HIV neuropathogenesis and therapeutic strategies.
HIV neuropathogenesis and therapeutic strategies.
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HIV 神经发病机制和治疗策略。
DOI：
10.1111/j.1442-200x.1998.tb01892.x
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发表时间：
1998
期刊：
影响因子：
--
通讯作者：
Epstein,LG
中科院分区：
文献类型：
--
作者：
Epstein,LG
Human immunodeficiency virus (HIV)‐l neuropathogenesis can be divided into three important components: (i) virus entry into the nervous system; (ii) the role of viral proteins and/or cellular products in neural tissue damage; and (iii) the mechanisms of neuronal injury/death. Both blood derived macrophages or trafficking HIV‐1 infected T‐lymphocytes have been implicated in viral entry to the central nervous system (CNS). The major cell type harboring productive HIV‐1 infection in the nervous system is the perivascular macrophage/ microglia. The HIV‐1 infection of brain astrocytes, restricted to the expression of regulatory gene products, may cause astrocyte dysfunction and contribute to neuronal injury or to disruption of the blood‐brain barrier (BBB). Studies of cerebrospinal fluid and postmortem tissues reveal chronic inflammation/immune activation in the nervous system during the later stages of HIV‐1 infection associated with disruption of BBB integrity. Blood‐brain barrier damage may underlie the white matter pallor described in HIV‐1 infection and could result in further entry into the CNS of toxic viral or cellular products, or additional HIV‐1 infected cells. The HIV infected and activated macrophages/microglia produce excessive amounts of pro‐inflammatory cytokines, including tumor necrosis factor alpha, and platelet activating factor. These products are directly toxic to human neuronsin vitro.The HIV‐1 envelope glycoprotein, gp 120 may stimulate the release of toxic factors from brain macrophages. Blocking N‐methyl‐D‐aspartate (NMDA; or AMPA) glutamate receptors can antagonize candidate toxins of both viral and cellular origin. It has been postulated that (weak) excitotoxicity leads to oxidative stress in neurons and ultimately to apoptosis. Neuronal apoptosis occurs in the brains of both children and adults with HIV‐1 infection. This understanding of HIV neuropathogenesis implies that therapeutic strategies should include: (i) anti‐retroviral medications to decrease systemic and CNS virus load, and possibly to prevent perinatal transmission of HIV; (ii) anti‐inflammatory compounds to decrease the chronic immune activation in microglia and allow the restoration of BBB integrity; and (iii) neuroprotective compounds to reduce neuronal injury and apoptotic death.
