemann, L., Smith, D.A., Morris, L., Bornæs, C., Jørgensen, S.H., Williams, I., Hinsby, A., Arenz, C., Begley, D., Jäättelä, M. and Platt, F.M. 2016. Heat shock protein–based therapy as a potential candidate for treating the sphingolipidoses. Science Translational Medicine. 8 (355), p. 355ra188 355ra188. https://doi.org/10.1126/scitranslmed.aad9823

An Improved in Vitro Blood-Brain Barrier Model: Rat Brain Endothelial Cells Co-Cultured With Astrocytes
Abbott, N.J., Dolman, D.E.M., Drndarski, S. and Fredriksson, S.M. 2012. An Improved in Vitro Blood-Brain Barrier Model: Rat Brain Endothelial Cells Co-Cultured With Astrocytes. Methods in Molecular Biology. 814, pp. 415-430. https://doi.org/10.1007/978-1-61779-452-0_28

Interaction between src family kinases and rho-kinase in agonist-induced Ca2+-sensitization of rat pulmonary artery
Knock, G.A., Shaifta, Y., Snetkov, V.A., Vowles, B., Drndarski, S., Ward, J.P. and Aaronson, P.I. 2008. Interaction between src family kinases and rho-kinase in agonist-induced Ca2+-sensitization of rat pulmonary artery. Cardiovascular Research. 77 (3), pp. 570-9. https://doi.org/10.1093/cvr/cvm073

Role of SRC-Family Kinases in Hypoxic Vasoconstriction of Rat Pulmonary Artery
Knock, G.A., Snetkov, V.A., Shaifta, Y., Drndarski, S., Ward, J.P. and Aaronson, P.I. 2008. Role of SRC-Family Kinases in Hypoxic Vasoconstriction of Rat Pulmonary Artery. Cardiovascular Research. 80 (3), pp. 453-62. https://doi.org/10.1093/cvr/cvn209

Constriction of Pulmonary Artery by Peroxide: Role of Ca2+ Release and PKC
Pourmahram, G.E., Snetkov, V.A., Shaifta, Y., Drndarski, S., Knock, G.A., Aaronson, P.I. and Ward, J.P. 2008. Constriction of Pulmonary Artery by Peroxide: Role of Ca2+ Release and PKC. Free Radical Biology & Medicine. 45 (10), pp. 1468-76. https://doi.org/10.1016/j.freeradbiomed.2008.08.020

Induction of Aquaporin 1 but Not Aquaporin 4 Messenger RNA in Rat Primary Brain Microvessel Endothelial Cells in Culture
Dolman, D.E.M., Drndarski, S., Abbott, N.J. and Rattray, M. 2005. Induction of Aquaporin 1 but Not Aquaporin 4 Messenger RNA in Rat Primary Brain Microvessel Endothelial Cells in Culture. Journal of Neurochemistry. 93 (4), pp. 825-833. https://doi.org/10.1111/j.1471-4159.2005.03111.x

Permalink - https://westminsterresearch.westminster.ac.uk/item/qzq96/stroke-recovery-in-rats-after-24h-delayed-intramuscular-neurotrophin-3-infusion

Stroke recovery in rats after 24h-delayed intramuscular neurotrophin-3 infusion

Related outputs

Share this

Usage statistics

Export as