Androgen receptor mRNA regulation in adult male and female hamster facial motoneurons: effects of axotomy and exogenous androgens

Testosterone propionate (TP) administration at the time of facial nerve injury in the adult hamster augments the regenerative properties of the injured facial motoneurons (FMN), with the androgen receptor (AR) playing a key role in mediating the actions of TP on facial nerve regeneration. The purpose of the present study was to determine the effects of axotomy on AR mRNA expression in FMN. This was accomplished using in situ hybridization in conjunction with a (35)S-labeled AR riboprobe. Gonadally intact adult male and gonadectomized (gdx) adult female hamsters were subjected to a right facial nerve axotomy, with the left side serving as internal, unoperated control. Half the animals were subcutaneously implanted with a 10-mm TP Silastic capsule, and the other half were sham-implanted. An additional group of nonaxotomized, gonadally intact males was also included. Postaxotomy survival times were 1, 4, and 7 days. At 1 postoperative day 1, there were no effects of axotomy on AR mRNA levels. By postoperative days 4 and 7, axotomy caused a significant decrease in AR mRNA levels in FMN of gonadally intact males, relative to either the contralateral control FMN of the same animals or FMN from the group of gonadally intact males that were not subjected to facial nerve axotomy. There were no significant differences between AR mRNA levels in contralateral control FMN and FMN from the gonadally intact group of nonaxotomized males. TP administration at the time of axotomy had no effect on AR mRNA levels in either the axotomized or contrala(teral control FMN of gonadally intact males, relative to the nonaxotomized, gonadally intact male group. Corroborating our previous work, AR mRNA levels were reduced in the contralateral control FMN of gdx females, relative to the nonaxotomized, gonadally intact male group, with axotomy having no additional effects. The data are discussed in a mechanistic framework suggesting how TP acts to augment facial nerve regeneration.     

Gonadal Steroid Regulation of Growth-Associated Protein GAP-43 mRNA Expression in Axotomized Hamster Facial Motor Neurons

Treatment with testosterone propionate (TP) after nerve injury is known to accelerate both the rate of axonal regeneration and functional recovery from facial paralysis in the adult male hamster. Peripheral nerve injury is also known to increase the expression of a 43 kilodalton growth-associated protein (GAP-43). In the intact brain, GAP-43 expression is affected by gonadal steroids. We thus postulated that steroidal modulation of GAP-43 gene expression may be a component of the neurotrophic action of TP in regenerating neurons. This issue was examined in hamster facial motor neurons (FMN) which contain androgen receptors and which have been shown to respond to exogenous steroids in a number of previous studies. Castrated adult male hamsters were subjected to right facial nerve transection and treated with either TP via subcutaneous hormone capsule implants, or left untreated (no hormone replacement). At post-injury/treatment times of 0.25, 2, 4, 7, and 14 d, the brain stem regions were harvested, cryostat sections were collected through the facial motor nucleus, and in situ hybridization was done using a ³³P-labeled GAP-43 cDNA probe. Quantitative analysis of the autoradiograms by computer assisted grain counting revealed that axotomy produced a dramatic increase in GAP-43 mRNA levels in FMN by 2 d post-axotomy and that this increase remained through 14 d post-injury in both the TP-treated and the untreated group. In the nonhormone-treated group, there was a statistically significant dip in GAP-43 mRNA levels in FMN at 7 d post-operative, relative to 4 d post-operative levels. TP-treatment prevented this transient decline in GAP-43 mRNA levels in axotomized FMN.     

Alterations in Glial Fibrillary Acidic Protein (GFAP) mRNA Levels in the Hamster Facial Motor Nucleus: Effects of Axotomy and Testosterone

