Brain research
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We report the characterization of a new class of glutamate uptake inhibitors isolated from Phoneutria nigriventer venom. Glutamate transport activity was assayed in rat cerebrocortical synaptosomes by using [(3)H]-L-glutamate. ⋯ The IC(50) value obtained was 2.35+/-0.9 microg/ml which is in the observed range reported for glutamate uptake blockers. Tx4-7, one of PhTx4 toxins, showed the strongest inhibitory activity (50.3+/-0.69%, n=3).
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Comparative Study
Acute peripheral inflammation induces moderate glial activation and spinal IL-1beta expression that correlates with pain behavior in the rat.
Our laboratory has previously shown that glial activation and increased proinflammatory cytokine expression are observed in the rat spinal cord following peripheral nerve injuries that result in neuropathic pain behaviors. In the present study, we sought to determine whether acute peripheral inflammation induces changes in central glial and cytokine (Interleukin-1beta) expression similar to those seen following peripheral spinal nerve transection. Two models of peripheral inflammation were used in this study: formalin (5% solution) or zymosan (25 mg/ml) injected subcutaneously into the plantar portion of the left hind paw of male Holtzman-strain Sprague-Dawley rats. ⋯ Spinal sections from both formalin and zymosan treated animals exhibited microglial and astrocytic activation and increased Interleukin-1beta immunoreactivity at 1 and 6 h, respectively. Spinal glial activation and upregulation of Interleukin-1beta appear to parallel the development and maintenance of zymosan and formalin-induced mechanical allodynia. These findings support a unifying theory that glial activation and cytokine expression have a similar, if not related, role in producing hyperalgesia following either peripheral inflammation or peripheral nerve injury.
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Comparative Study
Comparison of cerebral blood flow and injury following intracerebral and subdural hematoma in the rat.
Subdural hematomas (SDH) can induce ischemia and neuronal damage in the underlying cortex. However, the extent to which intracerebral hematomas (ICH) produce reductions in cerebral blood flow (CBF) sufficient to cause ischemic damage is uncertain. Intracranial hemorrhage was induced by the injection of 100 or 200 microl of blood into the subdural space (SDH) or into the caudate nucleus (ICH) of the rat. ⋯ Increases in brain water content after SDH, were confined to the cerebral cortex (sham: 0.1+/-0.1 g/g dry weight; 200 microl: 0.8+/-0.3 g/g dry weight; P<0.001). In contrast, increases in brain water content after ICH were predominantly in the subcortical region (sham: 0.1+/-0.1 g/g dry weight; 200 microl: 0.4+/-0.2 g/g dry weight; P<0.01). The present investigations demonstrate differences in CBF, brain injury and edema formation following SDH and ICH indicating that these conditions may require different therapeutic interventions.
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Poly(ADP-ribose) polymerase (PARP) is thought to play a physio-logical role in maintaining genomic integrity and in the repair of DNA strand breaks. However, the activation of PARP by free radical-damaged DNA plays a pivotal role in mediating ischemia-reperfusion injury. The excessive activation of PARP causes a rapid depletion of intracellular energy leading to cell death. ⋯ PARP inhibition lead to a significant decrease in damaged volume in all treated groups with the largest reduction in the 40 mg/kg group (111.5+/-24. 8 mm3, mean+/-SD, p<0.01), compared to the control group (193.5+/-28. 6 mm3). We also found there was a significant increase of poly(ADP-ribose) immunoreactivity in the ischemic region, as compared to the contralateral side, with DPQ treatment diminishing poly(ADP-ribose) production. These findings indicate that DPQ exerts its neuroprotective effects in vivo by PARP inhibition and that PARP inhibitors may be effective for treating ischemic stroke, even when the treatment is initiated after the onset of ischemia.
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In spite of several reports about suppressive effects of volatile anesthetics on somatosensation, their neuronal mechanisms are largely unknown. The present study investigates somatosensory impulse transmission at the thalamic level in rats under varied concentrations of isoflurane by recordings of neuronal responses to mechanical stimulation of the body surface. Single-unit recordings of thalamo-cortical relay neurons (TCNs, third order neurons; n=28) and presumed trigemino-thalamic fibers (TTFs, second order neurons; n=7) were performed in the ventral posteromedial nucleus. ⋯ In contrast, the tonic and sustained response characteristics of TTFs were preserved even at higher isoflurane concentrations. The results indicate that isoflurane attenuates the output of somatosensory signals in the specific nucleus of the rat's thalamus, while its input is only marginally affected. The observed changes of thalamic neuronal response characteristics, at least in part, may cause the loss in sensory discrimination observed during general anesthesia.