Brain research
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It has been demonstrated that spinal microglial activation is involved in formalin-induced pain and that minocycline, an inhibitor of microglial activation, attenuate behavioral hypersensitivity in neuropathic pain models. We investigated whether minocycline could have any anti-nociceptive effect on inflammatory pain, after intraperitonial administration of minocycline, 1 h before formalin (5%, 50 microl) injection into the plantar surface of rat hindpaw. Minocycline (15, 30, and 45 mg/kg) significantly decreased formalin-induced nociceptive behavior during phase II, but not during phase I. ⋯ Analysis with OX-42 antibody revealed the inhibitory effect of minocycline on microglial activation 3 days after formalin injection. These results demonstrate the anti-nociceptive effect of minocycline on formalin-induced inflammatory pain. In addition to the well-known inhibitory action of minocycline on microglial activation, the anti-edematous action in peripheral tissue, as well as the inhibition of synaptic transmission in SG neurons, is likely to be associated with the anti-nociceptive effect of minocycline.
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Norepinephrine, acting via beta-adrenoceptors, enhances the perforant path-evoked potential in dentate gyrus. Using systemic idazoxan to increase norepinephrine, and paired perforant path pulses to probe early inhibition, previous investigators reported that idazoxan increased initial spike amplitude and increased somatic feedback inhibition. Here, feedback inhibition was re-examined in idazoxan-treated (5 mg/kg) rats under urethane anesthesia. ⋯ Decreased EPSP slope ratios with similar paired pulse intervals have been reported in novel environments. Since exposure to novel environments activates locus coeruleus neurons, norepinephrine may mediate the change in EPSP slope inhibition reported in awake rats. In summary, these results are consistent with the hypothesis that idazoxan potentiates granule cell responses to perforant path input in the dentate gyrus via increases in norepinephrine that lead to beta-adrenoceptor activation, and, further, that idazoxan reduces paired pulse feedback spike facilitation and enhances EPSP slope, but not spike, feedback inhibition.
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Comparative Study
Arterial hypotension triggers perifocal depolarizations and aggravates secondary damage in focal brain injury.
Perifocal depolarizations (PFD) have been observed after traumatic brain injury, are known to disturb cerebrovascular reactivity and thus may contribute to the morphological consequences of brain injury. In this investigation, the role of PFD was studied in focal brain lesions with/without induction of delayed hypotension. Cerebral freeze lesions were induced in anesthetized normotensive rats that underwent perfusion fixation of brains 5 min, 4 h or 24 h after lesioning, respectively, to obtain quantitative histopathology. ⋯ In 6 of 8 rats that underwent cold lesion plus hypotension, a second PFD was observed approximately 2.5 min after onset of hypotension accompanied by a relative LDF increase by 25 +/- 12%. Lesion expansion was significantly worsened by hypotension (8.19 +/- 0.56 mm(3) at 24 h) compared with normotensive rats (7.01 +/- 0.3 mm(3) at 24 h, P < 0.01). We conclude that hypotension triggers depolarizations by an ischemic mechanism that contributes to final tissue damage.
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Comparative Study
Adenosine treatment delays postischemic hippocampal CA1 loss after cardiac arrest and resuscitation in rats.
Resuscitation from cardiac arrest results in reperfusion injury that leads to increased postresuscitation mortality and delayed neuronal death. One of the many consequences of resuscitation from cardiac arrest is a derangement of energy metabolism and the loss of adenylates, impairing the tissue's ability to regain proper energy balance. In this study, we investigated the effects of adenosine (ADO) on the recovery of the brain from 12 min of ischemia using a rat model of cardiac arrest and resuscitation. ⋯ Our findings suggested that improved postischemic brain blood flow and ADO-induced hypothermia, rather than adenylate supplementation, may be the two major contributors to the neuroprotective effects of adenosine following cardiac arrest and resuscitation. Although adenosine did not prevent eventual CA1 neuronal loss in the long term, it did delay neuronal loss and promoted long-term survival. Thus, adenosine or specific agonists of adenosine receptors should be evaluated as adjuncts to broaden the window of opportunity in the treatment of the reperfusion injury following cardiac arrest and resuscitation.