Testosterone propionate (TP) administered at the time of facial nerve injury in the hamster accelerates the rate of regeneration. In this study, we tested the hypothesis that the mechanism by which TP augments peripheral nerve regeneration involves regulation of glial fibrillary acidic protein (GFAP) mRNA in the facial motor nucleus. Castrated male hamsters were subjected to right facial nerve transection, with half the animals implanted subcutaneously with Silastic capsules containing exogenous TP and the remainder sham implanted. Postoperative survival times were 0.25, 1, 2, 4, 7, and 14 d. Qualitative/quantitative analyses of both film and emulsion autoradiograms were accomplished. Axotomy, with or without TP, resulted in a dramatic increase in GFAP mRNA levels by 1 d postoperative on the axotomized side, relative to controls. GFAP mRNA levels remained elevated throughout all postoperative times in both the nonhormone- and TP-treated animals. Qualitative examination of the film autoradiograms indicated a generalized decrease in the amount of GFAP mRNA in the control and axotomized nuclei of TP-treated animals when compared to the control and axotomized nuclei, respectively, of nonhormone-treated animals. Statistical comparison of the values obtained for both the film and emulsion autoradiograms confirmed this impression. Thus, while the injury-induced increases in GFAP mRNA expression were not blocked by TP, the overall extent of the increase was significantly tempered by steroid treatment. These data suggest that hormonal modulation of the astrocytic response to peripheral nerve injury may be a contributing factor in the ability of steroids to enhance the regenerative capacities of injured motor neurons.     

Estrogen receptor expression in the facial nucleus of adult hamsters: does axotomy recapitulate development?

Testosterone propionate (TP) augments hamster facial motoneuron regeneration following axonal injury by an androgen-mediated mechanism. Although many of the trophic properties of TP are androgenic, TP can be metabolized to estradiol (E). We have recently shown that E administered in supraphysiological doses can also enhance facial nerve regeneration. The mechanism by which E alters nerve regeneration is unknown. The recent discovery of transient estrogen receptor (ER) expression in the developing rat facial motor nucleus (FMN), coupled with the concept that regeneration may recapitulate development, has led to the hypothesis that facial nerve injury may transiently induce expression of ER in the adult hamster FMN or one of its chief afferents, the principal nucleus of the trigeminal nerve (Nu5). In the present study, this hypothesis was tested using steroid hormone autoradiographic procedures. The right facial nerve was injured in castrated or castrated plus TP adult hamsters. A gonadally intact, nonaxtomized group of hamsters was also included to examine constitutive expression of ER in the FMN or Nu5. The paraventricular nucleus of the hypothalamus (PVN; positive control), FMN, and Nu5, were qualitatively and quantitatively examined for the presence of ER. As expected, ER were present in the PVN-positive control in all groups. ER were neither present nor induced with facial nerve injury or TP administration in either the FMN or Nu5. Alternate mechanisms by which E enhancement of facial nerve regeneration without ER might be explained are discussed.     

Gonadal steroid preservation of central synaptic input to hamster facial motoneurons following peripheral axotomy

In recent work, we have demonstrated that testosterone propionate accelerates recovery from facial nerve injury in the adult male hamster. Central synaptic stripping following peripheral motor neuron damage is a well-established component of the injury response. Gonadal steroids regulate synaptogenesis in the normal nervous system. In this study, we tested the hypothesis that testosterone propionate administration at the time of facial nerve transection alters the synaptic connectivity of injured facial motoneurons. Adult hamsters were subjected to right facial nerve transection at the level of the stylomastoid foramen. Half the animals received subcutaneous implants of testosterone propionate; the other half were sham implanted. At 5 days postoperative, the animals were killed by intracardiac perfusion-fixation, and the control and axotomized facial nuclear groups from the brainstems of nonhormone- and testosterone propionate-treated animals processed for routine transmission electron microscopy. Quantiative analysis of the synaptic ratio (percent somal membrane covered by synaptic profiles) and the average length of axosomatic synapses was accomplished. The results indicate that axotomy alone resulted in an 81% reduction in the synaptic ratio and a 26% decrease in the average synaptic length of axosomatic synapses. Exposure to testosterone propionate from the time of facial nerve transection resulted in only a 48% reduction in the synaptic ratio and a 16% decrease in the average synaptic length of axosomatic synapses following injury. Thus, testosterone propionate significantly attenuated the amount of synaptic stripping that occurred at 5 days postoperative and the decrease in average length of the remaining synapses as well. It is concluded that gonadal steroids modulate central synaptic plasticity following peripheral nerve injury. The results are discussed in light of our recent findings of steroidal effects on the central astrocyctic response to facial nerve injury as well.     

