A mouse model for evaluation of capillary perfusion, microvascular permeability, cortical blood flow, and cortical...

Genetically engineered mice have successfully been used to investigate molecular and cellular mechanisms associated with cell dysfunction following brain trauma. Such animals may also offer a possibility to investigate mechanisms involved in posttraumatic hemodynamic alterations. The objective of the study was to establish a mouse model in which important hemodynamic alterations following trauma could be analyzed. C57/BL6 male mice were subjected to controlled cortical impact injury (CCI) or sham-injury. Distribution of blood flow was estimated by determining number of perfused capillaries using FITC-dextran as an intravascular marker. Cortical blood flow was measured using [(14)C]-iodoantipyrine, brain water content (BWC) was measured using a wet vs. dry weight method, and permeability surface area product (PS) was estimated by the transfer constant for [(51)Cr]-EDTA. Number of perfused capillaries in the contusion area was progressively reduced during the first 24 h following trauma by at most 60% relative to a value of 329 +/- 61/mm(2) in sham-injured animals. Blood flow in the contusion area decreased simultaneously by at most 50% relative to a control value of 1.8 +/- 0.4 mL.min(-1).g(-1), and was reduced further in subregions within the contusion area. BWC in the injured hemisphere increased from 79.3 +/- 0.5% at control to at most 79.9 +/- 0.6% at 24 h post trauma. PS in the injured hemisphere increased by 71% at 3 h post trauma relative to a control value of 0.45 +/- 0.1 microL.min(-1).g(-1), and was close to control at 24 h. The present study demonstrates that brain trauma in addition to a reduction in cortical blood flow, reduces number of perfused capillaries, which most likely affects exchange of nutrients and fluid. The CCI in mouse is likely to be a useful tool to elucidate mechanisms involved in hemodynamic alterations following brain trauma.