PMID- 9046307 OWN - NLM STAT- MEDLINE DCOM- 19970324 LR - 20220330 IS - 0022-3085 (Print) IS - 0022-3085 (Linking) VI - 86 IP - 3 DP - 1997 Mar TI - Delayed cytokine expression in rat brain following experimental contusion. PG - 493-504 AB - Proinflammatory cytokines mediate brain injury in experimental studies. This study was undertaken to analyze the production of proinflammatory cytokines in experimental contusion. A brain contusion causing delayed edema was mimicked experimentally in rats using a weight-drop model. Intracerebral expression of the cytokines interleukin (IL)-1 beta, tumor necrosis factor-alpha (TNF alpha), IL-6, and interferon-gamma (IFN gamma) was studied by in situ hybridization and immunohistochemistry. The animals were killed at 6 hours or 1, 2, 4, 6, 8, or 16 days postinjury. In the injured area, no messenger (m)RNA expression was seen during the first 2 days after the trauma. On Days 4 to 6 posttrauma, however, strong IL-1 beta, TNF alpha, and IL-6 mRNA expression was detected in mononuclear cells surrounding the contusion. Expression of IFN gamma was not detected. Immunohistochemical double labeling confirmed the in situ hybridization results and demonstrated that mononuclear phagocytes and astrocytes produced IL-1 beta and that mainly astrocytes produced TNF alpha. The findings showed, somewhat unexpectedly, a late peak of intracerebral cytokine production in the injured area and in the contralateral corpus callosum, allowing for both local and global effects on the brain. An unexpected difference in the cellular sources of TNF alpha and IL-1 beta was detected. The cytokine pattern differs from that seen in other central nervous system inflammatory diseases and trauma models, suggesting that the intracerebral immune response is not a uniform event. The dominance of late cytokine production indicates that many cytokine effects are late events in an experimental contusion: Different pathogenic mechanisms may thus be operative at different times after brain injury. FAU - Holmin, S AU - Holmin S AD - Department of Clinical Neuroscience, Karolinska Institute, Stockholm, Sweden. FAU - Schalling, M AU - Schalling M FAU - Hojeberg, B AU - Hojeberg B FAU - Nordqvist, A C AU - Nordqvist AC FAU - Skeftruna, A K AU - Skeftruna AK FAU - Mathiesen, T AU - Mathiesen T LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - J Neurosurg JT - Journal of neurosurgery JID - 0253357 RN - 0 (Cytokines) RN - 0 (Fluorescent Dyes) RN - 0 (Interleukin-1) RN - 0 (Interleukin-6) RN - 0 (RNA, Messenger) RN - 0 (Tumor Necrosis Factor-alpha) RN - 82115-62-6 (Interferon-gamma) RN - I223NX31W9 (Fluorescein-5-isothiocyanate) SB - IM MH - Animals MH - Astrocytes/metabolism MH - Brain/*metabolism MH - Brain Concussion/genetics/*metabolism MH - Brain Edema/genetics/metabolism MH - Corpus Callosum/metabolism MH - Cytokines/*analysis/genetics MH - Female MH - Fluorescein-5-isothiocyanate MH - Fluorescent Antibody Technique, Direct MH - Fluorescent Dyes MH - Gene Expression Regulation MH - Immunohistochemistry MH - In Situ Hybridization MH - Interferon-gamma/analysis/genetics MH - Interleukin-1/analysis/genetics MH - Interleukin-6/analysis/genetics MH - Monocytes/metabolism MH - Phagocytes/metabolism MH - RNA, Messenger/analysis/genetics MH - Rats MH - Rats, Sprague-Dawley MH - Time Factors MH - Tumor Necrosis Factor-alpha/analysis/genetics EDAT- 1997/03/01 00:00 MHDA- 1997/03/01 00:01 CRDT- 1997/03/01 00:00 PHST- 1997/03/01 00:00 [pubmed] PHST- 1997/03/01 00:01 [medline] PHST- 1997/03/01 00:00 [entrez] AID - 10.3171/jns.1997.86.3.0493 [doi] PST - ppublish SO - J Neurosurg. 1997 Mar;86(3):493-504. doi: 10.3171/jns.1997.86.3.0493.