Establishment of a stable mouse model of brain death by the method of the gradually increasing intracranial pressure.
OBJECTIVE
To establish a stable and modified mouse model of brain death (BD) and to share our experiences in BD induction and maintenance.


METHODS
Totally 35 C57BL/6 male mice were randomized into BD group (n=25) or sham control group (n=10). BD was induced by inserting a 2F Fogarty catheter connected to a syringe pump after trepanation of the left frontoparietal area and injecting volume at the speed of 6 μl/min until spontaneous respiration ceased. BD was diagnosed by electroencephalogram, apnea testing,as well as testing of brain stem reflexes. Mechanical ventilation was performed by orotracheal intubation. Right carotid artery was intubated by a PE-10 cannula for the continuous monitoring of mean blood pressure (MAP) and heart rate (HR). The right external jugular vein was catheterized for volume resuscitation.The sham control group underwent the same procedure with catheter insertion but without balloon inflation.Livers were removed and fixed in paraffin to evaluate the histological alterations with the light microscopy.


RESULTS
Mouse models of BD were successfully established about 20 minutes after balloon inflation, and the mean balloon volume at the time of BD was (105.77 ± 21.57)μl. The MAP and HR rapidly increased on occurrence of BD and the peak value was (128.28 ± 17.16) mmHg and (434.16 ± 55.75) beat/min, respectively, which were significant higher than those in the sham control group at the same time point (P=0.000). During the 4-hour follow-up time, MAP and HR in 72% (18/25) of BD animals remained haemodynamically stable. No animal died due to anesthesia and surgical operation.Hepatic tissues in BD mice showed mild focal ischemic damages (cellular edema, congestion, and inflammatory infiltration), which were slighter and fewer in sham control group.


CONCLUSIONS
The mouse model of BD was successfully established with lower surgical difficulty and can be performed in a standardized, reproducible and successful way.
Department of Hepatobiliary Surgery & Hepatobiliary Surgical Institute, Chinese PLA General Hospital, Beijing 100853, China.
Yong
Y
Shi
Department of Hepatobiliary Surgery & Hepatobiliary Surgical Institute, Chinese PLA General Hospital, Beijing 100853, China.
Chong-hui
CH
Li
Department of Hepatobiliary Surgery & Hepatobiliary Surgical Institute, Chinese PLA General Hospital, Beijing 100853, China.
Nian-jun
NJ
Xiao
Department of Hepatobiliary Surgery & Hepatobiliary Surgical Institute, Chinese PLA General Hospital, Beijing 100853, China.
Wen-jie
WJ
Li
Department of Hepatobiliary Surgery & Hepatobiliary Surgical Institute, Chinese PLA General Hospital, Beijing 100853, China.
Yu-rong
YR
Liang
Department of Hepatobiliary Surgery & Hepatobiliary Surgical Institute, Chinese PLA General Hospital, Beijing 100853, China.
Ke
K
Pan
Department of Hepatobiliary Surgery & Hepatobiliary Surgical Institute, Chinese PLA General Hospital, Beijing 100853, China.
Xin-lan
XL
Ge
D000818:Animals; D001926:Brain Death; D004195:Disease Models, Animal; D006339:Heart Rate; D007427:Intracranial Pressure; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL