Atlanta VA Medical Center, Decatur, GA, USA.
Department of Neurology, Emory University School of Medicine, Atlanta, GA, USA.
J Neurovirol. 2018 Apr;24(2):180-184. doi: 10.1007/s13365-017-0572-6. Epub 2017 Sep 11.
HIV-associated neurocognitive disorders (HAND) remain highly prevalent despite combined antiretroviral therapy (cART). Although the most common forms of HAND are mild and identified through neuropsychological testing, there is evidence that with aging these mild forms become more prevalent and may advance to the most severe form of HAND, HIV-associated dementia. Therefore, novel therapies must be developed that can be used adjunctively with cART to prevent deterioration or restore normal cognitive function. In order to develop innovative treatments, animal models are used for preclinical testing. Ideally, a HAND animal model should portray similar mild cognitive deficits that are found in humans. A mouse model of HAND is discussed, which demonstrates mild behavioral deficits and has been used to investigate cART and novel treatments for HAND. This model also shows correlations between abnormal mouse behavior due to HIV in the brain and pathological parameters such as gliosis and neuronal abnormalities. A recent advancement utilizes the object recognition test to monitor mouse behavior before and after treatment. It is postulated that this model is well suited for preclinical testing of novel therapies and provides correlations of mild cognitive impairment with pathological markers that can give further insight into the pathophysiology of HAND.
尽管联合抗逆转录病毒疗法（cART）已经广泛应用，但与艾滋病相关的神经认知障碍（HAND）仍然高度流行。尽管 HAND 的最常见形式是轻度的，可以通过神经心理学测试来识别，但有证据表明，随着年龄的增长，这些轻度形式变得更加普遍，并可能发展为 HAND 最严重的形式，即艾滋病相关痴呆。因此，必须开发新的治疗方法，与 cART 联合使用，以预防病情恶化或恢复正常认知功能。为了开发创新疗法，人们使用动物模型进行临床前测试。理想情况下，HAND 的动物模型应该能够模拟出人类中发现的类似轻度认知缺陷。本文讨论了一种 HAND 小鼠模型，该模型显示出轻度的行为缺陷，并已被用于研究 HAND 的 cART 和新型治疗方法。该模型还显示了 HIV 在大脑中引起的异常小鼠行为与神经胶质增生和神经元异常等病理参数之间的相关性。最近的一项进展利用物体识别测试来监测治疗前后小鼠的行为。据推测，该模型非常适合新型治疗方法的临床前测试，并将轻度认知障碍与病理标志物相关联，从而进一步深入了解 HAND 的病理生理学。
