Reduction in programmed cell death and improvement in functional outcome of transient focal cerebral ischemia after administration of granulocyte- macrophage colony-stimulating factor in rats: Laboratory investigation

Tae Ho Kong, Jung Kyoung Choi, Hyeonseon Park, Hyune Choi Byung, Brian Jeffrey Snyder, Shefqat Bukhari, Na Kyeong Kim, Xian Huang, Ra Park So, Chun Park Hyung, Yoon Ha

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

Object. Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a potent hematopoietic growth factor that both enhances the survival and drives the differentiation and proliferation of myeloid lineage cells. Recent studies have suggested that GM-CSF has a neuroprotective effect against CNS injury. In this paper, the authors investigated the neuroprotective effect of GM-CSF on neuron survival and locomotor behavior in a rat model of focal cerebral ischemic injury. Materials. To understand its neuroprotective effect in vitro, GM-CSF was administered to a glutamate-induced excitotoxicity neuronal injury cell culture model that mimics the pathophysiology of focal hypoxic cerebral injury. In the animal study, the authors prepared a rat focal cerebral ischemia model by occluding the unilateral middle cerebral artery. They then examined the effects of GM-CSF administration on changes in infarct volume, apoptosis-related gene expression, and improvement in locomotor behavior. Results. Treatment with GM-CSF significantly increased cell viability in a cell culture model of glutamate-induced neuronal injury. Furthermore, in vivo administration of GM-CSF at 60 μg/kg body weight daily for 5 consecutive days beginning immediately after injury decreased infarction volume, altered the expression of several apoptosis-related genes (Bcl-2, Bax, caspase 3, and p53), and improved locomotor behavior in the focal cerebral ischemia model. Conclusions. The GM-CSF had neuroprotective effects in in vitro and in vivo experiments and resulted in decreased infarction volume and improved locomotor behavior. Although the specific mechanism involved in stroke recovery was not fully elucidated as it was not the primary focus of this study, administration of GM-CSF appeared to decrease the extent of neuronal apoptosis by modulating the expression of several apoptosis-related genes such as Bcl-2, Bax, caspase 3, and p53. Further investigations are necessary to better understand the role of GM-CSF on neural regeneration during the recovery phase of a stroke, as well as the intracellular signal transduction pathways that mediate neuroprotection.

Original languageEnglish
Pages (from-to)155-163
Number of pages9
JournalJournal of neurosurgery
Volume111
Issue number1
DOIs
Publication statusPublished - 2009 Jul 1

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Transient Ischemic Attack
Granulocyte-Macrophage Colony-Stimulating Factor
Cell Death
Neuroprotective Agents
Wounds and Injuries
Apoptosis
Brain Ischemia
Caspase 3
Infarction
Glutamic Acid
Cell Culture Techniques
Stroke
bcl-2 Genes
Middle Cerebral Artery
Myeloid Cells
Regeneration
Signal Transduction
Cell Survival
Intercellular Signaling Peptides and Proteins
Body Weight

All Science Journal Classification (ASJC) codes

  • Surgery
  • Clinical Neurology

Cite this

Kong, Tae Ho ; Choi, Jung Kyoung ; Park, Hyeonseon ; Byung, Hyune Choi ; Snyder, Brian Jeffrey ; Bukhari, Shefqat ; Kim, Na Kyeong ; Huang, Xian ; So, Ra Park ; Hyung, Chun Park ; Ha, Yoon. / Reduction in programmed cell death and improvement in functional outcome of transient focal cerebral ischemia after administration of granulocyte- macrophage colony-stimulating factor in rats : Laboratory investigation. In: Journal of neurosurgery. 2009 ; Vol. 111, No. 1. pp. 155-163.
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abstract = "Object. Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a potent hematopoietic growth factor that both enhances the survival and drives the differentiation and proliferation of myeloid lineage cells. Recent studies have suggested that GM-CSF has a neuroprotective effect against CNS injury. In this paper, the authors investigated the neuroprotective effect of GM-CSF on neuron survival and locomotor behavior in a rat model of focal cerebral ischemic injury. Materials. To understand its neuroprotective effect in vitro, GM-CSF was administered to a glutamate-induced excitotoxicity neuronal injury cell culture model that mimics the pathophysiology of focal hypoxic cerebral injury. In the animal study, the authors prepared a rat focal cerebral ischemia model by occluding the unilateral middle cerebral artery. They then examined the effects of GM-CSF administration on changes in infarct volume, apoptosis-related gene expression, and improvement in locomotor behavior. Results. Treatment with GM-CSF significantly increased cell viability in a cell culture model of glutamate-induced neuronal injury. Furthermore, in vivo administration of GM-CSF at 60 μg/kg body weight daily for 5 consecutive days beginning immediately after injury decreased infarction volume, altered the expression of several apoptosis-related genes (Bcl-2, Bax, caspase 3, and p53), and improved locomotor behavior in the focal cerebral ischemia model. Conclusions. The GM-CSF had neuroprotective effects in in vitro and in vivo experiments and resulted in decreased infarction volume and improved locomotor behavior. Although the specific mechanism involved in stroke recovery was not fully elucidated as it was not the primary focus of this study, administration of GM-CSF appeared to decrease the extent of neuronal apoptosis by modulating the expression of several apoptosis-related genes such as Bcl-2, Bax, caspase 3, and p53. Further investigations are necessary to better understand the role of GM-CSF on neural regeneration during the recovery phase of a stroke, as well as the intracellular signal transduction pathways that mediate neuroprotection.",
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Reduction in programmed cell death and improvement in functional outcome of transient focal cerebral ischemia after administration of granulocyte- macrophage colony-stimulating factor in rats : Laboratory investigation. / Kong, Tae Ho; Choi, Jung Kyoung; Park, Hyeonseon; Byung, Hyune Choi; Snyder, Brian Jeffrey; Bukhari, Shefqat; Kim, Na Kyeong; Huang, Xian; So, Ra Park; Hyung, Chun Park; Ha, Yoon.

