Thoracic shock wave injury causes behavioral abnormalities in mice.
BACKGROUND
Mild traumatic brain injury (mTBI) is caused by complex mechanisms of systemic, local and cerebral responses to blast exposure. However, the molecular mechanisms of cognitive impairment after exposure to blast waves are not clearly known. We tested the hypothesis that thoracic injury induced functional and morphological impairment in the brain, leading to behavioral abnormalities.


METHODS
Mice were exposed to laser-induced shock waves (LISWs) impacting the thorax and assessed for behavioral outcome at 7 and 28 days post injury. Hippocampus and lung were collected for histopathological analysis and gene expression profiling after injury.


RESULTS
Thoracic injury transiently decreased the heart rate, blood pressure, peripheral oxyhemoglobin saturation and cerebral blood flow immediately after LISW exposure. Although LISWs exposure caused pulmonary contusions, hemorrhage was not apparent in the brain. At 7 and 28 days after, the injured mice exhibited impaired short-term memory and depression-like behavior compared with controls. Histological assessments showed an increase in neuronal cell death after shock wave exposure, especially in the CA3 region of the hippocampus. Moreover, shock wave exposure altered the expression of functionally relevant genes in the hippocampus at 1 h and 1 day post injury.


CONCLUSIONS
Our findings indicate that the LISW-induced thoracic injury with no direct impact on the brain affected the hippocampal gene expression and led to morphological alterations, resulting in behavioral abnormalities. Therefore, body protection may be extremely important in the effective prevention against blast-induced alterations in brain function.
Division of Traumatology, Research Institute, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama, 359-8513, Japan. hiromyzk@ndmc.ac.jp.
Hiromi
H
Miyazaki
Department of Traumatology and Critical Care Medicine, National Defense Medical College Hospital, 3-2 Namiki, Tokorozawa, Saitama, 359-8513, Japan.
Hiroki
H
Miyawaki
Department of Anesthesiology, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama, 359-8513, Japan.
Yasushi
Y
Satoh
Division of Traumatology, Research Institute, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama, 359-8513, Japan.
Takami
T
Saiki
Division of Biomedical Information Sciences, Research Institute, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama, 359-8513, Japan.
Satoko
S
Kawauchi
Division of Biomedical Information Sciences, Research Institute, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama, 359-8513, Japan.
Shunichi
S
Sato
Division of Traumatology, Research Institute, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama, 359-8513, Japan.
Daizoh
D
Saitoh
D000818:Animals; D001522:Behavior, Animal; D001753:Blast Injuries / Q000150:complications* / Q000473:pathology / Q000503:physiopathology; D056654:CA3 Region, Hippocampal / Q000473:pathology*; D016923:Cell Death; D002560:Cerebrovascular Circulation; D003072:Cognition Disorders / Q000209:etiology* / Q000473:pathology; D003863:Depression / Q000209:etiology / Q000473:pathology / Q000523:psychology*; D006624:Hippocampus / Q000378:metabolism* / Q000473:pathology; D020287:In Situ Nick-End Labeling; D007834:Lasers; D008297:Male; D008570:Memory, Short-Term; D051379:Mice; D009474:Neurons / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D013898:Thoracic Injuries / Q000150:complications / Q000473:pathology / Q000523:psychology*; D059467:Transcriptome
D012333:RNA, Messenger
Cognitive dysfunction; Hippocampus; Shock waves; Thoracic injury