title: 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.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Neurosurgery, Chung-Ang University College of Medicine, Seoul, Korea.
authors.forename: Taek-Kyun
authors.initials: TK
authors.lastname: Nam
authors.affiliation: Department of Neurosurgery, Chung-Ang University College of Medicine, Seoul, Korea.
authors.forename: Seung-Won
authors.initials: SW
authors.lastname: Park
authors.affiliation: Department of Neurosurgery, Chung-Ang University College of Medicine, Seoul, Korea.
authors.forename: Yong-Sook
authors.initials: YS
authors.lastname: Park
authors.affiliation: Department of Neurosurgery, Chung-Ang University College of Medicine, Seoul, Korea.
authors.forename: Jeong-Taik
authors.initials: JT
authors.lastname: Kwon
authors.affiliation: Department of Neurosurgery, Chung-Ang University College of Medicine, Seoul, Korea.
authors.forename: Byung-Kook
authors.initials: BK
authors.lastname: Min
authors.affiliation: Department of Neurosurgery, Chung-Ang University College of Medicine, Seoul, Korea.
authors.forename: Sung-Nam
authors.initials: SN
authors.lastname: Hwang
keywords: Angiogenesis; Bone marrow; Burr hole; Moyamoya disease; Neurogenesis; Stem cell