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Background: In facial reanimation surgery, higher donor facial nerve axonal load yields a superior outcome. Nerves supplying the zygomaticus major muscle are primary donors for the grafting procedure; however, their topography has not been studied in detail. This study identified potential donor nerves by quantifying axon loads of the zygomaticus major muscle through histological analysis of cadaveric specimens. Materials and Methods: Forty-three hemifaces from 26 fresh human cadavers were studied. Branching patterns of nerves were classified according to their shapes. All branches of interest were sectioned and stained for an axon count. The potential donors were mapped into each tributary of nerves supplying the zygomaticus major. Results: Branching patterns were categorized into five types: Y-type (28%), X-type (28%), H-type (19%), E-type (14%), and F-type (11%). The mean number of axons in the most superiorly and proximally located main branches was 1387.33 ± 406.59 in Y-type, 1021.42 ± 187.79 in X-type, 1222.75 ± 193.82 in H-type, 1496.17 ± 364.567 in E-type, and 1353.40 ± 256.07 in F-type (P > 0.05). A topographic relation between facial nerves supplying the zygomaticus major muscle and their mean axonal load was illustrated. The zygomatic/buccal branches were found within 5 mm from Zuker's point in 100% of X-, Y-, H-, and E-type and 75% of F-type specimens. Conclusions: Most proximal facial nerve branches supplying the zygomaticus major, arising at the anterior border of a parotid gland, contained over 900 axons in all five branching types. The primary subbranches may be used in selected cases if donor weakness is a concern. Further, our study provides evidence that demonstrates the precision of Zuker's point.

Peripheral neuropathy is one of the major side effects of cisplatin; however, effective treatments are lacking. Curcumin is a polyphenol found in the root of Curcuma longa and has been shown neuroprotective against several neurological diseases. Nevertheless, its effects on cisplatin neuropathy remain unclear. This study aimed to clarify this issue by inducing neuropathy in the rats with intraperitoneal injection of cisplatin 2 mg/kg twice a week for 5 consecutive weeks. Curcumin 200 mg/kg/day was given by gavage to a group of cisplatin-treated rats during these five weeks. The results showed that cisplatin induced thermal hypoalgesia in the 5(th) week which could be prevented by curcumin. In the 5(th) and 8(th) weeks, sciatic motor nerve conduction velocity was reduced in the cisplatin compared with the control groups. Curcumin significantly attenuated this deficit. Morphometric analysis of L4 dorsal root ganglia from the cisplatin group revealed nuclear and nucleolar atrophy including loss of neurons in the 8(th) week. These alterations were significantly blocked by curcumin. Moreover, curcumin also ameliorated the reduced myelin thickness in the sciatic nerve of cisplatin-treated rats. Taken together, our findings suggest the favorable effects of curcumin on both functional and structural abnormalities in cisplatin neuropathy. Future studies are needed to clarify the exact underlying mechanisms.

p38 member of mitogen-activated protein kinase (MAPK) family has been shown to participate in neuropathic pain and axonal regeneration after nerve injury. However, its role in axotomy-induced neuronal apoptosis remains unclear. This study was aimed to examine p38 phosphorylation in the dorsal root ganglia (DRG) and its role in DRG neuronal loss after axotomy.Left sciatic nerve transection was performed in all rats. For the temporal study of p38 phosphorylation, the rats were sacrificed at 1 day, 2 weeks, and 2 months after injury. In the second experiment, the rats were divided into control and inhibitor groups receiving vehicle and p38 inhibitor (SB203580, 200 μg/kg/day intraperitoneally once daily), respectively, for 2 weeks.The p38 phosphorylation was increased in L4/5 DRG at 2 weeks after transection. Immunoreactivity of phospho-p38 was mainly observed in the cytoplasm of small neurons with additional nuclear localization in the axotomized neurons at 2 weeks. SB203580 could reduce the phosphorylation of p38 and its substrate, ATF2, including the upregulation of total caspase-3 expression in the DRG. Moreover, count of L4/5 DRG neurons revealed significantly decreased cell loss in the inhibitor than control groups (17·4% versus 32·5%).These data suggest the role of p38 in sensory neuronal loss after nerve transection. Future studies should be done to confirm the apoptotic role of p38 in this condition.

Activation of extracellular signal-regulated protein kinase (ERK), a member of the mitogen-activated protein kinase family, has been shown to mediate neurite outgrowth-promoting effects of various neurotrophic factors in vitro. Moreover, in vivo, ERK is activated in the primary sensory neurons and associated glial cells after nerve injury. However, the precise role of ERK in nerve regeneration remains unclear.This work was aimed to investigate the effects of ERK inhibition on axonal regeneration and neuronal loss after axotomy.Unilateral sciatic nerve crush was performed, and inhibition of ERK was achieved by intraperitoneal injection of 300 microg kg(-1) day(-1) of u0126 for 2 weeks in the inhibitor group. For the control group, only the vehicle was given with the same schedule.ERK was activated in the crushed sciatic nerve, and this was significantly reduced by the inhibitor. In contrast, there was no activation of ERK in the L4/L5 spinal ganglia. Morphological analysis revealed the similar extent of neuronal loss in the two groups. In addition, the mean regeneration distance in the inhibitor group was lower than that of the control group.These results suggest the crucial role of ERK in nerve regeneration but not sensory neuronal loss after trauma.

