Reduction of Brain Injury in Neonatal Hypoxic–Ischemic Rats by Intracerebroventricular Injection of Neural Stem/Progenitor Cells Together With Chondroitinase ABC Yoshiaki Sato, MD, PhD, Keiko Nakanishi, MD, PhD, Masahiro Hayakawa, MD, PhD, Hiroko Kakizawa, MD, PhD,Akiko Saito, MD, Yoshiyuki Kuroda, Michiru Ida, PhD,Yoshihito Tokita, PhD, Sachiko Aono, PhD, Fumiko Matsui, PhD, Seiji Kojima MD, PhD, and Atsuhiko Oohira, PhD  Perinatal hypoxia–ischemia (HI) remains a critical issue. Cell transplantation therapy could be a potent treatment for many neurodegenerative diseases, but limited works on this kind of therapy have been reported for perinatal HI. In this study, the therapeutic effect of transplantation with neural stem/ progenitor cells (NSPCs) and chondrotinase ABC (ChABC) in a neonatal HI rat model is evaluated. Histological studies showed that the unaffected area of the brain in animals treated with NSPCs together with ChABC was significantly larger than that in the animals treated with vehicle or NSPCs alone. The wet weight of the brain that received the combined treatment was also significantly higher than those of the vehicle and their individual treatments. These results indicate that intracerebroventric- ular injection of NSPCs with ChABC reduces brain injury in a rat neonatal HI model.  KEY WORDS: Neonatal hypoxia–ischemia, neural stem/progenitor cells, chondroitin sulfate, chondroitinase ABC. millions of neonatal deaths and neurological disadvan- tages. 1-4 However, no effective treatments have been established against brain damage induced by HI except brain hypothermia, 5,6 which is not effective for severe HI. Therefore,it is urgent to develop a novel therapy against brain injury associated with HI. Stem cells are derived from various tissues including fetal brains and are defined by their properties of self- renewal and multipotency.They are capable of generating committed progenitor cells to variable degrees and ulti- mately differentiating into mature cells. Cell transplanta- tion therapy, including the use of embryonic stem (ES) cells, neural stem/progenitor cells (NSPCs), bone mar- row stromal cells, and umbilical cord blood cells, are potential treatments for many neurodegenerative diseases: Huntington’s disease (HD), Parkinson’s disease (PD), amyotrophic lateral sclerosis, multiple sclerosis, stroke, spinal cord injury, and perinatal HI. Recently, a number of studies with adult animal models of these neurological diseases revealed that transplantation of these cells could achieve functional recovery. 7-10 Based on these results, clinical trials have been carried out in patients affected by P erinatal hypoxia-ischemia (HI) remains an impor- tant cause of death and permanent neuropsycho- logic deficits. It has been estimated that HI injury occurs in approximately 2 to 4 out of 1000 live births of term infants in developed countries, and is 20 to 30 times higher in developing countries. Perinatal HI leads to From the Department of Perinatology,Institute for Developmental Research, Aichi Human Service Center, Kasugai,Aichi, Japan (YS, KN, HK,AS,YK, MI, YT, SA, FM, AO); Department of Pediatrics, Nagoya University Graduate School of Medicine, Nagoya, Japan (YS, HK, AS, SK); Department of Neonatology, Central Hospital, Aichi Human Service Center, Kasugai, Aichi, Japan (YS); and Maternity and Perinatal Care Center, Nagoya University Hospital, Nagoya, Japan (MH). This work was supported in part by grants-in-aid for scientific research from the Ministry of Education, Culture, Sports, Science, and Technology of Japan and from the Japan Society for the Promotion of Science. Address correspondence to:Atsuhiko Oohira, PhD, Research Complex for the Medicine Frontiers,Aichi Medical University, 21 Karimata,Yazako, Nagakute, Aichi 480-1195, Japan. E-mail: atsu48@aichi-med-u.ac.jp. Reproductive Sciences Vol. 15 No. 6 July 2008 613-620 DOI. 10.1177/1933719108317299 © 2008 by the Society for Gynecologic Investigation 613