Dezengrini R, Weiss M, Torres F D, Oliveira M S, Furian F, Mello C F, Weiblen R, Flores E F
Setor de Virologia, Departamento de Medicina Veterinaria Preventiva, Universidade Federal de Santa Maria (UFSM), Santa Maria, Brazil.
J Neurovirol. 2009 Apr;15(2):153-63. doi: 10.1080/13550280802578067.
We herein report an investigation of nitric oxide (NO) levels, a candidate molecule for neuronal toxicity and dysfunction, in the brain of rabbits during experimental neurological infection by bovine herpesvirus 5 (BoHV-5). Spectrophotometry for NO products (NO(2) and NO(3)) revealed that NO levels were significantly increased (F(4, 40) = 3.33; P <.02) in several regions of the brain of rabbits with neurological disease, correlating with moderate to high BoHV-5 titers. Immunohistochemistry of brain regions revealed a group of cells with neuronal and astrocyte morphology expressing the enzyme inducible NO synthase (iNOS) close to virus antigen-positive neurons. In addition, the investigation of nitric oxide levels between 2 and 6 days post infection (d.p.i.) revealed an initial increase in NO levels in the olfactory bulb and cortex (OB/OC) and anterior cortex (AC) at day 3 p.i., correlating with the initial detection of virus. As the infection proceeded, increased NO levels-and infectivity-were progressively being detected in the OB/CO and AC at day 4 p.i. (F(12, 128) = 2.82; P <.003); at day 5 p.i. in several brain regions (P <.003 in the OB/OC); and at day 6 p.i. in all regions (P <.003) but the thalamus. These results show that BoHV-5 replication in the brain of rabbits induces an overproduction of NO. The increase in NO levels in early infection correlated spatially and temporally with virus dissemination within the brain and preceded the development of neurological signs. Thus, the overproduction of NO in the brain of BoHV-5-infected rabbits may be a component of the pathogenesis of BoHV-5-induced neurological disease.
我们在此报告了一项关于一氧化氮（NO）水平的研究，NO是一种可能导致神经元毒性和功能障碍的分子，研究对象为实验性神经感染牛疱疹病毒5型（BoHV-5）的家兔大脑。对NO产物（NO₂和NO₃）的分光光度测定显示，患有神经疾病的家兔大脑的几个区域中，NO水平显著升高（F(4, 40) = 3.33；P <.02），这与中等至高的BoHV-5滴度相关。对脑区的免疫组织化学分析显示，一组具有神经元和星形胶质细胞形态的细胞表达诱导型一氧化氮合酶（iNOS），且靠近病毒抗原阳性神经元。此外，对感染后2至6天（d.p.i.）的一氧化氮水平进行的研究显示，感染后第3天，嗅球和皮质（OB/OC）以及前皮质（AC）中的NO水平最初升高，这与病毒的首次检测相关。随着感染的进展，在感染后第4天，OB/CO和AC中逐渐检测到NO水平升高以及传染性增加（F(12, 128) = 2.82；P <.003）；感染后第5天，几个脑区出现这种情况（OB/OC中P <.003）；感染后第6天，除丘脑外的所有区域均出现这种情况（P <.003）。这些结果表明，BoHV-5在家兔大脑中的复制会诱导NO的过量产生。早期感染中NO水平的升高在空间和时间上与病毒在脑内的传播相关，且早于神经症状的出现。因此，BoHV-5感染家兔大脑中NO的过量产生可能是BoHV-5诱导的神经疾病发病机制的一个组成部分。
