Abstract

We have previously shown that granulocyte-colony stimulating factor (G-CSF) treatment alone, or in combination with constraint movement therapy (CIMT) either sequentially or concomitantly, results in significantly improved sensorimotor recovery after photothrombotic stroke in rats in comparison to untreated control animals. CIMT alone did not result in any significant differences compared to the control group (Diederich et al., Stroke, 2012;43:185–192). Using a subset of rat brains from this former experiment the present study was designed to evaluate whether dendritic plasticity would parallel improved functional outcomes. Five treatment groups were analyzed (n = 6 each) (i) ischemic control (saline); (ii) CIMT (CIMT between post-stroke days 2 and 11); (iii) G-CSF (10 μg/kg G-CSF daily between post-stroke days 2 and 11); (iv) combined concurrent group (CIMT plus G-CSF) and (v) combined sequential group (CIMT between post-stroke days 2 and 11; 10 μg/kg G-CSF daily between post-stroke days 12 and 21, respectively). After impregnation of rat brains with a modified Golgi-Cox protocol layer V pyramidal neurons in the peri-infarct cortex as well as the corresponding contralateral cortex were analyzed. Surprisingly, animals with a similar degree of behavioral recovery exhibited quite different patterns of dendritic plasticity in both peri-lesional and contralesional areas. The cause for these patterns is not easily to explain but puts the simple assumption that increased dendritic complexity after stroke necessarily results in increased functional outcome into perspective.

Highlights

  • Stroke is the leading cause of long-term disability in adulthood [1]

  • Both motor and somatosensory recovery was significantly increased at 28 days after stroke in the granulocyte-colony stimulating factor (G-CSF) treated group and in the two groups with a combination of concomitant or sequential treatment with G-CSF and constraint movement therapy (CIMT) compared to untreated ischemic controls

  • Dendritic plasticity of layer V pyramidal neurons was analyzed in the peri-infarct cortex and the corresponding contralateral cortex in each treatment group (Fig 1)

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Summary

Introduction

Stroke is the leading cause of long-term disability in adulthood [1]. Apart from thrombolysis or mechanical removal of the thromboembolic material occluding the vessel lumen no specific therapy is available yet [2, 3]. The effectivity of neuroprotective strategies for the treatment of ischemic stroke strongly depends on a prompt initiation of treatment which is one of the many problems preventing successful translation into the clinic up to now. Neurorestorative therapies have the attractive advantage of an extended time window to beneficially modulate brain regeneration after stroke. Positive effects have been described even when treatment was started with a delay of one month [4]. To further enhance the benefit of restorative therapies a combination of divergent therapeutic approaches to potentiate the success rate seems a promising strategy. There exist few studies which systematically addressed this issue

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