Facial Nerve Axotomy in Mice: A Model to Study Motoneuron Response to Injury

The goal of this surgical protocol is to expose the facial nerve, which innervates the facial musculature, at its exit from the stylomastoid foramen and either cut or crush it to induce peripheral nerve injury. Advantages of this surgery are its simplicity, high reproducibility, and the lack of effect on vital functions or mobility from the subsequent facial paralysis, thus resulting in a relatively mild surgical outcome compared to other nerve injury models. A major advantage of using a cranial nerve injury model is that the motoneurons reside in a relatively homogenous population in the facial motor nucleus in the pons, simplifying the study of the motoneuron cell bodies. Because of the symmetrical nature of facial nerve innervation and the lack of crosstalk between the facial motor nuclei, the operation can be performed unilaterally with the unaxotomized side serving as a paired internal control. A variety of analyses can be performed postoperatively to assess the physiologic response, details of which are beyond the scope of this article. For example, recovery of muscle function can serve as a behavioral marker for reinnervation, or the motoneurons can be quantified to measure cell survival. Additionally, the motoneurons can be accurately captured using laser microdissection for molecular analysis. Because the facial nerve axotomy is minimally invasive and well tolerated, it can be utilized on a wide variety of genetically modified mice. Also, this surgery model can be used to analyze the effectiveness of peripheral nerve injury treatments. Facial nerve injury provides a means for investigating not only motoneurons, but also the responses of the central and peripheral glial microenvironment, immune system, and target musculature. The facial nerve injury model is a widely accepted peripheral nerve injury model that serves as a powerful tool for studying nerve injury and regeneration.     

家兔迟发性面瘫模型建立及药物干预研究

目的:优化迟发性面瘫的建模方法,并对药物的神经保护作用进行观察。方法:家兔48只共96侧面神经,分A、B、C、D 4个实验组,以一侧面神经进行实验处理,另一侧为自身对照。A组:直视下钳夹损伤桥池段面神经;B组:直视下向桥小脑角注射动脉血,以诱导血管痉挛;C组:处理因素=A组+B组;D组:在C组基础上,应用药物(强的松+丹参+维生素B1+维生素B12)干预。观察家兔面瘫,并做面神经病理切片,比较各组间迟发性面瘫发生率、面瘫持续时间及预后。结果:面瘫发生情况:A组6只家兔(6/11,54.5%)出现迟发性面瘫;平均面瘫持续时间为13.2天。B组有2只(2/12,16.7%)出现迟发性面瘫,平均持续8天。C组6只(6/12,50%)家兔出现迟发性面瘫,平均持续14.3天。D组4只(4/12,33.33%)出现迟发性面瘫,平均持续6天。所有自身对照侧均无面瘫发生。病理:各组均见神经纤维水肿;A、C两组呈高度水肿改变,神经束周围结构紊乱;B组见神经内血管细小,而水肿较A、C两组轻微;D组呈轻度水肿改变。结论:C组出现迟发性面瘫几率高,是较好的模型;联合应用强的松、丹参、维生素B1、维生素B12虽不能防止迟发性面瘫发生,但可使迟发性面瘫病程明显缩短。     

家兔迟发性面瘫模型建立及药物干预研究

目的：优化迟发性面瘫的建模方法,并对药物的神经保护作用进行观察。方法：家兔48只共96侧面神经,分A、B、C、D4个实验组,以一侧面神经进行实验处理,另一侧为自身对照。A组：直视下钳夹损伤桥池段面神经;B组：直视下向桥小脑角注射动脉血,以诱导血管痉挛;C组：处理因素=A组＋B组;D组：在C组基础上,应用药物（强的松＋丹参＋维生素BI＋维生素B12）干预。观察家兔面瘫,并做面神经病理切片,比较各组间迟发性面瘫发生率、面瘫持续时间及预后。结果：面瘫发生情况：A组6只家兔（6／11,54．5％）出现迟发性面瘫;平均面瘫持续时间为13．2天。B组有2只（2／12,16．7％）出现迟发性面瘫,平均持续8天。C组6只（6／12,50％）家兔出现迟发性面瘫,平均持续14.3天。D组4只（4／12,33．33％）出现迟发性面瘫,平均持续6天。所有自身对照侧均无面瘫发生。病理：各组均见神经纤维水肿;A、c两组呈高度水肿改变,神经束周围结构紊乱;B组见神经内血管细小,而水肿较A、C两组轻微;D组呈轻度水肿改变。结论：C组出现迟发性面瘫几率高,是较好的模型;联合应用强的松、丹参、维生素B1、维生素B12虽不能防止迟发性面瘫发生,但可使迟发性面瘫病程明显缩短。     

