BACKGROUND： Erythropoietin and recombinant human erythropoietin （rhEPO） inhibit apoptosis of motor neurons caused by spinal cord injury and brain damage in rats. However, it still remains to be shown whether rhEPO ...BACKGROUND： Erythropoietin and recombinant human erythropoietin （rhEPO） inhibit apoptosis of motor neurons caused by spinal cord injury and brain damage in rats. However, it still remains to be shown whether rhEPO can protect facial motoneurons （FMNs） as Well. OBJECTIVE： To test the neuroprotective effects of rhEPO on injured VMNs, as well as the influence on Caspase-3 expression. DESIGN, TIME AND SETTING： Randomized, controlled, animal experiment. This study was performed at the Central Laboratory of Basic Medical College, Chongqing Medical University from January to October 2007. MATERIALS： Seventy-five female SD rats, weighing 210-230 g. rhEPO injection was provided by Sansheng pharmaceuticals company, Shenyang City, Liaoning Province, China, and the License number was HMLN S20010001. METHODS： A total of 75 female rats were randomly divided into rhEPO treatment, control, and sham operation groups, with 25 rats in each group. Rat models of facial nerve injury were established in the rhEPO treatment group and the control group by crushing the main trunk of the left facial nerve. Surgical microscopic observation of the facial nerve damage displayed perineurial disruption. The left stylomastoid foramen of the sham operation group were only exposed, but without nerve injury. The rhEPO treatment group was treated with rhEPO （5 000 U/kg, i.p.） once following injury and once a day for two weeks. The control and sham operation groups were treated with the same dose of normal saline （i.p.）, once following injury and once a day for two weeks. MAIN OUTCOME MEASURES： Rats were sacrificed 3, 7, 14, 21, and 28 days after injury, FMN survival after facial nerve injury was analyzed by Toluidine blue staining, and then survival ratios （L/R） were calculated. The number of apoptotic profiles in the injured FMNs were evaluated by TUNEL staining. Expression of Caspase-3 in the facial nucleus was detected by immunohistochemistry methods. RESULTS： A total of 75 rats were included in the final analysis. FMN survival ratios, both in rhEPO treatment group and control group, decreased gradually between seven and 28 days; however, FMN survival ratios were significantly greater in the rhEPO treatment group compared to the control group （P 〈 0.05）. No TUNEL-positive cells were observed three days after injury in the rhEPO treatment and control groups; however, by seven days after injury, apoptotic cells were observed and peaked by 14 days in the control group. Between seven and 21 days, apoptotic cell numbers were significantly lower in the rhEPO treatment group compared to the control group （P 〈 0.05）. The expression of Caspase-3 increased three days after injury and peaked at 14 days in the control group. Nevertheless, Caspase-3 expression was significantly lower in the rhEPO treatment group compared to the control group at each time point （P 〈 0.05）. CONCLUSION： Treatment with rhEPO can effectively protect facial motoneurons by reducing expression of Caspase-3 and inhibiting apoptosis.展开更多
The intricate anatomy and physiology of cranial nerves have inspired clinicians and scientists to study their roles in the nervous system. Damage to motor cranial nerves may result from a variety of organic or iatroge...The intricate anatomy and physiology of cranial nerves have inspired clinicians and scientists to study their roles in the nervous system. Damage to motor cranial nerves may result from a variety of organic or iatrogenic insults and causes devastating functional impairment and disfigurement. Surgical innovations directed towards restoring function to injured motor cranial nerves and their associated organs have evolved to include nerve repair, grafting, substitution, and muscle transposition. In parallel with this progress, research on tissue-engineered constructs, development of bioelectrical interfaces, and modulation of the regenerative milieu through cellular, immunomodulatory, or neurotrophic mechanisms has proliferated to enhance the available repertoire of clinically applicable reconstructive options. Despite these advances, patients continue to suffer from functional limitations relating to inadequate cranial nerve regeneration, aberrant reinnervation, or incomplete recovery of neuromuscular function. These shortfalls have profound quality of life ramifications and provide an impetus to further elucidate mechanisms underlying cranial nerve denervation and to improve