The Effect of Immediate Hemodynamic Change on Memory Dysfunction and Histopathological Change in the CA1 Sector of the Hippocampus in Diffuse Brain Injury of the Rat

Lim, Dong Jun; Park, Youn Kwan; Kim, Ae Ree; Chung, Heung Seob; Lee, Ki Chan; Lee, Hoon Kap

Abstract

Secondary brain insults such as cerebral compression, hypoxia, and ischemia materially influence the outcome of human traumatic brain injury(TBI). Memory dysfunction following such injury is a common clinical observation, but the pathologic substrate underlying this loss of function has not been well-characterized. In the present study, we examined the effects of immediate hemodynamic change resulting from moderate closed head injury on memory dysfunction, neuronal cell loss and synaptic loss in the CA1 sector of the hippocampus. A modified Morris Water Maze(MWM) memory paradigm was used to assess memory retention in rats for five consecutive days before and for two days after injury. A total of 24 Sprague-Dawley rats, regardless of sex, weighing 250-330gm, were used, and were divided into four groups : sham control, head injury-no treatment(group 1), head injury-hypotension(group 2), and head injury-resuscitation(group 3). After injury, latency time to invisible platform in spatial navigation was longer in the head injury-hypotension group(group 2) than in the other injury groups(p<0.05). At the completion of cognitive testing, the animals were sacrificed and neuronal cell loss and synaptic loss in the hippocampal CA1 sector were examined with H and E staining and immunohistochemical staining to synaptophysin. The number of pyramidal neurons in the hippocampal CA1 sector per 5000nm2 was lower in the injury groups(20.3+/-3.0 in group 1, 20.2+/-3.4 in group 2, 19.8+/-2.1 in group 3, mean+/-standard deviation) than in the sham control group(23.7+/-3.5). The density of immunohistochemical staining to synaptophysin tended to be less in groups 1 and 2 than in the sham control group, and tended to increase to the level of the sham control group in group 3. The present study showed that during a period of acute TBI, neuronal and/or synaptic loss in the hippocampal CA1 sector may be responsible for transient memory disturbance and that to prevent neurologic deficit after TBI, active therapy or stabilization of the hemodynamic state is important.