vasoactive-intestinal-peptide and Encephalitis

A hallmark in most neurological disorders is a massive neuronal cell death, in which uncontrolled immune response is usually involved, leading to neurodegeneration. The vasoactive intestinal peptide (VIP) is a pleiotropic peptide that combines neuroprotective and immunomodulatory actions. Alterations on VIP/VIP receptors in patients with neurodenegerative diseases, together with its involvement in the development of embryonic nervous tissue, and findings found in VIP-deficient mutant mice, have showed the relevance of this endogenous peptide in normal physiology and in pathologic states of the central nervous system (CNS). In this review, we will summarize the role of VIP in normal CNS and in neurological disorders. The studies carried out with this peptide have demonstrated its therapeutic effect and render it as an attractive candidate to be considered in several neurological disorders linked to neuroinflammation or abnormal neural development.

Topics: Alzheimer Disease; Animals; Autistic Disorder; Brain; Brain Injuries; Developmental Disabilities; Down Syndrome; Encephalitis; Female; Fetal Alcohol Spectrum Disorders; Humans; Mice; Multiple Sclerosis; Nervous System Diseases; Neuroprotective Agents; Parkinson Disease; Pregnancy; Receptors, Vasoactive Intestinal Peptide; Vasoactive Intestinal Peptide

Topics: Amygdala; Animals; Case-Control Studies; Diet, High-Fat; Down-Regulation; Encephalitis; Hippocampus; Hypothalamus; Male; Metformin; Mice; Mice, Inbred C57BL; Pituitary Adenylate Cyclase-Activating Polypeptide; Prefrontal Cortex; Signal Transduction; Vasoactive Intestinal Peptide

Neuroinflammation is implicated in cerebral vasospasm and brain injuries after subarachnoid hemorrhage (SAH). In addition to classical neuroinflammation with increased inflammatory cytokines, a sterile neurogenic inflammation characterized by release of potent vasoactive neuropeptides may be responsible for brain injuries after SAH. Sympathetic discharges from superior cervical ganglion contribute to vasoconstriction of cerebral arteries Thus, we investigated the effects of surgical cervical sympathectomy on the neurogenic inflammatory neuropeptides shortly after SAH induction in a model of SAH in rats.. Male Wistar rats were divided into 4 groups: control; was not touched, saline group; 300 μl of saline was injected into prechiasmatic cistern, SAH+Sham group; 300 μl of autologous blood was injected to induce subarachnoid hemorrhage into prechiasmatic cistern; SAH+Symp group; the left cervical sympathetic branch was surgically removed after the induction of SAH. Levels of neuropeptides CGRP, SP and VIP which are responsible for neurogenic inflammation, in plasma, trigeminal ganglion, brainstem and brain tissue were measured by ELISA. In addition, c-fos expression as a marker of neuronal activation in the trigeminal nucleus caudalis (TNC) was determined by immunohistochemical staining.. SAH significantly increased c-fos expression in the TNC, as well as CGRP, SP and VIP concentrations in plasma and trigeminal ganglion neurons, and also CGRP and SP concentrations in the brainstem. Cervical sympathectomy application significantly reduced the increases in these parameters induced by SAH.. Our findings suggest that cervical sympathectomy treatment may prevent early brain injury by modulating SAH-induced neurogenic inflammatory neuropeptides such as CGRP, SP and VIP, and improve the quality of life in survivors following SAH.

Topics: Animals; Calcitonin Gene-Related Peptide; Encephalitis; Ganglionectomy; Inflammation Mediators; Male; Neuropeptides; Rats, Wistar; Subarachnoid Hemorrhage; Substance P; Sympathetic Nervous System; Trigeminal Ganglion; Trigeminal Nuclei; Vasoactive Intestinal Peptide

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.

Topics: Animals; Coculture Techniques; Encephalitis; Mice; Microglia; Models, Neurological; Neurodegenerative Diseases; Neurons; Neuroprotective Agents; Vasoactive Intestinal Peptide

Microglia react to even minor disturbances in CNS homeostasis and function as critical regulators of CNS inflammation. Activated microglia secrete inflammatory mediators such as cytokines and chemokines, which contribute to the pathophysiological changes associated with several neuroimmunologic disorders. Microglia-derived inflammatory chemokines recruit various populations of immune cells, which initiate and maintain the inflammatory response against foreign antigens. Entry and retention of activated immune cells in the CNS is a common denominator in a variety of traumatic, ischemic, and degenerative diseases. Vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase-activating polypeptide (PACAP) are two structurally related neuropeptides that function as potent anti-inflammatory factors in the periphery. Here we investigated the effects of VIP and PACAP on chemokine production by activated microglia. VIP and PACAP inhibit the expression of the microglia-derived CXC chemokines MIP-2 and KC, and of the CC chemokines MIP-1alpha, -1beta, MCP-1, and RANTES. The inhibition of chemokine gene expression correlates with an inhibitory effect of VIP/PACAP on NFkB binding. The VIP/PACAP inhibition of both chemokine production and of NFkB binding is mediated through the specific receptor VPAC1 and involves a cAMP-dependent intracellular pathway. Of biological significance is the fact that the inhibition of chemokine production by VIP/PACAP leads to a significant reduction in the chemotactic activity generated by activated microglia for peripheral leukocytes, i.e., neutrophils, macrophages, and lymphocytes. Because reduction in the number and activation of infiltrating leukocytes represents an important factor in the control of inflammation in the CNS, VIP and/or PACAP released by neurons during an inflammatory response could serve as neuronal survival factors by limiting the inflammatory process.

Topics: Animals; Animals, Newborn; Binding Sites; Brain; Cells, Cultured; Chemokines; Chemokines, CC; Chemokines, CXC; Chemotaxis; Cyclic AMP; Cytokines; Encephalitis; Enzyme Inhibitors; Lipopolysaccharides; Macrophage Activation; Mice; Mice, Inbred BALB C; Microglia; Neuropeptides; NF-kappa B; Pituitary Adenylate Cyclase-Activating Polypeptide; Promoter Regions, Genetic; Receptors, Vasoactive Intestinal Peptide; Receptors, Vasoactive Intestinal Polypeptide, Type I; RNA, Messenger; Signal Transduction; Vasoactive Intestinal Peptide