Lackner Peter, Part Andrea, Burger Christoph, Dietmann Anelia, Broessner Gregor, Helbok Raimund, Reindl Markus, Schmutzhard Erich, Beer Ronny
Department of Neurology, Innsbruck Medical University, Innsbruck, Austria.
Malar J. 2009 Feb 27;8:36. doi: 10.1186/1475-2875-8-36.
Cerebral malaria (CM) is associated with high mortality and morbidity caused by a high rate of transient or persistent neurological sequelae. Studies on immunomodulatory and neuroprotective drugs as ancillary treatment in murine CM indicate promising potential. The current study was conducted to evaluate the efficacy of glatiramer acetate (GA), an immunomodulatory drug approved for the treatment of relapsing remitting multiple sclerosis, in preventing the death of C57Bl/6J mice infected with Plasmodium berghei ANKA.
GA treatment led to a statistically significant lower risk for developing CM (57.7% versus 84.6%) in treated animals. The drug had no effect on the course of parasitaemia. The mechanism of action seems to be an immunomodulatory effect since lower IFN-gamma levels were observed in treated animals in the early course of the disease (day 4 post-infection) which also led to a lower number of brain sequestered leukocytes in treated animals. No direct neuro-protective effect such as an inhibition of apoptosis or reduction of micro-bleedings in the brain was found.
These findings support the important role of the host immune response in the pathophysiology of murine CM and might lead to the development of new adjunctive treatment strategies.
脑型疟疾（CM）与因高比率的短暂性或持续性神经后遗症所致的高死亡率和高发病率相关。关于免疫调节和神经保护药物作为鼠类CM辅助治疗的研究显示出有前景的潜力。当前研究旨在评估醋酸格拉替雷（GA），一种已被批准用于治疗复发缓解型多发性硬化症的免疫调节药物，在预防感染伯氏疟原虫ANKA的C57Bl/6J小鼠死亡方面的疗效。
GA治疗使治疗组动物发生CM的风险在统计学上显著降低（57.7%对84.6%）。该药物对寄生虫血症进程无影响。作用机制似乎是一种免疫调节作用，因为在疾病早期（感染后第4天）治疗组动物中观察到较低的γ干扰素水平，这也导致治疗组动物脑内滞留白细胞数量减少。未发现诸如抑制凋亡或减少脑内微出血等直接的神经保护作用。
这些发现支持宿主免疫反应在鼠类CM病理生理学中的重要作用，并可能导致新的辅助治疗策略的开发。
