Real-time analysis of inflammatory cytokines and regulatory gene expression in tissues surrounding the hematoma after intracerebral hemorrhage

BACKGROUND： Secondary lesions can occur in tissues surrounding the hematoma following intracerebral hemorrhage, with the presence of inflammatory reactions, cytokine expression and apoptosis These have been confirmed in animal studies. Our study sought to determine whether these could be detected in human tissues surrounding the hematoma following intracerebral hemorrhage. OBJECTIVE： To investigate expression of inflammatory cytokines, Bax and Bcl-x, and identify neural cell apoptosis in tissues surrounding the hematoma, and to analyze the correlation between them and pathological damage in intracerebral hemorrhage patients. DESIGN, TIME AND SETTING： This histopathology, controlled study was performed at the Department of Neurosurgery, Sichuan People＇s Hospital, China, from January 2003 to January 2005. PARTICIPANTS： Brain tissues 1 cm from the hematoma in 30 intracerebral hemorrhage patients served as the experimental group. Brain tissues located away from the hematoma in 7 patients served as the control group. METHODS： TUNEL was used to detect neural cell apoptosis. Immunohistochemistry （labeled dextran polymer） and RT-PCR were used to measure tumor necrosis factor- α, interleukin-1 β, interleukin-6, Bax and Bcl-x protein and mRNA expression. Pathological changes in brain tissues surrounding the hematoma were observed following HE staining. MAIN OUTCOME MEASURES： Neural cell apoptosis, inflammatory cytokines, Bax and Bcl-x protein and mRNA expression, pathological changes in brain tissues surrounding the hematoma. RESULTS： Brain tissues surrounding the hematoma were mildly damaged within 6 hours, severely damaged at 24-72 hours, and significantly improved 1 week following intracerebral hemorrhage. Expression of tumor necrosis factor- α protein and mRNA, interleukin-1β and interleukin-6 mRNA was not significant in tissues surrounding the hematoma, which was identical to the control group within 6 hours after intracerebral hemorrhage. This expression was significantly higher compared with the control group from 12-72 hours, and gradually decreased after 72 hours. The number of apoptotic neural cells reached a peak between 12- 72 hours. Tumor necrosis factor-α protein and mRNA, interleukin-1β and interleukin-6 mRNA levels were positively correlated with apoptosis, Bax protein and mRNA levels （P 〈 0.01 ）. CONCLUSION： Tumor necrosis factor-α, interleukin-1β, and interleukin-6 levels are highly correlated with apoptosis. With the decrease in tumor necrosis factor-α, interleukin-1β and interleukin-6 levels, the number of apoptotic cells gradually reduced.