The brain is no longer considered immune-privileged due to its capability of producing cytokines in response to neurotrauma; however, the cellular sources of cytokines have not been defined. This study focused on the production of four inflammatory cytokines, interleukin-1 (IL-1alpha), interleukin-6 (IL-6), tumor necrosis factor alpha (TNFalpha), and interferon gamma (IFN-gamma) in primary culture of astrocytes under two different injury models which simulated in vivo mechanical trauma (scratch injury) and ischemia. Results demonstrated that astrocytes after scratch injury were positively immunostained with IL-1alpha, IL-6, and TNFalpha. A slot-blot study of culture media showed that the release of IL-1alpha, IL-6, TNFalpha, and IFN-gamma by astrocytes subsequent to scratch and ischemic injury reached approximately twice the control values. The temporal expression of these cytokines was different for the two models. All four cytokines began to increase 1 h postscratch and remained at high levels throughout the experiment. In the ischemic model, however, the increase of cytokine expression was delayed until 4-8 h of ischemia, when sharp increases were seen in all four cytokines. In this culture system, the exogenous influence of blood-borne factors and leukocytes, which occur with in vivo trauma and ischemia, was eliminated. Accordingly, the cytokines detected in the culture media were derived from astrocytes. This study provides the first evidence that astrocytes, without the influence from other cell types, can produce and release cytokines following mechanical and ischemic injury.

Alzheimers disease (AD) is a neurodegenerative disease with major clinical hallmarks of memory loss, dementia, and cognitive impairment. Neuroinflammation is involved in the onset of several neurodegenerative disorders. Astrocyte is the most abundant type of glial cells in the central nervous system (CNS) and appears to be involved in the induction of neuroinflammation. Under stress and injury, astrocytes become astrogliotic leading to an upregulation of the expression of proinflammatory cytokines and chemokines, which are associated with the pathogenesis of AD. Cytokines and related molecules play roles in both neuroprotection and neurodegeneration in the CNS. During early AD pathogenesis, amyloid beta (Aβ), S100B and IL-1β could bring about a vicious cycle of Aβ generation between astrocytes and neurons leading to chronic, sustained and progressive neuroinflammation. In advanced stages of AD, TRAIL secreted from astrocytes have been shown to bind to death receptor 5 (DR5) on neurons to trigger apoptosis in a caspase-8-dependent manner. Furthermore, astrocytes could be reactivated by TGFβ1 to generate more Aβ and to undergo the aggravating astrogliosis. TGFβ2 was also observed to cooperate with Aβ to cause neuronal demise by destroying the stability of lysosomes in neurons. Inflammatory molecules can be either potential biomarkers for diagnosis or target molecules for therapeutic intervention. Understanding their roles and their relationship with activated astrocytes is particularly important for attenuating neuroinflammation in the early stage of AD. The main purpose of this review is to provide a comprehensive insight into the role of astrocytes in the neuroinflammatory pathogenesis of AD.