Morphometric analysis of nerve biopsy provides data of structural changes that are essential for early detection of peripheral neuropathy. Because of the laborious work associated with the total fiber quantification, various sampling methods have been introduced with controversial accuracy. Three-window sampling technique has been recently proposed to provide the accurate morphometric data of normal human sural nerve. However, its application in the diseased nerve has not been validated. This study, therefore, compared the morphometric data of nerve biopsies from 12 patients with various neuropathies obtained using this sampling method and those obtained by total fiber analysis. Total number, density, and diameter of myelinated fibers including myelin thickness and g ratio were analyzed. Intraclass correlation coefficients ranging from 0.95 to 0.99 indicate the high agreement between the data derived from the two methods in these parameters. This finding suggests the accuracy of the three-window sampling technique in the morphometric study of nerve with pathological alterations. Microsc. Res. Tech., 2008. © 2008 Wiley-Liss, Inc.

Cisplatin is used as an anti-neoplastic agent against several cancers. Neuropathy is one of its major side effects that contributes to patients' intolerance to the standard regimen. Sex-related differences have been reported in nerve injury and neuropathies. However, there has been no study on cisplatin regarding this issue.Compare various abnormalities in cisplatin neuropathy between sexes.Two mg/kg of cisplatin was administered intraperitoneally twice a week for five consecutive weeks. Body weight, heat latency of hind paw and sciatic motor nerve conduction velocity (MNCV), pathological alterations in the sciatic nerve and dorsal root ganglion (DRG) including the level of NGF in the sciatic nerve were examined. Untreated rats of both sexes were used as controls.Weight loss, prolonged heat latency, and slow MNCV in the treated rats of both sexes with higher severity in males were showed. Furthermore, reduction in myelinated fiber diameter, myelin thickness, and myelinated fiber density was more severe in females, whereas, atrophy of neuronal cell body, nucleus, and nucleolus was more striking in males. The decreased level of NGF was similar between sexes.These data suggest the differences in various aspects of cisplatin neurotoxicity between sexes. However, future studies are needed to verify this issue in a clinical condition and clarify the underlying mechanisms.

Paclitaxel, an anti-neoplastic agent effective against several solid tumors, has several side effects including peripheral neuropathy. So far, there are no effective treatments for this complication. Monosialic acid ganglioside (GM1) has been shown to protect neurons against injuries and degeneration. However, its efficacy in the treatment of paclitaxel-induced neuropathy has not been verified.To evaluate the effect of porcine GM1 on neurophysiological abnormalities in rats receiving paclitaxel.Fifty-four Wistar rats were divided into control, vehicle for paclitaxel (Cremophor EL), paclitaxel, and paclitaxel + GM1 groups. Paclitaxel 16 mg/kg/week for five consecutive weeks was given intraperitoneally. Treatment with 30 mg/kg 5 days per week of GM1 was started 3 days prior to the first dose and continued until 3 days after the last dose of paclitaxel. Tail and hind paw thermal thresholds including tail motor nerve conduction velocity (MNCV) were measured prior to and after the start of treatments. Histopathology of the sciatic nerve was also examined.Paclitaxel alone induced thermal hypoalgesia and reduced tail MNCV Less severe abnormalities were also found with the vehicle. GM1 appeared to prevent the development of hypoalgesia and ameliorated the decreased MNCV without any evidence of Guillain-Barre Syndrome. Mild endoneurial edema and axonal degeneration in the sciatic nerve sections were seen in paclitaxel treated rats. Microtubule accumulation and activated Schwann cell were also presented in the paclitaxel treated groups.These data suggest that porcine GM1 may be useful in the prevention and treatment of paclitaxel-induced neuropathy. However the adverse effect of Cremophor EL should be of concern.

Morphometry has an important role in the interpretation of sural nerve biopsies. It is used for early detection of structural abnormalities in peripheral neuropathies. This application requires a comparison with data of normal population. However, most data in the literature were of Western subjects with a small number of samples. In this study the authors reported the morphometric data of sural nerve harvested within 24 hours after death from 78 Thai subjects without known causes of neuropathy. The samples were transversely sectioned and analyzed for the number and area of fascicles, the total number of myelinated axons, myelinated fiber diameter; myelinated axon diameter, myelin sheath thickness, g ratio and myelinated axon density. Results were discordant in some measurement parameters compared to previous reports. These data are valuable for the early recognition of peripheral nerve diseases from biopsied sural nerve of Thai subjects.

Background Activation of extracellular signal-regulated protein kinase (ERK), a member of mitogen-activated protein kinase (MAPK) family, has been proposed to mediate neurite outgrowth-promoting effects of several neurotrophic factors in vitro. However, the precise activity of ERK during axonal regeneration in vivo remains unclear. Peripheral axotomy has been shown to activate ERK in the cell bodies of primary afferent neurons and associated satellite cells. Nevertheless, whether ERK is also activated in the axons and surrounded Schwann cells which also play a key role in the regeneration process has not been clarified. Results Phosphorylation of ERK in the sciatic nerve in several time-points after crush injury has been examined. Higher phosphorylation of ERK was observed in the proximal and distal nerve stumps compared to the contralateral intact nerve from one day to one month after crush. The activation of ERK was mainly localized in the axons of the proximal segments. In the distal segments, however, active ERK was predominantly found in Schwann cells forming Bungner's bands. Conclusion The findings indicate that ERK is activated in both the proximal and distal nerve stumps following nerve injury. The role of activated ERK in Wallerian degeneration and subsequent regeneration in vivo remains to be elucidated.