[en] Peripheral neuropathy of the external popliteal ischiadic nerve caused by intraneural cysts is a very rare and peculiar pathological phenomenon compared with diseases associated with extraneural cysts or colliquative phenomena of solid nervous lesions. Two cases of peripheral neuropathy of the external poplitheal ischiadic nerve caused by intra-neural cysts and evaluated with ultrasound, computed tomography and magnetic resonance are described. The diagnostic efficacy of these imaging modalities is also evaluated with particular reference to MR capability to define the morphology of such lesions and their relation-ships to the surrounding structures. It is not yet possible to obtain a correct diagnosis about histopathologic features by means of the imaging techniques currently available. Nevertheless, they provide information about the involvement of the neighboring areas, which are useful indications for possible surgical treatment of the disease. (author). 9 refs.; 2 figs

[en] Complete text of publication follows: Objectives: The parameters that control the variability of response and tolerance to opioid analgesics are not fully understood. Many preclinical studies have highlighted the interaction of morphine and other opioids with the innate immune system of the brain, especially microglial cells. Morphine was shown to promote microglial activation and trigger inflammatory pathways such as that of Toll-like receptor 4 (TLR4), with the release of pro-inflammatory cytokines in the brain. Interestingly, morphine-induced microglial activation was shown to modulate its pain-relieving properties. This suggests that glial modulation may be an underexplored parameter of the variability of response to opioids in patients. The relevance of Translocator protein 18 kDa (TSPO) PET imaging with ¹⁸F-DPA-714, a marker of glial activation, was investigated as a minimally-invasive method to investigate morphine-induced glial activation in vivo. Methods: Five Male Papio anubis baboons (25-30 kg, 8-10 years old) underwent ¹⁸F-DPA-714 PET imaging (226 ± 21 MBq - 120 min dynamic PET acquisition, HR+ Siemens scanner) at baseline and 2 hours after intramuscular morphine injection (1 mg/kg). Brain kinetics and metabolite-corrected input function were measured to estimate ¹⁸F-DPA-714 brain distribution in the whole brain and in 12 brain regions (VT; mL.cm^-3; Logan graphical analysis). Brain VTs obtained in the presence or in the absence of morphine were statistically compared by a paired t-test. Response to morphine administration was characterized by the ratio R of VT after morphine injection over VT before morphine injection. Results: Morphine did not influence the plasma kinetics of ¹⁸F-DPA-714, indicating the absence of peripheral drug-drug interaction between these compounds: parent ¹⁸F-DPA-714 in plasma, measured from 40 to 120 min (elimination phase) were not different between baseline (SUV = 0.06 ± 0.01) and acute morphine conditions (SUV = 0.05 ± 0.01). In morphine-treated animals, ¹⁸F-DPA-714 VT was significantly higher than VT at baseline (18.8 ± 11.8 mL.cm^-3 vs 14.3 ± 8.4 mL.cm^-3, p≤0.05). Regional analysis and ANOVA showed that the response to morphine as measured by R was not significantly different (p≥0.05) between the different brain regions. High differences in the basal distribution of ¹⁸F-DPA-714 were observed among the baboons. We did not identify any parameter (origin, age, nature/number of previous anesthesia or treatments) that could explain this disparity. Interestingly, the response to morphine exposure predominated in animals with a higher baseline distribution. Conclusion: Acute morphine exposure significantly increases the binding of ¹⁸F-DPA-714 to the brain in nonhuman primates. The effect was observed globally across brain regions and predominated in animals with the highest baseline uptake, suggesting that priming parameters still to be identified play a role in controlling the neuroimmune response to morphine. PET imaging using ¹⁸F-DPA-714 is a relevant approach for the minimally-invasive study of the neuroimmune component of morphine pharmacology in vivo

[en] Knockout (KO) animals are useful tools with which to assess the interplay between P-glycoprotein (P-gp; Abcb1) and the breast cancer resistance protein (Bcrp, Abcg2), two major ABC-transporters expressed at the blood-brain barrier (BBB). However, one major drawback of such deficient models is the possible involvement of compensation between transporters. In the present study, P-gp and Bcrp distribution in the brain as well as P-gp expression levels at the BBB were compared between the Bcrp TGEM KO rat model and the wild-type (WT) strain. Therefore, we used confocal microscopy of brain slices and western blot analysis of the isolated brain microvessels forming the BBB. This deficient rat model was used to assess the influence of Bcrp on the brain and peripheral kinetics of its substrate ["1"1C]befloxatone using positron emission tomography (PET). The influence of additional P-gp inhibition was tested using elacridar (GF120918) 2 mg/kg in Bcrp KO rats. The distribution pattern of P-gp in the brain as well as P-gp expression levels at the BBB was similar in Bcrp-deficient and WT rats. Brain and peripheral kinetics of ["1"1C]befloxatone were not influenced by the lack of Bcrp. Neither was the brain uptake of ["1"1C]befloxatone in Bcrp-deficient rats influenced by the inhibition of P-gp. In conclusion, the Bcrp-deficient rat strain, in which we detected no compensatory mechanism or modification of P-gp expression as compared to WT rats, is a suitable model to study Bcrp function separately from that of P-gp at the BBB. However, although selectively transported by BCRP in vitro, our results suggest that ["1"1C]befloxatone PET imaging might not be biased by impaired function of this transporter in vivo. (authors)