Effects of facial nerve injury on mouse motoneurons lacking the p75 low-affinity neurotrophin receptor

When motoneuron axons in peripheral nerves are injured, the expression of the p75 low-affinity neurotrophin receptor (p75) increases in their cell bodies and axons, as well as in the Schwann cells undergoing Wallerian degeneration in the distal excised nerve segment. To understand the role of p75 in the events following nerve injury, we have examined the survival and regeneration of motoneurons in mice lacking the p75 receptor. In adult p75 (−/−) mice, functional recovery of whiskers movement following a facial nerve crush occurred slightly earlier than in p75 (+/+) mice, and some recovery of function over a 25-day interval following a nerve cut occurred more frequently in p75 (−/−) mice. Motoneuron profile numbers were slightly reduced in p75 (−/−) mice, and there were correspondingly fewer axons in the facial nerve. At 25 days following axotomy, profile survival in the adult p75 (−/−) mice was significantly improved compared to p75 (+/+) mice (mean 85% ± standard error of the mean 3%, n = 11 vs. 67 ± 5%, n = 11 in CD-1 mice and 68.0 ± 4%, n = 6 in balb/c mice), and significantly more regenerating axons were present in the distal facial nerve. After axotomy on postnatal day 1, there was almost total loss of motoneuron profiles in the lateral facial nucleus in p75 (+/+) mice (1.7 ± 0.3% remained, n = 5), while significantly more survived in p75 (−/−) mice (17 ± 2.5%, n = 6) . We conclude that expression of p75 in motoneurons or Schwann cells following facial nerve injury is not necessary for motoneuron survival or prompt regeneration of their axons; rather, p75 may increase their risk of dying. © 1998 John Wiley & Sons, Inc. J Neurobiol 34: 1–9, 1998     

Neuronal c-Jun is required for successful axonal regeneration, but the effects of phosphorylation of its N-terminus are moderate

Although neural c-Jun is essential for successful peripheral nerve regeneration, the cellular basis of this effect and the impact of c-Jun activation are incompletely understood. In the current study, we explored the effects of neuron-selective c-Jun deletion, substitution of serine 63 and 73 phosphoacceptor sites with non-phosphorylatable alanine, and deletion of Jun N-terminal kinases 1, 2 and 3 in mouse facial nerve regeneration. Removal of the floxed c-jun gene in facial motoneurons using cre recombinase under control of a neuron-specific synapsin promoter (junΔS) abolished basal and injury-induced neuronal c-Jun immunoreactivity, as well as most of the molecular responses following facial axotomy. Absence of neuronal Jun reduced the speed of axonal regeneration following crush, and prevented most cut axons from reconnecting to their target, significantly reducing functional recovery. Despite blocking cell death, this was associated with a large number of shrunken neurons. Finally, junΔS mutants also had diminished astrocyte and microglial activation and T-cell influx, suggesting that these non-neuronal responses depend on the release of Jun-dependent signals from neighboring injured motoneurons. The effects of substituting serine 63 and 73 phosphoacceptor sites (junAA), or of global deletion of individual kinases responsible for N-terminal c-Jun phosphorylation were mild. junAA mutants showed decrease in neuronal cell size, a moderate reduction in post-axotomy CD44 levels and slightly increased astrogliosis. Deletion of Jun N-terminal kinase (JNK)1 or JNK3 showed delayed functional recovery; deletion of JNK3 also interfered with T-cell influx, and reduced CD44 levels. Deletion of JNK2 had no effect. Thus, neuronal c-Jun is needed in regeneration, but JNK phosphorylation of the N-terminus mostly appears to not be required for its function.     

