Haberl R L, Anneser F, Ködel U, Pfister H W
Department of Neurology, University of Munich, Germany.
Neurol Res. 1994 Apr;16(2):108-12. doi: 10.1080/01616412.1994.11740205.
Nitric oxide (NO) is a mediator of haemodynamic changes and cytotoxicity in in vivo models of inflammation such as endotoxaemic shock. The purpose of this study was to investigate whether NO may be involved in the increase of cerebral blood flow (CBF), intracranial pressure (ICP) and brain water content, known to occur in the early phase of pneumococcal meningitis. Rats injected intracisternally with live pneumococci were either untreated or received 5 mg kg-1 i.v. NG-nitro-L-arginine methyl ester (L-NAME), an inhibitor of NO synthase. Pretreatment with L-NAME prevented the increase in CBF, ICP and brain water content, as seen in untreated animals. CBF tended to return towards baseline when rats were treated with L-NAME 2 h after pneumococcal injection. Whereas none of the untreated and L-NAME-pretreated animals died during the 6 h observation period, 3 out of 9 rats treated with L-NAME and 7 out of 9 rats with simultaneous i.v. injection of L-NAME and L-arginine died. Our results provide preliminary evidence that NO may be involved as a mediator of CBF changes and oedema formation in the early phase of pneumococcal meningitis in the rat. NO inhibition, however, may have detrimental effects of still unidentified cause, as indicated by the increased mortality in treated animals. Further studies with analysis of the causes of mortality, structurally different NO synthase inhibitors and direct evaluation of NO synthase induction are needed to further support this hypothesis.
一氧化氮（NO）是诸如内毒素血症休克等体内炎症模型中血流动力学变化和细胞毒性的介质。本研究的目的是调查NO是否可能参与了已知在肺炎球菌性脑膜炎早期出现的脑血流量（CBF）增加、颅内压（ICP）升高和脑含水量增加。向大鼠脑池内注射活的肺炎球菌后，一部分大鼠不做处理，另一部分大鼠静脉注射5 mg kg-1的NG-硝基-L-精氨酸甲酯（L-NAME），一种一氧化氮合酶抑制剂。如在未处理动物中所见，L-NAME预处理可防止CBF、ICP和脑含水量增加。当在注射肺炎球菌后2小时用L-NAME处理大鼠时，CBF倾向于恢复到基线水平。在6小时的观察期内，未处理和L-NAME预处理的动物均未死亡，但9只接受L-NAME处理的大鼠中有3只死亡，9只同时静脉注射L-NAME和L-精氨酸的大鼠中有7只死亡。我们的结果提供了初步证据，表明NO可能作为大鼠肺炎球菌性脑膜炎早期CBF变化和水肿形成的介质发挥作用。然而，如处理组动物死亡率增加所示，抑制NO可能有尚未明确的有害影响。需要进一步研究分析死亡原因、结构不同的一氧化氮合酶抑制剂以及直接评估一氧化氮合酶的诱导情况，以进一步支持这一假设。
