Pfister H W, Koedel U, Lorenzl S, Tomasz A
Department of Neurology, University of Munich, FRG.
Stroke. 1992 Dec;23(12):1798-804. doi: 10.1161/01.str.23.12.1798.
We tested in a rat meningitis model 1) whether pneumococcal cell wall components are capable of producing changes in regional cerebral blood flow, brain water content, and intracranial pressure similar to those we have already observed after intracisternal inoculation of live pneumococci and 2) whether antioxidants would modulate these alterations in the early phase of meningitis.
Regional cerebral blood flow as measured by laser Doppler flowmetry and intracranial pressure were monitored continuously for 4 hours after intracisternal challenge. Brain edema formation was assessed by brain water content determinations. We investigated the following groups: rats challenged intracisternally with the whole intact pneumococcal cell wall (n = 7) or the pneumococcal cell wall hydrolyzed by the M1-muramidase (n = 7); rats injected intracisternally with phosphate-buffered saline (n = 6); rats pretreated intravenously with superoxide dismutase conjugated with polyethylene glycol (10,000 units/kg) and injected intracisternally with cell wall components (n = 5) or phosphate-buffered saline (n = 6); rats injected intracisternally with phosphate-buffered saline and pretreated intravenously with polyethylene glycol (10% solution, 1.2 ml/kg, n = 5) or continuously treated with intravenous free superoxide dismutase (22,000 units/kg per hour, n = 6); and rats continuously treated intravenously with deferoxamine mesylate (10 mg/kg per hour) and injected intracisternally with cell wall components (n = 6) or phosphate-buffered saline (n = 7).
Both pneumococcal cell wall preparations produced a significant increase in regional cerebral blood flow, intracranial pressure, and brain water content. Conjugated superoxide dismutase as well as deferoxamine prevented the increase in intracranial pressure and brain water content. In addition, the increase in regional cerebral blood flow as observed in untreated, cell wall-challenged rats (baseline, 100%; 183.1 +/- 12.3% after 4 hours, mean +/- SEM) was significantly attenuated by administration of both conjugated superoxide dismutase (136.6 +/- 14.1%) and deferoxamine (149.8 +/- 8.2%) (p < 0.05). Polyethylene glycol-conjugated superoxide dismutase alone produced an increase in regional cerebral blood flow (125.6 +/- 8.7% after 4 hours). We found that polyethylene glycol per se accounts for this action.
These data show that pneumococcal cell wall components containing teichoic acid produce changes in regional cerebral blood flow, intracranial pressure, and brain water content and that oxygen radicals contribute to these pathophysiological alterations in the early phase of experimental pneumococcal meningitis.
我们在大鼠脑膜炎模型中进行了测试，1）肺炎球菌细胞壁成分是否能够引起局部脑血流量、脑含水量及颅内压的变化，这些变化是否与我们在脑池内接种活肺炎球菌后所观察到的相似；2）抗氧化剂是否会在脑膜炎早期阶段调节这些改变。
脑池内激发后，通过激光多普勒血流仪测量局部脑血流量，并连续监测颅内压4小时。通过测定脑含水量评估脑水肿形成情况。我们研究了以下几组：脑池内接种完整的肺炎球菌细胞壁（n = 7）或经M1-溶菌酶水解的肺炎球菌细胞壁（n = 7）的大鼠；脑池内注射磷酸盐缓冲盐水的大鼠（n = 6）；静脉注射聚乙二醇偶联的超氧化物歧化酶（10,000单位/千克）预处理后，脑池内注射细胞壁成分（n = 5）或磷酸盐缓冲盐水的大鼠（n = 6）；脑池内注射磷酸盐缓冲盐水且静脉注射聚乙二醇（10%溶液，1.2毫升/千克，n = 5）预处理或静脉持续注射游离超氧化物歧化酶（22,000单位/千克·小时，n = 6）的大鼠；静脉持续注射甲磺酸去铁胺（10毫克/千克·小时）且脑池内注射细胞壁成分（n = 6）或磷酸盐缓冲盐水的大鼠（n = 7）。
两种肺炎球菌细胞壁制剂均使局部脑血流量、颅内压和脑含水量显著增加。偶联的超氧化物歧化酶以及去铁胺可防止颅内压和脑含水量升高。此外，在未治疗、接受细胞壁激发的大鼠中观察到的局部脑血流量增加（基线为100%；4小时后为183.1±12.3%，均值±标准误），通过给予偶联的超氧化物歧化酶（136.6±14.1%）和去铁胺（149.8±8.2%）均得到显著减弱（p < 0.05）。单独的聚乙二醇偶联超氧化物歧化酶使局部脑血流量增加（4小时后为125.6±8.7%）。我们发现这一作用是由聚乙二醇本身引起的。
这些数据表明，含有磷壁酸的肺炎球菌细胞壁成分可引起局部脑血流量、颅内压和脑含水量的变化，并且氧自由基在实验性肺炎球菌脑膜炎早期阶段促成了这些病理生理改变。
