Temporal profile of thrombogenesis in the cerebral microcirculation after traumatic brain injury in mice

J Neurotrauma. 2010 Jan;27(1):121-30. doi: 10.1089/neu.2009.1114.


Traumatic brain injury (TBI) is associated with an almost immediate reduction in cerebral blood flow (CBF). Because cerebral perfusion pressure is often normal under these circumstances it was hypothesized that the reduction of post-traumatic CBF has to occur at the level of the microcirculation. The aim of the current study was to investigate whether cerebral microvessels are involved in the development of blood flow disturbances following experimental TBI. C57/BL6 mice (n = 12) were intubated and ventilated under control of end-tidal Pco(2) ((ET)P(CO2)). After preparation of a cranial window and baseline recordings, the animals were subjected to experimental TBI by controlled cortical impact (CCI; 6 m/sec, 0.5 mm). Vessel lumina and intravascular cells were visualized by in vivo fluorescence microscopy (IVM) using the fluorescent dyes FITC-dextran and rhodamine 6G, respectively. Vessel diameter, cell-endothelial interactions, and thrombus formation were quantified within the traumatic penumbra by IVM up to 2 h after CCI. Arteriolar diameters increased after CCI by 26.2 +/- 2.5% (mean +/- SEM, p < 0.01 versus baseline), and remained at this level until the end of the observation period. Rolling of leukocytes on the cerebrovascular endothelium was observed both in arterioles and venules, while leukocyte-platelet aggregates were found only in venules. Microthrombi occluded up to 70% of venules and 33% of arterioles. The current data suggest that the immediate post-traumatic decrease in peri-contusional blood flow is not caused by arteriolar vasoconstriction, but by platelet activation and the subsequent formation of thrombi in the cerebral microcirculation.

MeSH terms

  • Animals
  • Arterioles / pathology
  • Arterioles / physiopathology
  • Brain / blood supply
  • Brain / physiopathology
  • Brain Injuries / complications*
  • Brain Injuries / physiopathology*
  • Cell Adhesion / physiology
  • Cerebral Arteries / pathology
  • Cerebral Arteries / physiopathology*
  • Cerebrovascular Circulation / physiology
  • Disease Models, Animal
  • Endothelial Cells / pathology
  • Fluorescent Dyes
  • Intracranial Thrombosis / etiology*
  • Intracranial Thrombosis / physiopathology*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Microcirculation / physiology*
  • Microscopy, Fluorescence
  • Platelet Activation / physiology
  • Staining and Labeling
  • Time Factors
  • Vasoconstriction / physiology


  • Fluorescent Dyes