| Intracerebral hemorrhage (ICH) is one of the frequently-occurring diseases of the nervous system, which is acute and severe, its mortality is very high. Thrombin forms from hemorrhage, hemoglobin which is produced by lysed erythrocytes after cerebral hemorrhage are two kinds of neuroeoxicity medium, and they contributed to brain edema by leading to a series of pathological changes, such as injuring the nerve cells, damaging the integrity of blood brain barrier, inducing pro-oxidative activity and apoptosis mechanism in the perihematoma and so on. Hemorrhagic stroke is frequently accompanied by intensive inflammation, including an initial infiltration by neutrophils followed by macrophage accumulation. Experimental and clinical researches have confirmed that cerebral hemorrhages can induce a rapid production of proinflammatory cytokines, including tumor necrosis factor-a (TNF-a) , in brain parenchyma and cerebrospinal fluid. Lots of the allergic toxin such as C3a and C5a were produced after the complements were activated by ICH, which stimulate the synthesis of TNF-a ininflammatory cells, activate cells to produce cytokines, neurotrophy factor and acute-phase protein, while increasing adhesion molecules expression. Other cytokines such as leukotriene C4(LTC4)> interleukin-6 (IL-6) ^ interferon- Y (IFN- Y), oxygen free radical and so on also play a very important role during the development of brain edema. The purpose of this study was to investigate whether ICH induces production of proinflammatory cytokines( such as TNF-ou IL-6n IL-1P) inside the cavity of hematoma after micro-injury treatment and to evaluate the kinetics of their release in relation to the size of the brain lesion and the clinical course of the disease by an enzyme-linked immunosorbent assay. The study may offer theoretic supports for the consequence of brain damage after ICH. Materials and methodsWe studied 60 patients (38 men, 22women, mean age, 58.25±13.29 years) with hypertensive cerebral hemorrhage (within 2~4 hours after onset) who were admitted at the Emergency Medical Center of Kaifeng second people's hospital from October 2002 to September 2004. All patients with supratentorial, intraparenchymal cerebral hemorrhage were evaluated by CT or MRI. We excluded patients with (1) pregnancy; (2) history of recent (within 2 weeks before admission) infection; (3) concurrent major cardiac, renal, hepatic, autoimmune, and cancerous diseases or diabetes; (4) history of previous stroke or head trauma; (5) obvious signs of acquired infection after admission; (6) taking immunosuppressive or anti-inflammatory drugs. Volume of the ICH in milliliters was estimated on the basis of approximate ellipse volume with the tcxAxBxC/6 formula, where A represents the largest diameter of the hematoma on axial CT cuts in centimeters, B the diameter of hematoma perpendicular to A on the same cut, and C the number of CT slices in which hematoma is visible multiplied by the slice thickness in centimeters. Accordingto the volume of hemorrhage, these patients were classified as Low volume group (Group I, ^40ml), Medium volume group (Group II, 41 ~70 ml), High volume group (Group III, ^7 lml) matched for age , sex and the history of hypertension. According CT scan results all patients were treated by microtraumatic operation with YL-1 modle needle set (single used, 3mm diameter) under local anesthesia beside bed. We should ensure the site of puncture, the position and the range of hemorrhage before operation. After putting the needle into the center of hemorrhage, we were keeping the needle in the cavity of hemorrhage, drawing out the liquid of hemorrhage by the side hole. Then we were putting the needle of comminution into the cavity, washing the cavity again and again with 10 milliliters of low temperature fluid (physiological saline with heparin). 20000 IU of Urokinase was injected through the catheter to facilitate aspiration every time, and the catheter was clamped and drained after 3hs. The hematoma fluid was serially drawn through the needle at five times: 6hs (as soon as the patient was operated), 24, 48, 72 and 120hs after onset. Samples were immediately centrifuged (1500g, 10 minutes), and the liquid of upper level were stored at-20°C until used. Sample levels of TNF-a, IL-6 and IL-ip were measured with quantitative "sandwich" enzyme-linked immunosorbent assay (Quantikine) kits. CT scan was repeated to monitor the change of hematoma and observe the effect after operation. While medical therapy was administered under current guidelines, including control of intracranial pressure, maintenance