Axonal Regeneration after Sciatic Nerve Lesion Is Delayed but Complete in GFAP- and Vimentin-Deficient Mice

Peripheral axotomy of motoneurons triggers Wallerian degeneration of injured axons distal to the lesion, followed by axon regeneration. Centrally, axotomy induces loss of synapses (synaptic stripping) from the surface of lesioned motoneurons in the spinal cord. At the lesion site, reactive Schwann cells provide trophic support and guidance for outgrowing axons. The mechanisms of synaptic stripping remain elusive, but reactive astrocytes and microglia appear to be important in this process. We studied axonal regeneration and synaptic stripping of motoneurons after a sciatic nerve lesion in mice lacking the intermediate filament (nanofilament) proteins glial fibrillary acidic protein (GFAP) and vimentin, which are upregulated in reactive astrocytes and Schwann cells. Seven days after sciatic nerve transection, ultrastructural analysis of synaptic density on the somata of injured motoneurons revealed more remaining boutons covering injured somata in GFAP^–/–Vim^–/– mice. After sciatic nerve crush in GFAP^–/–Vim^–/– mice, the fraction of reinnervated motor endplates on muscle fibers of the gastrocnemius muscle was reduced 13 days after the injury, and axonal regeneration and functional recovery were delayed but complete. Thus, the absence of GFAP and vimentin in glial cells does not seem to affect the outcome after peripheral motoneuron injury but may have an important effect on the response dynamics.     

Diphenylpiperazines enhance regeneration after facial nerve injury

Immature rat facial motoneurons are very sensitive to injury with nearly 80% dying during the first week after axotomy. This motoneuron death is apoptotic, similar to that induced in neurons after tropic factor withdrawal. The diphenylpiperazines, flunarizine and cinnarizine, protect dorsal root ganglion neurons from death after withdrawal of trophic support, i.e., nerve growth factor withdrawal, in vitro. Similarly, the monoamine oxidase inhibitor, deprenyl, promotes survival of facial motoneurons after axotomy. These pharmacological agents were assessed both alone and in combination for their ability to prevent death in non-nerve growth factor dependent CNS motoneurons after facial nerve axotomy in newborn rats. Long-term experiments were done with the diphenylpiperazines to evaluate potential enhancement of regeneration. Facial nerve transection resulted in 78% neuronal loss in the injured compared with the contralateral, uninjured nucleus. Systemic administration of diphenylpiperazines for 1 week after facial nerve transection doubled the number of surviving motoneurons from 23% to 47%. Similar results were obtained with deprenyl. Combinations of diphenylpiperazines and deprenyl provide a similar degree of neuronal protection 1 week after injury as that obtained by either agent alone. We assessed the ability of diphenylpiperazines to protect facial motoneurons from death over a prolonged period and enhance subsequent regeneration. Motor neuron counts in rats treated with diphenylpiperazines for 1 month after injury and assessed 2 months later demonstrated long-term enhancement of neuronal protection with an increase of 45% in the number of horseradish peroxidase-labelled motoneurons. The diphenylpiperazines group had ～80% more regenerated myelinated axons in the distal facial nerve than the control group. Thus, diphenylpiperazine treatment during the first month after injury provides long-term protection of non-nerve growth factor dependent CNS motoneurons with subsequent potentiation of long-term facial nerve regeneration.     

Induction of Urokinase-Type Plasminogen Activator in Rat Facial Nucleus by Axotomy of the Facial Nerve

Abstract: The response of plasminogen activator activity in the CNS to peripheral nerve axotomy was examined in vivo. After transection of the rat facial nerve, a transient increase in plasminogen activator activity was observed in the facial nucleus on the operated side with maximal activity 3–5 days after lesion. This activity was inhibited by the urokinase-specific inhibitor amiloride but not by antibodies against tissue plasminogen activator. The molecular mass of the induced form of plasminogen activator was estimated to be ∼48 kDa. An in vitro assay of plasminogen hydrolysis also demonstrated an increase in amiloride-sensitive plasminogen activator activity in facial nerve extracts following facial nerve axotomy. These data indicate that the plasminogen activator activity induced in the facial nucleus following axotomy of facial motoneurons is of the urokinase type. It is suggested that the urokinase-type plasminogen activator might play a role in the events accompanying injury and regeneration in the facial nucleus following motoneuron lesion.     

