Spreer Annette, Gerber Joachim, Baake Daniel, Hanssen Mareike, Huether Gerald, Nau Roland
Department of Neurology, University Hospital, Georg-August-University of Göttingen, Göttingen, Germany.
J Neurosci Res. 2006 Nov 15;84(7):1575-9. doi: 10.1002/jnr.21055.
Neuronal injury is frequent in bacterial meningitis, resulting in a high rate of death and neurological sequelae. In a search of potential neuroprotective strategies for treatment of bacterial meningitis, the antioxidant melatonin was neuroprotective in cell culture experiments and in a rabbit Streptococcus pneumoniae meningitis model, when treatment was started at the time of infection. In the present study, adjunctive melatonin treatment applied from the beginning of antibiotic therapy 12 hr after infection at a dose of 1.67 mg/kg/hr resulted in plasma concentrations of 451 +/- 198 ng/ml, cerebrospinal fluid (CSF) concentrations of 154 +/- 57 ng/ml and a CSF-to-plasma ratio of 0.38 +/- 0.19 (mean +/- SD). Melatonin therapy had antiinflammatory effects but did not reduce neuronal injury in either a rabbit model of gram-positive Streptococcus pneumoniae or gram-negative Escherichia coli meningitis.
神经元损伤在细菌性脑膜炎中很常见，导致高死亡率和神经后遗症。在寻找治疗细菌性脑膜炎的潜在神经保护策略时，抗氧化剂褪黑素在细胞培养实验和兔肺炎链球菌脑膜炎模型中具有神经保护作用，前提是在感染时开始治疗。在本研究中，从感染后12小时开始抗生素治疗时起，以1.67毫克/千克/小时的剂量给予辅助性褪黑素治疗，导致血浆浓度为451±198纳克/毫升，脑脊液（CSF）浓度为154±57纳克/毫升，脑脊液与血浆的比率为0.38±0.19（平均值±标准差）。褪黑素治疗具有抗炎作用，但在革兰氏阳性肺炎链球菌或革兰氏阴性大肠杆菌脑膜炎的兔模型中均未减轻神经元损伤。