repair. In this review, we summarize the literature on reconstruction and regeneration of motor cranial nerves following various injury patterns. We focus on seven cranial nerves with predominantly efferent functions and highlight shared patterns of injuries and clinical manifestations. We also present an overview of the existing reconstructive approaches, from facial reanimation, laryngeal reinnervation, to variations of interposition nerve grafts for reconstruction. We discuss ongoing endeavors to promote nerve regeneration and to suppress aberrant reinnervation and the development of synkinesis. Insights from these studies will shed light on recent progress and new horizons in understanding the biomechanics of peripheral nerve neurobiology, with emphasis on promising strategies for optimizing neural regeneration and identifying future directions in the field of motor cranial neuron research.展开更多
目的:观察重组人促红细胞生成素(recombinant human erythropoietin,rhEPO)对大鼠受损面神经的保护作用及对Caspase-3表达的影响。方法:75只雌性大鼠随机分为rhEPO治疗组(n=25)、对照组(n=25)、假手术组(n=25),50只大鼠建立左侧面神经...目的:观察重组人促红细胞生成素(recombinant human erythropoietin,rhEPO)对大鼠受损面神经的保护作用及对Caspase-3表达的影响。方法:75只雌性大鼠随机分为rhEPO治疗组(n=25)、对照组(n=25)、假手术组(n=25),50只大鼠建立左侧面神经干损伤动物模型,rhEPO组大鼠致伤后即刻及每天腹腔内注射rhEPO(5000U/kg),连续两周,对照组给予等量生理盐水。分别于第3、7、14、21、28天采用Toluidine blue染色计算面神经元存活率,TUNEL检测细胞凋亡,免疫组化检测Caspase-3的表达。结果:从伤后第7天开始治疗组和对照组左侧面神经元存活率逐渐下降,每个时间点治疗组面神经元存活率明显高于对照组(P<0.05);治疗组与对照组在伤后第3天未见Tunel染色阳性细胞,对照组第7天见表达,第14天数量达高峰,治疗组在伤后第7、14、21天面神经元凋亡细胞数显著减少(P<0.05);伤后第3天对照组见Caspase-3表达增加,第14天达高峰,第28天仍见少许表达,治疗组在各时间点Caspase-3表达均明显低于对照组(P<0.05)。结论:rhEPO对受损大鼠面神经元有保护作用;降低Caspase-3的表达、抑制细胞凋亡可能是rhEPO治疗创伤性面瘫的重要机制。展开更多
文摘BACKGROUND： Erythropoietin and recombinant human erythropoietin （rhEPO） inhibit apoptosis of motor neurons caused by spinal cord injury and brain damage in rats. However, it still remains to be shown whether rhEPO can protect facial motoneurons （FMNs） as Well. OBJECTIVE： To test the neuroprotective effects of rhEPO on injured VMNs, as well as the influence on Caspase-3 expression. DESIGN, TIME AND SETTING： Randomized, controlled, animal experiment. This study was performed at the Central Laboratory of Basic Medical College, Chongqing Medical University from January to October 2007. MATERIALS： Seventy-five female SD rats, weighing 210-230 g. rhEPO injection was provided by Sansheng pharmaceuticals company, Shenyang City, Liaoning Province, China, and the License number was HMLN S20010001. METHODS： A total of 75 female rats were randomly divided into rhEPO treatment, control, and sham operation groups, with 25 rats in each group. Rat models of facial nerve injury were established in the rhEPO treatment group and the control group by crushing the main trunk of the left facial nerve. Surgical microscopic observation of the facial nerve damage displayed perineurial disruption. The left stylomastoid foramen of the sham operation group were only exposed, but without nerve injury. The rhEPO treatment group was treated with rhEPO （5 000 U/kg, i.p.） once following injury and once a day for two weeks. The control and sham operation groups were treated with the same dose of normal saline （i.p.）, once following injury and once a day for two weeks. MAIN OUTCOME MEASURES： Rats were sacrificed 3, 7, 14, 21, and 28 days after injury, FMN survival after facial nerve injury was analyzed by Toluidine blue staining, and then survival ratios （L/R） were calculated. The number of apoptotic profiles in the injured FMNs were evaluated by TUNEL staining. Expression of Caspase-3 in the facial nucleus was detected by immunohistochemistry methods. RESULTS： A total of 75 rats were included in the final analysis. FMN survival ratios, both in rhEPO treatment group and control group, decreased gradually between seven and 28 days; however, FMN survival ratios were significantly greater in the rhEPO treatment group compared to the control group （P 〈 0.05）. No TUNEL-positive cells were observed three days after injury in the rhEPO treatment and control groups; however, by seven days after injury, apoptotic cells were observed and peaked by 14 days in the control group. Between seven and 21 days, apoptotic cell numbers were significantly lower in the rhEPO treatment group compared to the control group （P 〈 0.05）. The expression of Caspase-3 increased three days after injury and peaked at 14 days in the control group. Nevertheless, Caspase-3 expression was significantly lower in the rhEPO treatment group compared to the control group at each time point （P 〈 0.05）. CONCLUSION： Treatment with rhEPO can effectively protect facial motoneurons by reducing expression of Caspase-3 and inhibiting apoptosis.
