Brain, behavior, and immunity
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Brain Behav. Immun. · Nov 2012
ReviewNeuroinflammation after traumatic brain injury: opportunities for therapeutic intervention.
Traumatic brain injury (TBI) remains one of the leading causes of mortality and morbidity worldwide, yet despite extensive efforts to develop neuroprotective therapies for this devastating disorder there have been no successful outcomes in human clinical trials to date. Following the primary mechanical insult TBI results in delayed secondary injury events due to neurochemical, metabolic and cellular changes that account for many of the neurological deficits observed after TBI. The development of secondary injury represents a window of opportunity for therapeutic intervention to prevent progressive tissue damage and loss of function after injury. ⋯ The key to developing future anti-inflammatory based neuroprotective treatments for TBI is to minimize the detrimental and neurotoxic effects of neuroinflammation while promoting the beneficial and neurotrophic effects, thereby creating optimal conditions for regeneration and repair after injury. This review outlines how post-traumatic neuroinflammation contributes to secondary injury after TBI, and discusses the complex and varied responses of the primary innate immune cells of the brain, microglia, to injury. In addition, emerging experimental anti-inflammatory and multipotential drug treatment strategies for TBI are discussed, as well as some of the challenges faced by the research community to translate promising neuroprotective drug treatments to the clinic.
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Brain Behav. Immun. · Oct 2012
ReviewThinking through postoperative cognitive dysfunction: How to bridge the gap between clinical and pre-clinical perspectives.
Following surgery, patients may experience cognitive decline, which can seriously reduce quality of life. This postoperative cognitive dysfunction (POCD) is mainly seen in the elderly and is thought to be mediated by surgery-induced inflammatory reactions. Clinical studies tend to define POCD as a persisting, generalised decline in cognition, without specifying which cognitive functions are impaired. ⋯ The most important outcomes are: (1) POCD encompasses a wide range of cognitive impairments; (2) POCD affects larger areas of the brain; and (3) individual variation in the vulnerability of neuronal networks to neuroinflammatory mechanisms may determine if and how POCD manifests itself. We argue that, for pre-clinical and clinical research of POCD to advance, the effects of surgery on various cognitive functions and brain areas should be studied. Moreover, in addition to general characteristics, research should take inter-relationships between cognitive complaints and physical and mental characteristics into account.
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Brain Behav. Immun. · Feb 2012
ReviewNeuroimmunological effects of physical exercise in depression.
The search for an extended understanding of the causes of depression, and for the development of additional effective treatments is highly significant. Clinical and pre-clinical studies suggest stress is a key mediator in the pathophysiology of depression. Exercise is a readily available therapeutic option, effective as a first-line treatment in mild to moderate depression. ⋯ When clinical and pre-clinical data is taken together, exercise may reduce inflammation and oxidation stress via a multitude of cellular and humoral neuroimmune changes. Astrocytes, microglia and T cells have an antiinflammatory and neuroprotective functions via a variety of mechanisms. It is unknown whether exercise has effects on specific neuroimmune markers implicated in the pathogenesis of depression such as markers of immunosenescence, B or T cell reactivity, astrocyte populations, self-specific CD4+ T cells, T helper 17 cells or T regulatory cells.
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Brain Behav. Immun. · Oct 2011
ReviewPeripheral immune contributions to the maintenance of central glial activation underlying neuropathic pain.
Recent evidence implicates an adaptive immune response in the central nervous system (CNS) mechanisms of neuropathic pain. This review identifies how neuropathic pain alters CNS immune privilege to facilitate T cell infiltration. ⋯ In this way, T cells may contribute to the maintenance of neuropathic pain through pro-inflammatory interactions with microglia and by facilitating the activation of astrocytes in the spinal dorsal horn. Based on the evidence presented in this review, we suggest that this bidirectional, pro-inflammatory system of neurons, glia and T cells in neuropathic pain should be renamed the pentapartite synapse, and identifies the latest member as a potential disease-modifying therapeutic target.
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Brain Behav. Immun. · Mar 2011
ReviewAbdominal pain in Irritable Bowel Syndrome: a review of putative psychological, neural and neuro-immune mechanisms.
Chronic abdominal pain is a common symptom of great clinical significance in several areas of medicine. In many cases no organic cause can be established resulting in the classification as functional gastrointestinal disorder. Irritable Bowel Syndrome (IBS) is the most common of these conditions and is considered an important public health problem because it can be disabling and constitutes a major social and economic burden given the lack of effective treatments. ⋯ At the same time, there is growing evidence linking peripheral and mucosal immune changes and abdominal pain in IBS, supporting disturbed peripheral pain signalling. Findings in post-infectious IBS emphasize the interaction between centrally-mediated psychosocial risk factors and local inflammation in predicting long-term IBS symptoms. Investigating afferent immune-to-brain communication in visceral hyperalgesia as a component of the sickness response constitutes a promising future research goal.