The neurovascular units (NVU) are the minimal functional units of the blood­–brain barrier (BBB), composed of endothelial cells, pericytes, astrocytes, microglia, neurons, and the basement membrane. The BBB serves as an important interface for immune communication between the brain and peripheral circulation. Disruption of the NVU by the human immunodeficiency virus-1 (HIV-1) induces dysfunction of the BBB and triggers inflammatory responses, which can lead to the development of neurocognitive impairments collectively known as HIV-1-associated neurocognitive disorders (HAND). Methamphetamine (METH) use disorder is a frequent comorbidity among individuals infected with HIV-1. METH use may be associated not only with rapid HIV-1 disease progression but also with accelerated onset and increased severity of HAND. However, the molecular mechanisms of METH-induced neuronal injury and cognitive impairment in the context of HIV-1 infection are poorly understood. In this review, we summarize recent progress in the signaling pathways mediating synergistic impairment of the BBB and neuronal injury induced by METH and HIV-1, potentially accelerating the onset or severity of HAND in HIV-1-positive METH abusers. We also discuss potential therapies to limit neuroinflammation and NVU damage in HIV-1-infected METH abusers.

中文翻译：

---

HIV-1 感染和甲基苯丙胺使用对神经血管单元的协同损害：对 HIV-1 相关神经认知障碍的影响

神经血管单位 (NVU) 是血脑屏障 (BBB) 的最小功能单位，由内皮细胞、周细胞、星形胶质细胞、小胶质细胞、神经元和基底膜组成。BBB 是大脑和外周循环之间免疫通讯的重要接口。人类免疫缺陷病毒 1 (HIV-1) 对 NVU 的破坏会导致 BBB 功能障碍并引发炎症反应，这可能导致神经认知障碍的发展，统称为 HIV-1 相关神经认知障碍 (HAND)。甲基苯丙胺 (METH) 使用障碍是 HIV-1 感染者常见的合并症。METH 的使用可能不仅与 HIV-1 疾病的快速进展有关，而且与 HAND 的加速发病和严重程度增加有关。然而，在 HIV-1 感染的情况下，METH 诱导的神经元损伤和认知障碍的分子机制知之甚少。在这篇综述中，我们总结了介导 METH 和 HIV-1 诱导的 BBB 协同损伤和神经元损伤的信号通路的最新进展，可能加速 HIV-1 阳性 METH 滥用者手部的发病或严重程度。我们还讨论了限制 HIV-1 感染 METH 滥用者的神经炎症和 NVU 损伤的潜在疗法。