Secretion of EGF-like domain of heregulinβ promotes axonal growth and functional recovery of injured sciatic nerve

Neuregulin 1 (NRG1) and epidermal growth factor receptor (ErbB) signaling pathways control Schwann cells during axonal regeneration in an injured peripheral nervous system. We investigated whether a persistent supply of recombinant NRG1 to the injury site could improve axonal growth and recovery of sensory and motor functions in rats during nerve regeneration. We generated a recombinant adenovirus expressing a secreted form of EGF-like domain from Heregulinβ (sHRGβE-Ad). This virus, sHRGβE-Ad allowed for the secretion of 30-50 ng of small sHRGβE peptides per 10^7–8 virus particle outside cells and was able to phosphorylate ErbB receptors. Transduction of the concentrated sHRGβE-Ad into an axotomy model of sciatic nerve damage caused an effective promotion of nerve regeneration, as shown by histological features of the axons and Schwann cells, as well as increased expression of neurofilaments, GAP43 and S100 in the distal stump of the injury site. This result is consistent with longer axon lengths and thicker calibers observed in the sHRGβE-Ad treated animals. Furthermore, sensory and motor functions were significantly improved in sHRGβE-Ad treated animals when evaluated by a behavioral test. These results suggest a therapeutic potential for sHRGβE-Ad in treatment of peripheral nerve injury.     

微血管减压术治疗面肌痉挛术后相关并发症的临床分析

目的:总结面肌痉挛患者的术后并发症的发生情况并分析其原因。方法:回顾性分析了1548名在我院行微血管减压术治疗面肌痉挛的患者的临床资料,所有患者接受电话随访或者门诊随访,随访时间均超过2年,总结其临床疗效及术后并发症的发生情况。结果:微血管减压术后痊愈率及明显缓解率分别为92.5%及4.2%。249名(16.09%)患者出现不同的并发症,其中最常见的并发症为面瘫及术后手术区域皮肤感觉障碍,无死亡及重大并发症患者。听力损害发生率为3.5%。其他并发症包括脑脊液漏、后组颅神经损伤、外展神经损伤、颅内出血等。结论:微血管减压术是治疗面肌痉挛的安全有效操作,以手术区域感觉障碍及迟发性面瘫是主要的并发症,持久性的或者严重的并发症比较少见。     

Exacerbation of facial motoneuron loss after facial nerve axotomy in CCR3-deficient mice

We have previously demonstrated a neuroprotective mechanism of FMN (facial motoneuron) survival after facial nerve axotomy that is dependent on CD4⁺ Th2 cell interaction with peripheral antigen-presenting cells, as well as CNS (central nervous system)-resident microglia. PACAP (pituitary adenylate cyclase-activating polypeptide) is expressed by injured FMN and increases Th2-associated chemokine expression in cultured murine microglia. Collectively, these results suggest a model involving CD4⁺ Th2 cell migration to the facial motor nucleus after injury via microglial expression of Th2-associated chemokines. However, to respond to Th2-associated chemokines, Th2 cells must express the appropriate Th2-associated chemokine receptors. In the present study, we tested the hypothesis that Th2-associated chemokine receptors increase in the facial motor nucleus after facial nerve axotomy at timepoints consistent with significant T-cell infiltration. Microarray analysis of Th2-associated chemokine receptors was followed up with real-time PCR for CCR3, which indicated that facial nerve injury increases CCR3 mRNA levels in mouse facial motor nucleus. Unexpectedly, quantitative- and co-immunofluorescence revealed increased CCR3 expression localizing to FMN in the facial motor nucleus after facial nerve axotomy. Compared with WT (wild-type), a significant decrease in FMN survival 4 weeks after axotomy was observed in CCR3^−/− mice. Additionally, compared with WT, a significant decrease in FMN survival 4 weeks after axotomy was observed in Rag2^−/− (recombination activating gene-2-deficient) mice adoptively transferred CD4⁺ T-cells isolated from CCR3^−/− mice, but not in CCR3^−/− mice adoptively transferred CD4⁺ T-cells derived from WT mice. These results provide a basis for further investigation into the co-operation between CD4⁺ T-cell- and CCR3-mediated neuroprotection after FMN injury.     

