Vasoactive intestinal peptide prevents activated microglia-induced neurodegeneration under inflammatory conditions: potential therapeutic role in brain trauma.
نویسندگان
چکیده
In most neurodegenerative disorders, including multiple sclerosis, Parkinson's disease, and Alzheimer's disease, a massive neuronal cell death occurs as a consequence of an uncontrolled inflammatory response, where activated microglia and its cytotoxic agents play a crucial pathologic role. Because current treatments for these diseases are not effective, several regulatory molecules termed "microglia-deactivating factors" recently have been the focus of considerable research. Vasoactive intestinal peptide (VIP) is a neuropeptide with a potent anti-inflammatory effect, which has been found to protect from other inflammatory disorders, such as endotoxic shock and rheumatoid arthritis. In the present study, we investigate the effect of VIP on inflammation-mediated neurodegeneration in vitro and in vivo as well as on the putative neuroprotective effect of VIP on experimental pathological conditions in which central nervous system (CNS) inflammation is involved, such as brain trauma. The involvement of activated microglia and their derived cytotoxic products is also studied. VIP has a clear neuroprotective effect on inflammatory conditions by inhibiting the production of microglia-derived proinflammatory factors (tumor necrosis factor alpha, interleukin-1beta, nitric oxide). In this sense, VIP prevents neuronal cell death following brain trauma by reducing the inflammatory response of neighboring microglia. Therefore, VIP emerges as a valuable neuroprotective agent for the treatment of pathologic conditions of the CNS where inflammation-induced neurodegeneration occurs.
منابع مشابه
Neuroprotective effect of vasoactive intestinal peptide (VIP) in a mouse model of Parkinson's disease by blocking microglial activation.
Parkinson's disease (PD) is a common neurodegenerative disorder with no effective protective treatment, characterized by a massive degeneration of dopaminergic neurons in the substantia nigra (SNpc) and the subsequent loss of their projecting nerve fibers in the striatum. To elucidate PD pathogenic factors, and thus to develop therapeutic strategies, a murine PD model based on the administratio...
متن کاملP108: Microglia in Traumatic Brain Injury
Microglia is one of the first innate immune components. These cells account about 5 to 10% of the entire adult brain cells and are activated by trauma. Complex-mediated inflammatory responses occur through cellular and molecular events during and after the traumatic brain injury (TBI). In-lesion area astrocytes, microglia, and damaged neurons begin to secrete cytokines and chemokines. Microglia...
متن کاملVasoactive intestinal peptide and pituitary adenylate cyclase-activating polypeptide inhibit the production of inflammatory mediators by activated microglia.
Microglia play a central role in the regulation of immune and inflammatory activities, as well as tissue remodeling in the central nervous system. However, activation of microglia is a histopathological hallmark of several neurodegenerative diseases. Pathological microglial activation is believed to contribute to progressive damage in neurodegenerative diseases through the release of proinflamm...
متن کاملP 133: Neuroinflammation in Alzheimer ’s Disease
Alzheimer’s disease (AD) is a neurodegenerative disorder and the most common form of dementia. Almost 47 million people suffer from dementia worldwide. AD accounts for approximately 60%–80% of all dementia cases. Three major pathologies characterize the disease: senile plaques, neurofibrillary tangles and inflammation. We review the literature on events contributing to the inflammat...
متن کاملVIP Enhances Phagocytosis of Fibrillar Beta-Amyloid by Microglia and Attenuates Amyloid Deposition in the Brain of APP/PS1 Mice
Vasoactive intestinal peptide (VIP) is a multifunctional neuropeptide with demonstrated immunosuppressive and neuroprotective activities. It has been shown to inhibit Amyloid beta (Aβ)-induced neurodegeneration by indirectly suppressing the production and release of a variety of inflammatory and neurotoxic factors by activated microglia. We demonstrated that VIP markedly increased microglial ph...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
عنوان ژورنال:
- FASEB journal : official publication of the Federation of American Societies for Experimental Biology
دوره 17 13 شماره
صفحات -
تاریخ انتشار 2003