Astrocytic response, profiles of aquaporin 4 and matrix metalloproteinase contribution to the process of brain edema formation in the fat embolism and focal brain ischemia model in rat

2004 Fiscal Year Final Research Report Summary

• Project/Area Number: 15591635
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Anesthesiology/Resuscitation studies
• Research Institution: Yamaguchi University
• Principal Investigator: ISHIDA Kazuyoshi Yamaguchi Univ., School of Medicine, Research Associate, 医学部, 助手 (80314813)
• Co-Investigator(Kenkyū-buntansha): SAKABE Takefumi Yamaguchi Univ., School of Medicine, Professor, 医学部, 教授 (40035225) ; FUKUDA Shirou Yamaguchi Univ., Hospital, Research Associate, 医学部附属病院, 助手 (70322245)
• Project Period (FY): 2003 – 2004
• Keywords: fat embolism / brain edema / astrocyte / aquaporin / basal lamina / triolein / GFAP / matrix metalloproteinase

Research Abstract

We examined the astrocytic response and aquaporin (AQP)4 profiles in the process of brain edema formation in the fat embolism model in rat, comparing to those in focal brain ischemia.
Brain water content increased 2 to 72 h after intracarotid injection of triolein with no difference among the three evaluation time points. Histological evaluation exhibited the disappearance of the details of nucleus, and Nissl bodies and pyknosis of nuclei. Vacuole degeneration in cytoplasm and halo formation around neurons and small vessels was observed. Reactivity of astrocyte was also increased in peri-affected lesion 2 to 72 h after injection and was strong with hypertrophy and mitosis in the 72h after triolein injection. AQP4 immunostaining was markedly increased in pen-affected lesion but was absent in the core of the lesion 2 to 72 h after injection. Two hour after MCAO, only pyknosis of nuclei, and Nissl bodies disappearance were observed. Although astrocyte reactivity was seen in the peri-affected lesion, there was no significant increase of brain water content or changes in AQP4 immunostaining. Immunostaining of basal lamina is tended to be lower in the triolein groups than the MCAO group.
The present study showed that fat embolism with triolein produces severe brain edema with AQP4 and basal lamina modulation at early stage after the insult in a quite contrast with MCAO after 2 h without significant increase in water content and AQP4 changes.
However astrocytes reactivity became strong with hypertrophy and mitosis in the 72h after triolein injection with accordance with the previous MCAO report. Early therapy would be needed to prevent brain damage as well as edema formation in fat embolism cases and AQP4 channel and matrix metalloproteinase modulation would lead the new therapeutic strategy.