Cornblath David R, Hoke Ahmet
School of Medicine, Johns Hopkins University, Baltimore, Maryland, USA.
Curr Opin Neurol. 2006 Oct;19(5):446-50. doi: 10.1097/01.wco.0000245366.59446.57.
To describe recent advances in HIV neuropathy.
Epidemiologic studies since highly active antiretroviral therapy was introduced have shown that the incidence of HIV-associated distal sensory polyneuropathy is reduced. Studies have also shown the relationship between distal sensory polyneuropathy and the use of neurotoxic antiretroviral drugs. Skin punch biopsy for assessment of epidermal nerve fiber density is valuable both for diagnosis of distal sensory polyneuropathy and as a predictor of the condition occurring in the future. An in-vitro model of antiretroviral toxic neuropathy showed that dideoxynucleoside analogues that cause neuropathy exert direct mitochondrial toxicity that is not mediated indirectly through the inhibition of DNA polymerase-gamma. HIV envelope protein gp120 exerts axonal toxicity directly or indirectly via perineuronal Schwann cells. A feline model of HIV, infection of neonatal cats with the feline immunodeficiency virus, showed development of peripheral neuropathy characterized by loss of epidermal innervation.
While epidemiological studies of HIV-associated peripheral neuropathy continue to provide useful information, pathogenic studies are moving forward. Animal models of the disease will allow researchers to 'manipulate' the system. It is hoped that these types of studies will translate to an improved understanding of the pathogenesis of HIV-associated neuropathies leading to better treatments.
描述HIV神经病变的最新进展。
自高效抗逆转录病毒治疗引入以来的流行病学研究表明,HIV相关远端感觉性多发性神经病变的发病率有所降低。研究还表明了远端感觉性多发性神经病变与使用神经毒性抗逆转录病毒药物之间的关系。用于评估表皮神经纤维密度的皮肤打孔活检对于远端感觉性多发性神经病变的诊断以及作为未来发生该疾病的预测指标均具有重要价值。抗逆转录病毒毒性神经病变的体外模型显示,导致神经病变的双脱氧核苷类似物会产生直接的线粒体毒性,这种毒性并非通过抑制DNA聚合酶γ间接介导。HIV包膜蛋白gp120直接或通过神经周雪旺细胞间接发挥轴突毒性作用。一种HIV猫模型,即新生猫感染猫免疫缺陷病毒,显示出以表皮神经支配丧失为特征的周围神经病变的发展。
虽然HIV相关周围神经病变的流行病学研究继续提供有用信息,但发病机制研究也在不断推进。该疾病的动物模型将使研究人员能够“操控”这个系统。希望这类研究能够增进对HIV相关神经病变发病机制的理解,从而带来更好的治疗方法。