Distinct Time Courses of Secondary Brain Damage in the Hippocampus Following Brain Concussion and Contusion in Rats

Distinct Time Courses of Secondary Brain Damage in the Hippocampus Following Brain Concussion and Contusion in Rats

YUKO NAKAJIMA,¹ YUTAKA HORIUCHI,¹ HIROSHI KAMATA,¹ MASAYOSHI YUKAWA,¹ MASATO KUWABARA¹ and TAKASHI TSUBOKAWA²

¹Department of Veterinary Medicine, Nihon University College of Bioresonance Bioresource Science, Kanagawa, Japan
²Department of Neurosurgery, Nihon University School of Medicine, Tokyo, Japan

Secondary brain damage (SBD) is caused by apoptosis after traumatic brain injury that is classified into concussion and contusion. Brain concussion is temporary unconsciousness or confusion caused by a blow on the head without pathological changes, and contusion is a brain injury with hemorrhage and broad extravasations. In this study, we investigated the time-dependent changes of apoptosis in hippocampus after brain concussion and contusion using rat models. We generated the concussion by dropping a plumb on the dura from a height of 3.5 cm and the contusion by cauterizing the cerebral cortex. SBD was evaluated in the hippocampus by histopathological analyses and measuring caspase-3 activity that induces apoptotic neuronal cell death. The frequency of abnormal neuronal cells with vacuolation or nuclear condensation, or those with DNA fragmentation was remarkably increased at 1 hr after concussion (about 30% for each abnormality) from the pre-injury level (0%) and reached the highest level (about 50% for each) by 48 hrs, whereas the frequency of abnormal neuronal cells was increased at 1 hr after contusion (about 10%) and reached the highest level (about 40%) by 48 hrs. In parallel, caspase-3 activity was increased sevenfold in the hippocampus at 1 hr after concussion and returned to the pre-injury level by 48 hrs, whereas after contusion, caspase-3 activity was continuously increased to the highest level at 48 hrs (fivefold). Thus, anti-apoptotic-cell-death treatment to prevent SBD must be performed by 1 hr after concussion and at latest by 48 hrs after contusion.

keywords —— secondary brain damage; apoptosis; brain concussion; brain contusion; rat

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Tohoku J. Exp. Med., 2010, 221, 229-235

Correspondence: Yuko Nakajima, Department of Veterinary Medicine Nihon University College of Bioresonance Bioresource Sciences, 1866 Kameino, Fujisawa, 252-8510 Kanagawa, Japan.

e-mail: y09064823383@yahoo.co.jp