Brain, behavior, and immunity
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Brain Behav. Immun. · Feb 2015
Calpain-2 contributes to neuropathic pain following motor nerve injury via up-regulating interleukin-6 in DRG neurons.
Motor nerve injury by L5 ventral root transection (L5-VRT) initiates interleukin-6 (IL-6) up-regulation in primary afferent system contributing to neuropathic pain. However, the early upstream regulatory mechanisms of IL-6 after L5-VRT are still unknown. Here, we monitored both the activity of calpain, a calcium-dependent protease suggested as one of the earliest mediators for cytokine regulation, and the expression of IL-6 in bilateral L4-L6 dorsal root ganglias (DRGs) soon after L5-VRT. ⋯ Inhibition of calpain by pre-treatment with MDL28170 (25mg/kg, i.p.) attenuated the rat mechanical allodynia and prevented the early up-regulation of IL-6 following L5-VRT. Addition of exogenous calpain-2 onto the surface of left L5 DRG triggered a temporal allodynia and increased IL-6 in bilateral DRGs simultaneously. Taken together, the early increase of calpain-2 in L5-VRT rats might be responsible for the induction of allodynia via up-regulating IL-6 in DRG neurons.
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Brain Behav. Immun. · Feb 2015
Programming of formalin-induced nociception by neonatal LPS exposure: Maintenance by peripheral and central neuroimmune activity.
The immune and nociceptive systems are shaped during the neonatal period where they undergo fine-tuning and maturation. Painful experiences during this sensitive period of development are known to produce long-lasting effects on the immune and nociceptive responses. It is less clear, however, whether inflammatory pain responses are primed by neonatal exposure to mild immunological stimuli, such as with lipopolysaccharide (LPS). ⋯ These data suggest neonatal LPS exposure produces developmentally regulated changes in formalin-induced behavioural responses, peripheral and central IL-1β levels, as well as mast cell degranulation following noxious stimulation later in life. These findings highlight the importance of immune activation during the neonatal period in shaping immune response and pain sensitivity later in life. This is of clinical relevance given the high prevalence of bacterial infection during the neonatal period, particularly in the vulnerable population of preterm infants admitted to neonatal intensive care units.
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Brain Behav. Immun. · Jan 2015
The role of microglia activation in the development of sepsis-induced long-term cognitive impairment.
Oxidative stress and inflammation is likely to be a major step in the development of sepsis-associated encephalopathy (SAE) and long-term cognitive impairment. To date, it is not known whether brain inflammation and oxidative damage are a direct consequence of systemic inflammation or whether these events are driven by brain resident cells, such as microglia. Therefore, the aim of this study is to evaluate the effect of minocycline on behavioral and neuroinflammatory parameters in rats submitted to sepsis. ⋯ Treatment with minocycline prevented an increase in markers of oxidative damage and inflammation in the hippocampus after sepsis. This was associated with an improvement in long-term cognitive performance. In conclusion, we demonstrated that the inhibition of the microglia by an ICV injection of minocycline was able to decrease acute brain oxidative damage and inflammation as well as long-term cognitive impairment in sepsis survivors.
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Brain Behav. Immun. · Jan 2015
PsychoNeuroImmunology Research Society's Robert Ader New Investigator Award.
Dr. Aric A. Prather, University of California, San Francisco (UCSF), is the recipient of the 2015 Robert Ader New Investigator Award and will present on his research at the PsychoNeuroImmunology Research Society (PNIRS) meeting, June 3–6, Seattle, WA. The Robert Ader New Investigator Award is presented to an outstanding new research scientist who has made exciting basic science or clinical contributions to the field of psychoneuroimmunology.
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Brain Behav. Immun. · Nov 2014
Identification of a functional interaction of HMGB1 with Receptor for Advanced Glycation End-products in a model of neuropathic pain.
Recent studies indicate that the release of high mobility group box 1 (HMGB1) following nerve injury may play a central role in the pathogenesis of neuropathic pain. HMGB1 is known to influence cellular responses within the nervous system via two distinct receptor families; the Receptor for Advanced Glycation End-products (RAGE) and Toll-like receptors (TLRs). The degree to which HMGB1 activates a receptor is thought to be dependent upon the oxidative state of the ligand, resulting in the functional isoforms of all-thiol HMGB1 (at-HMGB1) acting through RAGE, and disufide HMGB1 (ds-HMGB1) interacting with TLR4. ⋯ Moreover, a single exposure to monoclonal antibody to RAGE (RAGE Ab) failed to abrogate pain behavior at PID 7, 14 and 21. However, RAGE Ab administration produced reversal of mechanical hyperalgesia on PID28. Thus, at-HMGB1 activation through RAGE may be responsible for sensory neuron sensitization and mechanical hyperalgesia associated with chronic neuropathic pain states.