The effect of granulocyte-colony stimulating factor in global cerebral ischemia in rats

Gerald A. Matchett, Jason B. Calinisan, Genoveve C. Matchett, Robert D. Martin, John H. Zhang

Research output: Contribution to journalArticle

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Abstract

Granulocyte-colony stimulating factor (G-CSF) is an endogenous peptide hormone of the hematopoietic system that has entered Phase I/II clinical trials for treatment of ischemic stroke. Severe intraoperative hypotension can lead to global cerebral ischemia and apoptotic neuron loss within the hippocampus. We tested G-CSF in a rat model of global cerebral ischemia. Global cerebral ischemia was induced in male Sprague-Dawley rats (280-330 g) with the 2-vessel occlusion model (hemorrhagic hypotension to a mean arterial pressure of 30-35 mm Hg and bilateral common carotid artery occlusion for 8 min). Three groups of animals were used: global ischemia without treatment (GI, n = 49), global ischemia with G-CSF treatment (GI + G-CSF, n = 42), and sham surgery (Sham, n = 26). Rats in the treatment group received G-CSF (50 μg/kg, subcutaneously) 12 h before surgery, on the day of surgery, and on postoperative Day 1 and were euthanized on Days 2, 3, and 14. Mild hyperglycemia was observed in all groups. T-maze testing for spontaneous alternation demonstrated initial improvement in the G-CSF treatment group but no long-term benefit. Measurement of daily body weight demonstrated an initial trend toward improvement in the G-CSF group. Quantitative Nissl histology of the hippocampus demonstrated equivalent outcomes on Days 3 and 14, which was supported by quantitative TUNEL stain. Immunohistochemistry and Western blot demonstrated an initial increase in phosphorylated-AKT in the GI + G-CSF group on Day 2. We conclude that G-CSF treatment is associated with transient early improvement in neurobehavioral outcomes after global ischemia complicated by mild hyperglycemia, but no long-term protection.

Original languageEnglish (US)
Pages (from-to)200-207
Number of pages8
JournalBrain Research
Volume1136
Issue number1
DOIs
StatePublished - Mar 9 2007

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Granulocyte Colony-Stimulating Factor
Brain Ischemia
Ischemia
Hyperglycemia
Hypotension
Hippocampus
Therapeutics
Hematopoietic System
Phase II Clinical Trials
Clinical Trials, Phase I
Peptide Hormones
Common Carotid Artery
In Situ Nick-End Labeling
Ambulatory Surgical Procedures
Sprague Dawley Rats
Histology
Arterial Pressure
Coloring Agents
Western Blotting
Immunohistochemistry

Keywords

  • CA-1
  • G-CSF
  • Global ischemia
  • Hippocampus

ASJC Scopus subject areas

  • Neuroscience(all)
  • Clinical Neurology
  • Developmental Biology
  • Molecular Biology

Cite this

The effect of granulocyte-colony stimulating factor in global cerebral ischemia in rats. / Matchett, Gerald A.; Calinisan, Jason B.; Matchett, Genoveve C.; Martin, Robert D.; Zhang, John H.

In: Brain Research, Vol. 1136, No. 1, 09.03.2007, p. 200-207.

Research output: Contribution to journalArticle

Matchett, Gerald A. ; Calinisan, Jason B. ; Matchett, Genoveve C. ; Martin, Robert D. ; Zhang, John H. / The effect of granulocyte-colony stimulating factor in global cerebral ischemia in rats. In: Brain Research. 2007 ; Vol. 1136, No. 1. pp. 200-207.
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