Combination therapy of the granulocyte colony stimulating factor and intravenous lipid emulsion protect the hippocampus after global ischemia in rat: focusing on CA1 region

Metab Brain Dis. 2020 Aug;35(6):991-997. doi: 10.1007/s11011-020-00579-2. Epub 2020 May 26.

Abstract

Brain stroke is one of the causes of human death and disability worldwide. Global ischemia results in the accumulation of free radicals in the neurons. It leads to histologically brain damage. The CA1 region of the hippocampus is a sensitive area for free radicals. This study investigated the combined therapy of the Granulocyte colony stimulating factor (G-CSF) and the Intravenous lipid emulsion (ILE). These neuroprotective agents play a role in the regeneration of neurons. They improve the learning ability and memory in rats induced global ischemia. We divided 35 rats into five groups. The groups were sham group, ischemia group, G-CSF group, ILE group, and G-CSF plus ILE group. Ischemia was induced by occlusion of the bilateral common carotid about 10 min. The drugs applied on days 1, 3 and 7. The treated groups received subcutaneous injection of 20 μg/kg G-CSF and intravenous injection of 5 ml/kg ILE. After two weeks, the memory and learning ability of the rats was evaluated by the shuttle box. Hematoxylin and Eosin and Nissl and TUNEL stainings were used to determine the necrosis, normal and apoptotic cells. The combined therapy increased normal cells compared to the ischemia group. They decreased the number of necrotic and apoptosis cells in other groups. The combined group improved the passive avoidance test compared to the other groups. The combination therapy of G-CSF plus ILE is more effective than each alone.

Keywords: Global ischemia; Granulocyte colony stimulating factor; Intravenous lipid emulsion; Neuroprotection; Rat.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Avoidance Learning / drug effects
  • Avoidance Learning / physiology
  • Brain Ischemia / drug therapy*
  • Brain Ischemia / metabolism
  • Brain Ischemia / pathology
  • CA1 Region, Hippocampal / drug effects*
  • CA1 Region, Hippocampal / metabolism
  • CA1 Region, Hippocampal / pathology
  • Drug Therapy, Combination
  • Fat Emulsions, Intravenous / administration & dosage*
  • Granulocyte Colony-Stimulating Factor / administration & dosage*
  • Male
  • Neuroprotective Agents / administration & dosage*
  • Rats
  • Rats, Wistar

Substances

  • Fat Emulsions, Intravenous
  • Neuroprotective Agents
  • Granulocyte Colony-Stimulating Factor