Experimental neurology
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Experimental neurology · Mar 2008
Prevention of paclitaxel-evoked painful peripheral neuropathy by acetyl-L-carnitine: effects on axonal mitochondria, sensory nerve fiber terminal arbors, and cutaneous Langerhans cells.
Prophylactic treatment with acetyl-L-carnitine (ALCAR) prevents the neuropathic pain syndrome that is evoked by the chemotherapeutic agent, paclitaxel. The paclitaxel-evoked pain syndrome is associated with degeneration of the intraepidermal terminal arbors of primary afferent neurons, with the activation of cutaneous Langerhans cells, and with an increased incidence of swollen and vacuolated axonal mitochondria in A-fibers and C-fibers. Previous work suggests that ALCAR is neuroprotective in other nerve injury models and that it improves mitochondrial dysfunction. ⋯ In animals with a confirmed ALCAR effect, we found no evidence of a neuroprotective effect on the paclitaxel-evoked degeneration of sensory terminal arbors or an inhibition of the paclitaxel-evoked activation of Langerhans cells. However, ALCAR treatment completely prevented the paclitaxel-evoked increase in the incidence of swollen and vacuolated C-fiber mitochondria, while having no effect on the paclitaxel-evoked changes in A-fiber mitochondria. Our results suggest that the efficacy of prophylactic ALCAR treatment against the paclitaxel-evoked pain may be related to a protective effect on C-fiber mitochondria.
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Experimental neurology · Mar 2008
Gadofluorine M-enhanced magnetic resonance nerve imaging: comparison between acute inflammatory and chronic degenerative demyelination in rats.
Nerve imaging by magnetic resonance imaging (MRI) is an emerging tool for the diagnostic work-up of patients with PNS disorders. We have recently shown that the experimental MR contrast agent gadofluorine M (Gf, Bayer Schering Pharma AG, Berlin) accumulates in nerves undergoing Wallerian degeneration and in areas of acute focal demyelination allowing in-vivo assessment of nerve pathology. The exact pathomechanism underlying Gf accumulation in peripheral nerve disorders is unknown so far. ⋯ In conclusion, our data show that the novel MR contrast agent Gf, but not Gadolinium (Gd)-DTPA, facilitates detection of ongoing demyelination by MR neurography independent from the underlying pathology. It appears that the extent of Gf enhancement depends on the acuity of demyelination and is probably related to a transient disturbance of the blood-nerve barrier. Clinical development of Gf may help to further improve the sensitivity of nerve lesion assessment by MRI in patients with peripheral neuropathies.
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Experimental neurology · Mar 2008
A flow sensitive alternating inversion recovery (FAIR)-MRI protocol to measure hemispheric cerebral blood flow in a mouse stroke model.
Blood flow imaging is an important tool in cerebrovascular research. Mice are of special interest because of the potential of genetic engineering. Magnetic resonance imaging (MRI) provides three-dimensional noninvasive quantitative methods of cerebral blood flow (CBF) imaging, but these MRI techniques have not yet been validated for mice. ⋯ Using FAIR-MRI, the corresponding average CBFs were 208+/-56 (isoflurane, intact hemisphere, n=7), 84+/-9 (etomidate, intact hemisphere, n=7), 72+/-22 (isoflurane, MCAo hemisphere, n=7) and 48+/-13 (etomidate, MCAo hemisphere, n=7). Regression analysis showed a strong linear correlation between CBF measured with FAIR-MRI and (14)C-IAP autoradiography, and FAIR-MRI overestimated CBF compared to autoradiography. FAIR-MRI provides repetitive quantitative measurements of hemispheric CBF in a mouse model of stroke.