Brain, behavior, and immunity
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Brain Behav. Immun. · Jan 2013
Upregulation of α-synuclein during localized radiation therapy signals the association of cancer-related fatigue with the activation of inflammatory and neuroprotective pathways.
Neuroinflammatory mechanisms are associated with fatigue in neurodegenerative conditions such as Parkinson's. The symptoms in Parkinson's including fatigue are thought to be related to α-synuclein overexpression. This study investigated genomic correlates of fatigue experienced by men with prostate cancer receiving external beam radiation therapy (EBRT). ⋯ Fatigue experienced during EBRT may be mediated by α-synuclein overexpression. Alpha-synuclein may serve as a useful biomarker to understand the mechanisms and pathways related to the development of fatigue in this population.
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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. · Aug 2012
Individually ventilated cages cause chronic low-grade hypoxia impacting mice hematologically and behaviorally.
Use of individually ventilated caging (IVC) systems for mouse-based laboratory investigation has dramatically increased. We found that without mice present, intra-cage oxygen concentration was comparable (21%) between IVC housing and ambient environment caging (AEC) that used wire top lids. However, when mice were housed 4-to-a-cage for 1week, intra-cage oxygen dropped to 20.5% in IVC housing as compared to 21% for AEC housing. ⋯ IVC mice, relative to AEC mice, had increased saccharin preference and increased fluid consumption but similar locomotion, food intake, social exploration and novel object recognition when tested in an AEC environment. Taken together, these data indicate that ventilated caging systems can have a 0.5% reduction from ambient oxygen concentration that is coupled to mouse red blood cell indices indicative of chronic exposure to a hypoxia. Importantly, IVC housing can impact behavioral testing for depressive-like behavior.
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Brain Behav. Immun. · Aug 2012
Heterogeneity of macrophages in injured trigeminal nerves: cytokine/chemokine expressing vs. phagocytic macrophages.
Macrophages are important immune effector cells in both innate and adaptive immune responses. Injury to peripheral nerves triggers activation of resident macrophages and infiltration of haematogenous macrophages, which they play critical roles in Wallerian degeneration and neuropathic pain. As macrophages are able to change their phenotypes in response to environment cues, we attempt to identify distinct phenotypes of macrophages in injured nerves and to understand the potential contribution of each macrophage subpopulation to the genesis of neuropathic pain associated with nerve injury. ⋯ Our results highlighted the heterogeneity and the plasticity of macrophages in response to the injury and provided further information on their potential involvement in neuropathic pain. Exploring the full spectrum of macrophage phenotypes in injured nerve is necessary. Individual macrophage population may be selectively targeted by cell-specific intervention for an effective treatment of neuropathic pain.