基金supported by the United States National Institute of Health grant 1K08DC012535(to MJB)Program for Neurology Research and Discoverythe Sinai Medical Staff Foundation Neuroscience Scholar Fund(to ELF)
文摘The intricate anatomy and physiology of cranial nerves have inspired clinicians and scientists to study their roles in the nervous system. Damage to motor cranial nerves may result from a variety of organic or iatrogenic insults and causes devastating functional impairment and disfigurement. Surgical innovations directed towards restoring function to injured motor cranial nerves and their associated organs have evolved to include nerve repair, grafting, substitution, and muscle transposition. In parallel with this progress, research on tissue-engineered constructs, development of bioelectrical interfaces, and modulation of the regenerative milieu through cellular, immunomodulatory, or neurotrophic mechanisms has proliferated to enhance the available repertoire of clinically applicable reconstructive options. Despite these advances, patients continue to suffer from functional limitations relating to inadequate cranial nerve regeneration, aberrant reinnervation, or incomplete recovery of neuromuscular function. These shortfalls have profound quality of life ramifications and provide an impetus to further elucidate mechanisms underlying cranial nerve denervation and to improve repair. In this review, we summarize the literature on reconstruction and regeneration of motor cranial nerves following various injury patterns. We focus on seven cranial nerves with predominantly efferent functions and highlight shared patterns of injuries and clinical manifestations. We also present an overview of the existing reconstructive approaches, from facial reanimation, laryngeal reinnervation, to variations of interposition nerve grafts for reconstruction. We discuss ongoing endeavors to promote nerve regeneration and to suppress aberrant reinnervation and the development of synkinesis. Insights from these studies will shed light on recent progress and new horizons in understanding the biomechanics of peripheral nerve neurobiology, with emphasis on promising strategies for optimizing neural regeneration and identifying future directions in the field of motor cranial neuron research.
文摘目的:观察重组人促红细胞生成素(recombinant human erythropoietin,rhEPO)对大鼠受损面神经的保护作用及对Caspase-3表达的影响。方法:75只雌性大鼠随机分为rhEPO治疗组(n=25)、对照组(n=25)、假手术组(n=25),50只大鼠建立左侧面神经干损伤动物模型,rhEPO组大鼠致伤后即刻及每天腹腔内注射rhEPO(5000U/kg),连续两周,对照组给予等量生理盐水。分别于第3、7、14、21、28天采用Toluidine blue染色计算面神经元存活率,TUNEL检测细胞凋亡,免疫组化检测Caspase-3的表达。结果:从伤后第7天开始治疗组和对照组左侧面神经元存活率逐渐下降,每个时间点治疗组面神经元存活率明显高于对照组(P<0.05);治疗组与对照组在伤后第3天未见Tunel染色阳性细胞,对照组第7天见表达,第14天数量达高峰,治疗组在伤后第7、14、21天面神经元凋亡细胞数显著减少(P<0.05);伤后第3天对照组见Caspase-3表达增加,第14天达高峰,第28天仍见少许表达,治疗组在各时间点Caspase-3表达均明显低于对照组(P<0.05)。结论:rhEPO对受损大鼠面神经元有保护作用;降低Caspase-3的表达、抑制细胞凋亡可能是rhEPO治疗创伤性面瘫的重要机制。