Selective myectomy for postparetic facial synkinesis

Synkinetic movements are secondary to facial palsy because they appear like a late sequela to spontaneously healing facial nerve injury. They are produced by an involuntary contraction of a muscle group simultaneous with contraction of other homologous muscle groups. The disorderly regeneration of severed axons is responsible for these movements. According to the Lippschitz theory, the regenerating nerve fibers sprout into the wrong peripheral branches. Between 1975 and 1986, 71 patients with facial paralysis were evaluated. Spontaneous recovery from the facial paralysis occurred in 28 of these patients; 14 (50 percent) developed synkinetic movements, and surgical treatment was sought by only 6 patients. In all patients, the lesion of the facial nerve was in the trunk, proximal to the principal ramification. The most frequent clinical finding was simultaneous activation between the orbicularis oculi and the elevators of the corner of the mouth (12 patients) or the elevators of the upper lip (2 patients). In 8 patients, in whom the slight synkinesis was not noticed by the patients, surgical correction was not necessary, but in the other 6 patients with severe aesthetic disturbances, surgical treatment for "disconnection" of the wrong impulses was realized. I obtained this "disconnection" through resection of the involved perioral muscle groups instead of paralysis of the orbicularis oculi. Follow-up of the 6 patients operated with the surgical treatment proposed herein for between 4 and 8 years has shown good aesthetic results without functional or aesthetic sequelae.     

骨髓间充质干细胞经BDNF基因修饰后移植治疗大鼠半横断脊髓损伤的电生理研究

目的采用电生理的研究方法,观察脑源性神经营养因子(BDNF)基因修饰的骨髓间充质干细胞对脊髓损伤的修复作用。方法随机将大鼠分成3组:空白组10只(只切除椎板,暴露脊髓硬脊膜);SCI组10只;SCI术后细胞移植组10只;从以上三组大鼠随机抽取8只于细胞移植后1 d、7 d、14 d、21 d、30 d、60 d进行SEP(皮层体感诱发电位)、MEP(运动诱发电位)等电生理检测技术,并观察大鼠的运动评分恢复程度。结果细胞移植4d后,大鼠饮食和活动开始增加;后肢变化过程如下:损伤后1~4 d损伤侧后肢迟缓性瘫痪,拖地行走,损伤对侧后肢由损伤初期的运动减弱逐渐恢复,损伤后5~9 d损伤侧后肢痉挛性瘫痪;10~14 d损伤侧下肢恢复少量活动,损伤对侧后肢恢复至较损伤前稍弱的状态;15~21 d损伤侧后肢活动能力较之前有明显改善,至30 d损伤侧后肢活动能力及肌张力恢复程度最明显,30 d以后无更明显改善。免疫组化发现损伤处诱导标记的骨髓间充质干细胞存活,行为学观察发现细胞移植改善了损伤大鼠运动能力。结论骨髓间充质干细胞经BDNF基因修饰后可以促进脊髓损伤大鼠的神经再生及部分传导功能恢复。     

Immediate recovery from spinal cord injury through molecular repair of nerve membranes with polyethylene glycol.

A brief application of the hydrophilic polymer polyethylene glycol (PEG) swiftly repairs nerve membrane damage associated with severe spinal cord injury in adult guinea pigs. A 2 min application of PEG to a standardized compression injury to the cord immediately reversed the loss of nerve impulse conduction through the injury in all treated animals while nerve impulse conduction remained absent in all sham-treated guinea pigs. Physiological recovery was associated with a significant recovery of a quantifiable spinal cord dependent behavior in only PEG-treated animals. The application of PEG could be delayed for approximately 8 h without adversely affecting physiological and behavioral recovery which continued to improve for up to 1 month after PEG treatment.