In: Journal of neurosurgery, Vol. 111, No. 1, 01.07.2009, p. 155-163.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Reduction in programmed cell death and improvement in functional outcome of transient focal cerebral ischemia after administration of granulocyte- macrophage colony-stimulating factor in rats

T2 - Laboratory investigation

AU - Kong, Tae Ho

AU - Choi, Jung Kyoung

AU - Park, Hyeonseon

AU - Byung, Hyune Choi

AU - Snyder, Brian Jeffrey

AU - Bukhari, Shefqat

AU - Kim, Na Kyeong

AU - Huang, Xian

AU - So, Ra Park

AU - Hyung, Chun Park

AU - Ha, Yoon

PY - 2009/7/1

Y1 - 2009/7/1

N2 - Object. Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a potent hematopoietic growth factor that both enhances the survival and drives the differentiation and proliferation of myeloid lineage cells. Recent studies have suggested that GM-CSF has a neuroprotective effect against CNS injury. In this paper, the authors investigated the neuroprotective effect of GM-CSF on neuron survival and locomotor behavior in a rat model of focal cerebral ischemic injury. Materials. To understand its neuroprotective effect in vitro, GM-CSF was administered to a glutamate-induced excitotoxicity neuronal injury cell culture model that mimics the pathophysiology of focal hypoxic cerebral injury. In the animal study, the authors prepared a rat focal cerebral ischemia model by occluding the unilateral middle cerebral artery. They then examined the effects of GM-CSF administration on changes in infarct volume, apoptosis-related gene expression, and improvement in locomotor behavior. Results. Treatment with GM-CSF significantly increased cell viability in a cell culture model of glutamate-induced neuronal injury. Furthermore, in vivo administration of GM-CSF at 60 μg/kg body weight daily for 5 consecutive days beginning immediately after injury decreased infarction volume, altered the expression of several apoptosis-related genes (Bcl-2, Bax, caspase 3, and p53), and improved locomotor behavior in the focal cerebral ischemia model. Conclusions. The GM-CSF had neuroprotective effects in in vitro and in vivo experiments and resulted in decreased infarction volume and improved locomotor behavior. Although the specific mechanism involved in stroke recovery was not fully elucidated as it was not the primary focus of this study, administration of GM-CSF appeared to decrease the extent of neuronal apoptosis by modulating the expression of several apoptosis-related genes such as Bcl-2, Bax, caspase 3, and p53. Further investigations are necessary to better understand the role of GM-CSF on neural regeneration during the recovery phase of a stroke, as well as the intracellular signal transduction pathways that mediate neuroprotection.

AB - Object. Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a potent hematopoietic growth factor that both enhances the survival and drives the differentiation and proliferation of myeloid lineage cells. Recent studies have suggested that GM-CSF has a neuroprotective effect against CNS injury. In this paper, the authors investigated the neuroprotective effect of GM-CSF on neuron survival and locomotor behavior in a rat model of focal cerebral ischemic injury. Materials. To understand its neuroprotective effect in vitro, GM-CSF was administered to a glutamate-induced excitotoxicity neuronal injury cell culture model that mimics the pathophysiology of focal hypoxic cerebral injury. In the animal study, the authors prepared a rat focal cerebral ischemia model by occluding the unilateral middle cerebral artery. They then examined the effects of GM-CSF administration on changes in infarct volume, apoptosis-related gene expression, and improvement in locomotor behavior. Results. Treatment with GM-CSF significantly increased cell viability in a cell culture model of glutamate-induced neuronal injury. Furthermore, in vivo administration of GM-CSF at 60 μg/kg body weight daily for 5 consecutive days beginning immediately after injury decreased infarction volume, altered the expression of several apoptosis-related genes (Bcl-2, Bax, caspase 3, and p53), and improved locomotor behavior in the focal cerebral ischemia model. Conclusions. The GM-CSF had neuroprotective effects in in vitro and in vivo experiments and resulted in decreased infarction volume and improved locomotor behavior. Although the specific mechanism involved in stroke recovery was not fully elucidated as it was not the primary focus of this study, administration of GM-CSF appeared to decrease the extent of neuronal apoptosis by modulating the expression of several apoptosis-related genes such as Bcl-2, Bax, caspase 3, and p53. Further investigations are necessary to better understand the role of GM-CSF on neural regeneration during the recovery phase of a stroke, as well as the intracellular signal transduction pathways that mediate neuroprotection.

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