Transplantation of bone marrow stromal cells enhances nerve regeneration of the corticospinal tract and improves recovery of neurological functions in a collagenase-induced rat model of intracerebral hemorrhage

Mol Cells. 2013 Jul;36(1):17-24. doi: 10.1007/s10059-013-2306-9. Epub 2013 Jun 25.

Abstract

The reorganization of brain structures after intracerebral hemorrhage (ICH) insult is crucial to functional outcome. Although the pattern of neuronal rewiring is well-documented after ischemic stroke, the study of brain plasticity after ICH has been focusing on the enhancement of dendritic complexity. Here we hypothesized that functional restoration after ICH involves brain reorganization which may be favorably modulated by stem cell transplantation. In this study, bone marrow stromal cells (BMSCs) were transplanted into the perilesional sites of collagenase-induced ICH in adult rats one day after ICH injury. Forelimb functional recovery was monitored with modified limb placing and vibrissae-elicited forelimb placement tests. Anterograde and retrograde tracing were used to assess the reorganization of bilateral forelimb areas of the sensorimotor cortex. We found that in rats transplanted with BMSCs after ICH injury, axonal sprouting occurred in the contralateral caudal forelimb area of the cortex, and was significantly higher than in ICH rat models that received only the vehicle (P < 0.01). The number of positive neurons in the ipsilateral rostral forelimb area of the cortex of the BMSC group was 1.5-to 4.5-fold greater than in the vehicle group (P < 0.05). No difference was found between the BMSC and vehicle groups in hemispheric atrophy or labeled neurons in the ipsilateral caudal forelimb area (P = 0.193). Scores for improved functional behavior in the BMSC group were in accord with the results from histology. Neuronal plasticity of the denervated corticospinal tract at bilateral forelimb areas of the cortex in the collagenase-induced ICH rat models was significantly enhanced by BMSC transplantation. BMSC transplantation may facilitate functional recovery after ICH injury.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Atrophy
  • Bone Marrow Cells / cytology*
  • Cell Movement
  • Cell Survival
  • Cerebral Hemorrhage / physiopathology*
  • Cerebral Hemorrhage / therapy*
  • Cerebrum / pathology
  • Cerebrum / physiopathology
  • Collagenases
  • Disease Models, Animal
  • Female
  • Forelimb / physiopathology
  • Male
  • Nerve Regeneration*
  • Neurons / metabolism
  • Neurons / pathology
  • Pyramidal Tracts / physiopathology*
  • Rats
  • Rats, Wistar
  • Recovery of Function / physiology*
  • Staining and Labeling
  • Stilbamidines / metabolism
  • Stromal Cells / transplantation

Substances

  • 2-hydroxy-4,4'-diamidinostilbene, methanesulfonate salt
  • Stilbamidines
  • Collagenases