Brain research
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Activated Protein C renders anti-apoptotic properties in neurons and endothelial cells. The aim of the present study was to evaluate the in vivo cytoprotective role of Protein C zymogen (PC) administration in septic rat brain. Male Wistar rats (n=60) were subjected to sepsis via Cecal Ligation and Puncture (CLP). ⋯ In addition, active caspase 3, bax, cytochrome c and caspase 8 expression was significantly decreased during early sepsis (6-36 h) while bcl-2 expression was increased (24 h p=0.001 and 60 h p=0.001) in the PC treated animals compared to placebo. PC concentrate administration in experimental sepsis produced a time dependent inhibition of apoptosis in rat neurons and astrocytes. The inhibition of sepsis related apoptosis concerned both the mitochondrial and caspase 8 dependent pathways.
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The present study investigated the effects of systemic administration of dexmedetomidine, a selective alpha2 adrenergic receptor (alpha2AR) agonist, and gabapentin either alone or in combination on thermal hyperalgesia evoked by ankle joint inflammation. Monoarthritis of rat ankle joint was induced by an intra-articular injection of Complete Freund's Adjuvant (CFA). The paw withdrawal latency (PWL) from a thermal stimulus was measured in awake rats. ⋯ The PWLs of the non-injected and normal saline (NS)-injected hindpaws were not significantly affected by the two agents at the most doses tested except the highest dose of dexmedetomidine (20 microg/kg). Although low dose of dexmedetomidine (2.5 microg/kg) or gabapentin (25 mg/kg) alone did not affect or lightly increased PWLs of the hindpaw ipsilateral to CFA-injected joint, a combination of dexmedetomidine and gabapentin (2.5 microg/kg+25 mg/kg, or 5 microg/kg+50 mg/kg) significantly reversed CFA-induced thermal hyperalgesia for 60 min without sedation/motor impairment. These results provide the first identification that co-application of dexmedetomidine and gabapentin may synergistically antagonize inflammatory pain, and this might prove to be beneficial in the treatment of arthritic pain.
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In a recent study we found that 4 weeks of human experimental forearm immobilization induced hypersensitivity to mechanical and cold stimuli and a higher skin temperature on the immobilized hand. Identical findings are reported in immobilization studies in rats where increased substance P signaling is suggested to play a central role. Capsaicin releases substance P from axon collaterals in the periphery initiating vasodilatation and plasma extravasation. ⋯ Time to sensory detection of capsaicin and pain onset was significantly increased on the immobilized left hand. Immobilization significantly reduced capsaicin-evoked pain, neurogenic flare area, and skin blood flow (perfusion units), and the reduced capsaicin-evoked pain was significantly correlated to an increase in peripheral skin temperature but not to skin blood flow. The correlation between reduced capsaicin-evoked pain and increased skin temperature suggests an increased substance P release while the delayed onset and diminished magnitude of capsaicin-induced pain may be due to reduced penetration of capsaicin into the epidermis.
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Traumatic brain injury (TBI) is a major cause of death and disability worldwide; however, no effective treatment has been clinically identified. Our recent studies show that the combination of collagen scaffolds with human bone morrow stromal cells (hMSCs) for treatment of TBI improves functional outcome and reduces the lesion volume when this combination was applied at day 4 after TBI in rats. The mechanisms underlying these benefits remain unclear. ⋯ Corticocortical labeling with 1, 1''-dioleyl-3, 3, 3'', 3''-tetramethylindocarbocyanine methanesulfonate (DiI) was performed at day 36 after TBI. The rats were sacrificed 43 days after TBI, and the brain tissue was processed for DiI-labeling fiber and immunohistochemical analyses. The present data show that delayed transplantation of hMSCs or scaffolds seeded with hMSCs improved spatial learning and sensorimotor function, enhanced angiogenesis in the injured cortex and the ipsilateral hippocampus and increased DiI-labeled neural fiber length in the injured cortex. hMSC-seeded scaffolds may be a new and effective way to improve neurological function after TBI.
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In the present study, the activation of extracellular signal-regulated kinase (ERK) in the locus coeruleus (LC) following injection of formalin or complete Freund's adjuvant (CFA) into the rat hindpaw was examined in order to clarify the mechanisms underlying the dynamic changes in the descending pain modulatory system after acute noxious stimulation or chronic inflammation. In naive rats there were few phospho-extracellular signal-regulated kinase-immunoreactive (p-ERK-IR) neurons in the LC. Formalin-, CFA- and saline-injections induced an increase in p-ERK-IR in the LC. ⋯ At 5 min after formalin injection, almost all p-ERK-IR neurons in the LC were tyrosine hydroxylase (TH) -positive. These findings suggest that activation of ERK in the LC is induced by acute noxious stimulation, such as formalin injection, but not by CFA-induced chronic inflammation. The activation of ERK in the LC may be involved in the plasticity of the descending pain modulatory systems following acute noxious stimulation.