Expression of brain-specific angiogenesis inhibitor 2 (BAI2) in normal and ischemic brain: involvement of BAI2 in the ischemia-induced brain angiogenesis

J Cereb Blood Flow Metab. 2002 Sep;22(9):1054-67. doi: 10.1097/00004647-200209000-00003.


Previously, the authors cloned and characterized murine brain-specific angiogenesis inhibitor 1 (mBAI1). In this study, the authors cloned mBAI2 and analyzed its functional characteristics. Northern and Western blot analyses demonstrated a unique developmental expression pattern of mBAI2 in the brain. The expression level of mBAI2 appeared to increase as the development of the brain progressed. Reverse transcription-polymerase chain reaction (RT-PCR) analyses demonstrated the existence of alternative splice variants of mBAI2, which were defective in parts of type I repeat of thrombospondin or the third cytoplasmic loop of the seven-span transmembrane domain that were considered essential to the functions of mBAI2. The expressions of spliced variants in the brain were differently regulated compared with wild-type mBAI2 during development and ischemic conditions. In situ hybridization analyses of the brain showed the same localization of BAI2 as BAI1, such as in most neurons of cerebral cortex. In the in vivo focal cerebral ischemia model and the in vitro hypoxic cell culture model with cobalt, BAI2 expression decreased after hypoxia and preceded the increased expression of vascular endothelial growth factor (VEGF). RT-PCR analysis of antisense BAI2 cDNA-transfected SHSY5Y cells showed an increased VEGF expression as well as a decreased BAI2 expression. Immunohistochemical study of focal ischemic cortex showed that the regional localization of decreased BAI2 was related to the formation of new vessels. These results suggest that the brain-specific developmental expression pattern of angiostatic BAI2 is correlated with the decreased neovascularization in the adult brain, and that angiostatic BAI2 participates in the ischemia-induced brain angiogenesis in concert with angiogenic VEGF.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Brain / metabolism*
  • Brain Ischemia / metabolism*
  • Cell Line
  • Cloning, Molecular
  • DNA Primers
  • DNA, Complementary / genetics
  • Endothelial Growth Factors / genetics
  • Humans
  • Lymphokines / genetics
  • Membrane Proteins
  • Mice
  • Models, Molecular
  • Molecular Sequence Data
  • Neovascularization, Physiologic / physiology*
  • Nerve Tissue Proteins / chemistry
  • Nerve Tissue Proteins / genetics*
  • Organ Specificity
  • Plasmids
  • Protein Conformation
  • RNA, Messenger / genetics
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sequence Alignment
  • Sequence Homology, Amino Acid
  • Transcription, Genetic*
  • Transfection
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors


  • ADGRB2 protein, human
  • Adgrb2 protein, mouse
  • Adgrb3 protein, mouse
  • DNA Primers
  • DNA, Complementary
  • Endothelial Growth Factors
  • Lymphokines
  • Membrane Proteins
  • Nerve Tissue Proteins
  • RNA, Messenger
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors