Tamoxifen favoured the rat sensorial cortex regeneration after a penetrating brain injury

Brain Res Bull. 2013 Sep:98:64-75. doi: 10.1016/j.brainresbull.2013.07.007. Epub 2013 Jul 23.

Abstract

A penetrating brain injury produces a glial scar formed by astrocytes, oligodendrocytes, microglia and NG2 cells. Glial scar is a barrier preventing the extent of damage but it has deleterious effects in the regeneration of the axons. Estradiol and tamoxifen reduce gliosis and have neuroprotective effects in the hippocampus and the spinal cord. We evaluated the proliferation of glia and the electrocorticogram in the sensorial cortex in a brain injury model. At seven days post-injury, estradiol, tamoxifen and estradiol plus tamoxifen reduced the number of resident and proliferative NG2 and reactive astrocyte vimentin+ cells. Estradiol and tamoxifen effects on NG2 cells could be produced by the classical oestrogen receptors found in these cells. The glial scar was also reduced by tamoxifen. At thirty days post-injury, the amount of resident and proliferative astrocytes increased significantly, except in the estradiol plus tamoxifen group, whilst the oligodendrocytes proliferation in the glial scar was reduced in treated animals. Tamoxifen promotes the survival of FOX-3+ neurons in the injured area and a recovery in the amplitude of electrocorticogram waves. At thirty days, estradiol did not favour the survival of neurons but produced a greater number of reactive astrocytes. In contrast, the number of oligodendrocytes was reduced. Tamoxifen could favour brain repair promoting neuron survival and adjusting glial cell number. It seems to recover adequate neural communication.

Keywords: 17β-estradiol; 17β-estradiol plus tamoxifen; 5-bromo-2-deoxy-uridine; 60min post-injury; 60mpi; BrdU; CTL; E2; E2+TAM; ECoG; ERα; ERβ; Electrocorticogram; Estradiol; GFAP; IL-1β; IL-6; IP-10; MAG; OMgp; PBS; PKC; Penetrating brain injury; SERM; TAM; Tamoxifen; VEH-INJ; control; electrocorticogram; glial fibrilar acidic protein; glycoprotein associated to myelin; interferon-gamma-inducible protein-10; interleukin 1 beta; interleukin 6; oestrogen receptor alpha; oestrogen receptor beta; oligodendrocytes myelin glycoprotein; phosphate buffer saline; protein kinase C; selective oestrogen receptor modulator; tamoxifen; vehicle injured.

MeSH terms

  • Animals
  • Antigens / metabolism
  • Astrocytes / drug effects
  • Astrocytes / metabolism
  • Brain Waves / drug effects
  • Disease Models, Animal
  • Head Injuries, Penetrating / drug therapy
  • Head Injuries, Penetrating / pathology*
  • Male
  • Nerve Tissue Proteins / metabolism
  • Neurons / drug effects
  • Neurons / metabolism
  • Proteoglycans / metabolism
  • Rats
  • Rats, Wistar
  • Receptors, Estrogen / metabolism
  • Regeneration / drug effects*
  • Selective Estrogen Receptor Modulators / therapeutic use*
  • Somatosensory Cortex / drug effects*
  • Somatosensory Cortex / physiopathology
  • Tamoxifen / therapeutic use*
  • Time Factors

Substances

  • Antigens
  • Nerve Tissue Proteins
  • Proteoglycans
  • Receptors, Estrogen
  • Selective Estrogen Receptor Modulators
  • chondroitin sulfate proteoglycan 4
  • Tamoxifen