Experimental neurology
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Experimental neurology · Sep 2009
Treatment of intracerebral hemorrhage in rats with 12 h, 3 days and 6 days of selective brain hypothermia.
Intracerebral hemorrhage (ICH) is a devastating stroke with no proven treatment to reduce brain injury. In this study we modeled ICH by injecting 100 microL of autologous blood into the striatum of rats. We then tested whether hypothermia would reduce brain injury and improve recovery as has been repeatedly observed for ischemic and traumatic brain damage. ⋯ Only the limb use asymmetry deficit was significantly mitigated by hypothermia, and then only by the longest treatment. Lesion volume, which averaged 16.9 mm3, was not affected. These results, in conjunction with earlier studies, suggest that prolonged mild hypothermia will not be a profound neuroprotectant for patients with striatal ICH, but it may nonetheless improve functional recovery in addition to its use for treating cerebral edema.
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Experimental neurology · Sep 2009
Post-ischemic leakiness of the blood-brain barrier: a quantitative and systematic assessment by Patlak plots.
The Patlak plot analysis of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) allows estimation of blood-brain barrier (BBB) leakage following temporary focal cerebral ischemia. Thus far, a systematic and quantitative in vivo evaluation of post-ischemic BBB leakage is lacking. Here, using DCE-MRI and the Patlak plot method, we quantitatively assessed BBB leakage in rats at the following time-points after reperfusion: 25 min, 2, 4, 6, 12, 18, 24, 36, 48, and 72 h, and 1, 2, 3, 4, and 5 weeks. ⋯ Both ADC values (r=-0.58, p=0.02) and ischemic lesion volumes (r=0.75, p=0.0015) correlated with K(i) values. These results suggest that after ischemia-reperfusion in rats, BBB leakage is continuous during a 4-week period. Its magnitude diminishes over time and correlates with severity and extent of ischemic injury.
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Experimental neurology · Sep 2009
Colitis induces calcitonin gene-related peptide expression and Akt activation in rat primary afferent pathways.
Previous study has shown that colitis-induced increases in calcitonin gene-related peptide (CGRP) immunoreactivity in bladder afferent neurons result in sensory cross-sensitization. To further determine the effects of colitis on CGRP expression in neurons other than bladder afferents, we examined and compared the levels of CGRP mRNA and immunoreactivity in the lumbosacral dorsal root ganglia (DRG) and spinal cord before and during colitis in rats. We also examined the changes in CGRP immunoreactivity in colonic afferent neurons during colitis. ⋯ In S1 spinal cord, colitis caused the increases in the intensity of CGRP fibers in the regions of dorso-lateral tract, and caused the increases in the level of phospho-Akt in the superficial dorsal horn of the spinal cord. In spinal cord slice culture, exogenous CGRP increased the phosphorylation level of Akt but not the phosphorylation level of extracellular-signal regulated kinase ERK1/2 even though our previous studies showed that colitis increased the phosphorylation level of ERK1/2 in L1 and S1 spinal cord. These results suggest that CGRP is synthesized in the DRG and may transport to the spinal cord where it initiates signal transduction during colitis.
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Experimental neurology · Sep 2009
Behavioral and cognitive alterations, spontaneous seizures, and neuropathology developing after a pilocarpine-induced status epilepticus in C57BL/6 mice.
Many patients with epilepsy suffer from psychiatric comorbidities including depression, anxiety, psychotic disorders, cognitive, and personality changes, but the mechanisms underlying the association between epilepsy and psychopathology are only incompletely understood. Animal models of epilepsy, such as the pilocarpine model of acquired temporal lobe epilepsy (TLE), are useful to study the relationship between epilepsy and behavioral dysfunctions. In the present study, we examined behavioral and cognitive alterations, spontaneous seizures, and neuropathology developing after a pilocarpine-induced status epilepticus in the C57BL/6 (B6) inbred strain of mice, which is commonly used as background strain for genetically modified mice. ⋯ Furthermore, spatial learning and memory were severely impaired in the Morris water maze, although hippocampal damage was much less severe than previously determined in NMRI mice. B6 mice in which pilocarpine did not induce SE but only single seizures did not exhibit any detectable neurodegeneration, but differed behaviorally from sham controls in several tests of the test battery used. Our data indicate that the pilocarpine model of TLE in B6 mice is ideally suited to study the neurobiological mechanisms underlying the association between seizures, brain damage and psychopathology.
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Experimental neurology · Sep 2009
Focal nerve inflammation induces neuronal signs consistent with symptoms of early complex regional pain syndromes.
Early forms of complex regional pain syndromes (CRPS) are characterized by severe pain and autonomic dysfunction in a limb, both of which seem out of proportion to the inciting event. While often caused by obvious nerve injury, the syndromes also occur following relatively trivial trauma. Persistent inflammation has been implicated in the etiology of CRPS. ⋯ Additionally, none of the sympathetic axons in any group were mechanically sensitive. These findings support that focal nerve inflammation is sufficient to cause neuronal discharge changes that are consistent with clinical findings in early CRPS. Furthermore, the lack of axonal mechanical sensitivity in sympathetic axons rules out channels expressed in these neurons as possible mechano-electrical transducers.