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Role of a Burr Hole and Calvarial Bone Marrow-Derived Stem Cells in the Ischemic Rat Brain : A Possible Mechanism for the Efficacy of Multiple Burr Hole Surgery in Moyamoya Disease

  • Nam, Taek-kyun (Department of Neurosurgery, Chung-Ang University College of Medicine) ;
  • Park, Seung-won (Department of Neurosurgery, Chung-Ang University College of Medicine) ;
  • Park, Yong-sook (Department of Neurosurgery, Chung-Ang University College of Medicine) ;
  • Kwon, Jeong-taik (Department of Neurosurgery, Chung-Ang University College of Medicine) ;
  • Min, Byung-kook (Department of Neurosurgery, Chung-Ang University College of Medicine) ;
  • Hwang, Sung-nam (Department of Neurosurgery, Chung-Ang University College of Medicine)
  • Received : 2015.03.08
  • Accepted : 2015.06.11
  • Published : 2015.10.28

Abstract

Objective : This study investigates the role of a burr hole and calvarial bone marrow-derived stem cells (BMSCs) in a transient ischemic brain injury model in the rat and postulates a possible mechanism for the efficacy of multiple cranial burr hole (MCBH) surgery in moyamoya disease (MMD). Methods : Twenty Sprague-Dawley rats (250 g, male) were divided into four groups : normal control group (n=5), burr hole group (n=5), ischemia group (n=5), and ischemia+burr hole group (n=5). Focal ischemia was induced by the transient middle cerebral artery occlusion (MCAO). At one week after the ischemic injury, a 2 mm-sized cranial burr hole with small cortical incision was made on the ipsilateral (left) parietal area. Bromodeoxyuridine (BrdU, 50 mg/kg) was injected intraperitoneally, 2 times a day for 6 days after the burr hole trephination. At one week after the burr hole trephination, brains were harvested. Immunohistochemical stainings for BrdU, CD34, VEGF, and Doublecortin and Nestin were done. Results : In the ischemia+burr hole group, BrdU (+), CD34 (+), and Doublecortin (+) cells were found in the cortical incision site below the burr hole. A number of cells with Nestin (+) or VEGF (+) were found in the cerebral parenchyma around the cortical incision site. In the other groups, BrdU (+), CD34 (+), Doublecortin (+), and Nestin (+) cells were not detected in the corresponding area. These findings suggest that BrdU (+) and CD34 (+) cells are bone marrow-derived stem cells, which may be derived from the calvarial bone marrow through the burr hole. The existence of CD34 (+) and VEGF (+) cells indicates increased angiogenesis, while the existence of Doublecortin (+), Nestin (+) cells indicates increased neurogenesis. Conclusion : Based on these findings, the BMSCs through burr holes seem to play an important role for the therapeutic effect of the MCBH surgery in MMD.

Keywords

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