of normotension (per patient's premorbid range of blood pressure control), physical therapy, intravenous fluids, H2 blockers, maintenance of normoglycemia, antibacterial and early nutritional support. Results1. Change of TNF-a in hematoma fluid after hypertensive cerebral hemorrhage: TNF-a was found in hematoma fluid in three groups after ICH 6 hours. And the difference invalue among three groups was not statistically significant at 6 hours (P>0.05). The levels of TNF-a were increased gradually at different ratio after 6hours until they got peaks, and TNF-a reached a peak at 48 hours post hemorrhage in three groups. They were decreased gradually after that time. We found that the TNF-a elevated levels were significantly positive correlated to the volume of the hemorrhage measured at 24 hours and later time points. The volume of hematoma was more big, and the level of TNF-a went up more high in the cavity. The levels of TNF-a were significant lower in Group I compared with GroupII and III(P<0.001), and like lower in GroupII compared with GroupIII(/>< 0.001 or<0.01) at 24,48,72,120hs.2. Change of IL- 6 in hematoma fluid after hypertensive cerebral hemorrhage: IL-6 was found in hematoma fluid in three groups after ICH 6 hours. And the difference in value among ICH groups was not statistically significant at 6 hours (P>0.05). The levels of IL-6 were increased gradually at different ratio after 6 hours until they got peaks, and we found that the levels of IL-6 were elevated in the patients in three groups that peaked within 72 hours. They reduced gradually after that time. We found that the IL-6 elevated levels were significantly correlated to the volume of the hemorrhage measured at 24 hours and later time points. The volume of ICH was more big, the IL-6 level went up more high. The levels of IL-6 were significant lower in Group I compared with Group II and III(P< 0.001), and like lower in Group II compared with GroupIII(P<0.05 or<0.01) at 24, 48, 72,120hs.3. Change of IL-ip in hematoma fluid after hypertensive cerebral hemorrhage: IL-ip was found in the liquid of hematoma all patients in three groups after ICH 6 hours. The IL-ip level was the lowest in patients in Group I, the difference in value among Group I and Group III was statistically significant at 6 hours (P<0.05). The levels of IL-lp wereincreased gradually at different ratio after 6 hours until they got peaks, and we found that the levels of IL-ip were elevated in three groups that peaked at 72 hours. They reduced gradually after that time. We found that the IL-ip elevated levels were significantly correlated to the volume of the hemorrhage measured at 24 hours and later time points. The bigger hemorrhage volumes, the higher the IL-ip levels went up in the cavity. The levels of IL-ip were significant lower in Group I compared with GroupIII(P< 0.001), and like lower in Group II compared with GroupIII(P<0.05 or<0.001), and similar lower in Group I compared with Group II (P<0.05, <0.01 or<0.001) at 24,48, 72,120hs. 4. The total effective rate was significantly higher in Group I after micro-injury operation treatment compare with Group 11(90.8% vs 57.1%, P<0.05) and Group 111(90.8% vs 27.8%, P<0.005). Although the total effective rate in Group II was higher than that in Group III, the difference in value among Group II and Group III was not statistically significant (57.1% vs 27.8%,P>0.05). The mortality in Group III was significantly higher than that in Group II (61.1% vs 23.8%, P<0.05)and Group I (61.1% vs 4.8%, P< 0.005). Conclusions1. The inflammatory cytokines was involved in the pathological process of cerebral hemorrhage. TNF-cuIL-6 and IL-ip were observed in hematoma fluid at 6hours after ICH. The levels of TNF-a, IL-6 and IL-ip were increased gradually at different ratio after 6 hours until they got peaks at different time.2. TNF-ou IL-6 and IL-ip were positive correlated to the volume of hematoma. The hemorrhage volume was more big, the levels of inflammatory cytokines contain to measured more high. The levels of proinflammatory molecules in the course of intracerebral hemorrhage onset were associated with the outcome of ICH. The higherinflammatory cytokines levels, the more intensive inflammatory and the worse neurologic outcome.3. The study may offer some theoretic supports for the treatment and ulterior study of ICH.4. We thought that micro-injury operation with YL-1 modle needle sets under local anesthesia beside bed and aspiration, thrombolysis with urokinase and heparin is one of safe, simple and effective way in reduction of ICH volume. |
PDF Full Text Request