Functional Improvement after Photothrombotic Stroke in Rats Is Associated with Different Patterns of Dendritic Plasticity after G-CSF Treatment and G-CSF Treatment Combined with Concomitant or Sequential Constraint-Induced Movement Therapy

PLoS One. 2016 Jan 11;11(1):e0146679. doi: 10.1371/journal.pone.0146679. eCollection 2016.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Combined Modality Therapy
  • Dendrites / drug effects
  • Dendrites / pathology*
  • Granulocyte Colony-Stimulating Factor / pharmacology
  • Light*
  • Male
  • Movement
  • Neuronal Plasticity* / drug effects
  • Physical Therapy Modalities*
  • Pyramidal Cells / drug effects
  • Pyramidal Cells / metabolism
  • Pyramidal Cells / pathology
  • Rats, Wistar
  • Recovery of Function* / drug effects
  • Stroke / physiopathology*
  • Stroke / therapy*

Substances

  • Granulocyte Colony-Stimulating Factor

Grants and funding

CS and WRS were supported from a grant by the German Research Foundation (Deutsche Forschungsgemeinschaft, DFG; SO 908/3-1, SCH 787/5-1). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.