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The Korean Journal of Pathology 1998;32(2): 94-103.
Cytokine Expression on Microglial Proliferation and Apoptosis in Rat Lumbar Spinal Cord Following Unilateral Sciatic Nerve Transection.
Sang Pyo Kim, Seung Il Suh, Young Rok Cho, Seung Che Cho, Seung Pil Kim, Jong Wook Park, Jyung Sik Kwak
1Department of Pathology, Institute for Medical Science Keimyung University School of Medicine, Taegu, Korea.
2Department of Microbiology, Institute for Medical Science Keimyung University School of Medicine, Taegu, Korea.
3Department of Immunology, Institute for Medical Science Keimyung University School of Medicine, Taegu, Korea.
4Department of Forensic Medicine, Kyungpook National University School of Medicine, Taegu, Korea.
ABSTRACT
This study was carried out to elucidate the cytokine mRNAs expression and morphological features according to a microglial proliferation and apoptosis in a rat lumbar spinal cord, after a right sciatic nerve transection. The control group was composed of 5 rats (Spraque-Dawley) and the experimental group was composed of 70 rats. On post operation day (pod) 1, 2, 3, 5, and 7 eight rats were sacrificed on those days. On pod 10 five rats were sacrificed as well as five rats sacrificed on post operation weeks 2, 3, 4, 5, and 6. On light microscopy, activated microglia were often found in a perineuronal position around motoneurons in the ventral gray matter and more randomly distributed throughout the neuropil in the dorsal gray matter of lumbar spinal cord. GSA I-B4-positive microglia began to increase from 1 day after transection, and reached peak at 2~3 days and it persisted at 5~7 days and decreased thereafter. TUNEL-positive microglia was not observed in control group and began to increase from 5 days after transection and increased gradually until 3 weeks and decreased thereafter. On in situ RT-PCR, the positive signal for IL-1alpha and IL-6 mRNA was found mainly in the cytoplasm of the activated microglia and astrocytes at 1 day after transection and showed stronger signal at 3 days and decreased gradually until 10 days. TNF-alpha mRNA was detected 1 day after transection and remained for 7 days and localized to activated microglia as well as probably some astrocytes. The signal intensity of IL-1alpha and IL-6 mRNA was generally stronger than TNF-alpha mRNA. On transmission electron microscopy, there were chromatin condensation with margination toward nuclear membrane and condensation of cytoplasm at 3 days after transection. Apoptotic bodies were found after 5 days and increased gradually until 3 weeks. According to the above findings, it is concluded that apoptosis appears to be one mechanism by which activated microglia are gradually eliminated and cytokine expression seems to played an active role in the microglial turnover.
Key Words: Microglia; Cytokines; Apoptosis; Lumbar spinal cord
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