Increased vulnerability of the mildly traumatized rat brain to cerebral ischemia: the use of controlled secondary ischemia as a research tool to identify common or different mechanisms contributing to mechanical and ischemic brain injury.
Fasted Wistar rats were subjected to either a mild mechanical injury, 6 min of transient forebrain ischemia, or a mild mechanical injury followed 1 h later by 6 min of forebrain ischemia. EEG and evoked potentials were assessed intermittently and morphological analyses were performed after 7 days postinjury survival. In all groups complete qualitative recovery of electrical activity and general behavior was observed with 7-day survival. However, rats subjected to combined concussion and ischemia displayed EEG spike activity and a delayed return of EEG and evoked potentials during acute recovery not evident in other groups. No overt neuronal cell loss was seen in trauma alone and was minimal or absent in ischemia alone. However, extensive bilateral CA1 and subicular pyramidal cell loss was found in the septal and mid-dorsal hippocampi in the combined trauma and ischemia group. In contrast, no overt axonal injury was found in any group. We conclude that even mild mechanical injury can potentiate selective ischemic hippocampal neuronal necrosis in the absence of overt axonal injury. This potentiation also occurs in conjunction with more generalized electrophysiological disturbances such as EEG evidence of postischemic neuronal hyperactivity suggesting that mild concussion may also decrease the threshold for post-ischemic neuronal excitation. These results suggest the potential of this model for examining common or different injury mechanisms in mechanical and ischemic brain injury.
Jenkins
L W
LW
Division of Neurosurgery, Medical College of Virginia, Richmond 23298-0693.
Moszynski
K
K
Lyeth
B G
BG
Lewelt
W
W
DeWitt
D S
DS
Allen
A
A
Dixon
C E
CE
Povlishock
J T
JT
Majewski
T J
TJ
Clifton
G L
GL
D000818:Animals; D001522:Behavior, Animal; D001794:Blood Pressure; D001921:Brain / Q000503:physiopathology*; D001930:Brain Injuries / Q000150:complications* / Q000503:physiopathology; D002470:Cell Survival; D004195:Disease Models, Animal; D004569:Electroencephalography; D005071:Evoked Potentials; D005215:Fasting; D006624:Hippocampus / Q000473:pathology; D002546:Ischemic Attack, Transient / Q000150:complications* / Q000503:physiopathology; D008297:Male; D011712:Pyramidal Tracts / Q000503:physiopathology; D051381:Rats; D011919:Rats, Inbred Strains; D012016:Reference Values