Thrombin-induced microglial activation impairs hippocampal neurogenesis and spatial memory ability in mice

Behav Brain Funct. 2015 Sep 26;11(1):30. doi: 10.1186/s12993-015-0075-7.


Background: To investigate the effects of microglia/macrophages activation induced by intrastriatal thrombin injection on dentate gyrus neurogenesis and spatial memory ability in mice.

Methods: The male C57BL/6 mice were divided into 4 groups of 10: sham, intracerebral hemorrhage (ICH), ICH + hirudin (thrombin inhibitor), and ICH + indometacin (Indo, an anti-inflammation drug). ICH model was created by intrastriatal thrombin (1U) injection. BrdU (50 mg/kg) was administrated on the same day after surgery for 6 consecutive days. Motor functions were evaluated with rotarod and beam walking tests. The spatial memory deficit was measured with Morris water maze (MWM). Cell quantification was performed for doublecortin (DCX, immature neuron), BrdU (S-phase proliferating cell population) and CD68 (activated microglia/macrophage) immune-reactive cells.

Results: Microglia/macrophages activation induced by intrastriatal thrombin injection reduced hippocampal neurogenesis and impaired spatial memory ability, but did not affect the motor function at 3 and 5 days post-injury. Both hirudin and indometacin reduced microglia/macrophages activation, enhanced hippocampal neurogenesis, and improved spatial memory ability in mice.

Conclusions: Microglia/macrophages activation induced by intrastriatal thrombin injection might be responsible for the spatial memory deficit. Targeting both thrombin and inflammation systems in acute phase of ICH might be important in alleviating the significant spatial memory deficits.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Proliferation / drug effects
  • Cerebral Hemorrhage / chemically induced
  • Cerebral Hemorrhage / physiopathology
  • Cerebral Hemorrhage / psychology
  • Corpus Striatum / drug effects
  • Dentate Gyrus / drug effects*
  • Dentate Gyrus / pathology*
  • Doublecortin Protein
  • Hirudins / pharmacology
  • Indomethacin / pharmacology
  • Male
  • Maze Learning / drug effects
  • Mice
  • Microglia / drug effects*
  • Microinjections
  • Motor Skills / drug effects
  • Neurogenesis / drug effects*
  • Spatial Memory / drug effects*
  • Thrombin / administration & dosage
  • Thrombin / adverse effects*
  • Thrombin / antagonists & inhibitors


  • Dcx protein, mouse
  • Doublecortin Protein
  • Hirudins
  • Thrombin
  • Indomethacin