Abstract

To develop new rehabilitation therapies for chronic stroke, this study examined the effectiveness of task-specific training (TST) and TST combined with DNA methyltransferase inhibitor in chronic stroke recovery. Eight weeks after photothrombotic stroke, 5-Aza-2′-deoxycytidine (5-Aza-dC) infusion was done on the contralesional cortex for four weeks, with and without TST. Functional recovery was assessed using the staircase test, the cylinder test, and the modified neurological severity score (mNSS). Axonal plasticity and expression of brain-derived neurotrophic factor (BDNF) were determined in the contralateral motor cortex. TST and TST combined with 5-Aza-dC significantly improved the skilled reaching ability in the staircase test and ameliorated mNSS scores and cylinder test performance. TST and TST with 5-Aza-dC significantly increased the crossing fibers from the contralesional red nucleus, reticular formation in medullar oblongata, and dorsolateral spinal cord. Mature BDNF was significantly upregulated by TST and TST combined with 5-Azd-dC. Functional recovery after chronic stroke may involve axonal plasticity and increased mature BDNF by modulating DNA methylation in the contralesional cortex. Our results suggest that combined therapy to enhance axonal plasticity based on TST and 5-Aza-dC constitutes a promising approach for promoting the recovery of function in the chronic stage of stroke.

Highlights

  • Stroke is the most common cause of long-term adult disability [1]

  • Our data showed that the expression of mature BDNF (mBDNF) was significantly increased by task-specific training (TST) and TST combined with 5-Aza-dC treatment after stroke

  • This study demonstrated the beneficial role of TST in motor recovery in the chronic stage after stroke

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Summary

Introduction

There is currently no specific treatment for improving functional recovery after stroke, except during rehabilitation. It is well known that rehabilitation plays a pivotal role in the functional motor recovery of patients with stroke [2,3]. Neurological recovery culminates within 1–3 months after stroke. Most spontaneous recovery occurs up to six months after the condition [1,2,3]. The Copenhagen stroke study found that 80% of patients with stroke attain good neurological outcome within 4.5 weeks of stroke, with time profiles varying according to the initial post-stroke severity [4]. An appropriate therapeutic period is very important for the restoration of function after stroke. There is a requirement for the improvement of effective therapeutic options that can enhance functional recovery in chronic stages after stroke

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