促红细胞生成素与大鼠面神经损伤后运动神经元TNF-a及Bax的表达

This study sought to evaluate the effect of high-dose erythropoietin (EPO; 5 000 IU/kg) on the expression of tumor necrosis factor-alpha (TNF-α) and Bax in the facial nucleus after facial nerve transection in rats. A total of 42 Wistar rats of both genders were used in this study, and 40 rats were randomly divided into 2 groups: EPO group and model group. The EPO group was treated with EPO once a day for 5 days at a dose of 5 000 IU/kg body weight. The model group was treated with saline of the same amount. At day 3 after EPO (or saline) treatment, the right facial nerves of the 40 rats were transected at the level of the stylomastoid foramen, with the left sides untreated. The remaining 2 rats that did not undergo axotomy served as the control group. The surviving motor neurons in operated rats were counted in coronal paraffin sections of the facial nucleus. The expression of TNF-α and Bax in the facial nucleus was detected by immunohistochemical staining at days 3, 7, 14, 21, and 28 after axotomy. At days 14, 21, and 28 after facial nerve axotomy, a significantly greater proportion of facial motor neurons survived in the EPO group than in the model group. After axotomy, the expression of TNF-α and Bax increased in motor neurons in both the EPO and the model groups. TNF-α expression reached its peak level at day 14 after axotomy, while Bax expression reached its peak level at day 21. TNF-α expression was much lower in the EPO group than in the model group at all time points. No significant difference in Bax expression was found between the EPO and the model groups. These results indicate that high-dose EPO treatment attenuates the increase in TNF-α expression in the facial nucleus and reduces the loss of motor neurons after facial nerve transection in rats. However, high-dose EPO treatment has little effect on Bax expression.     

人参皂甙Rg1对去卵巢大鼠面神经核脑源性神经营养因子表达的影响：半定量分析

BACKGROUND： Estrogen is neuroprotective effects such as breast carcinoma, endometria but long-term estrogen treatment can induce side cancer, and stroke. However, phytoestrogen is neuroprotective without these side effects. OBJECTIVE： To study the effects of Ginsenoside Rgl on facial neurons and brain-derived neurotrophic factor （BDNF） expression in the facial nucleus in ovariectomized rats. DESIGN, TIME AND SETTING： The randomized, controlled animal experiments were performed at the Ultrasonic Institute, Second Affiliated Hospital, Chongqing Medical University, China, from September 2007 to September 2008. MATERIALS： Ginsenoside Rgl （Sigma, USA）, rabbit anti-rat BDNF, Bcl-2, Bax antibodies, biotin-labeled goat anti-rabbit IgG （Boster, China）, and a TUNEL kit （Roche, Germany） were used in this study. METHODS： A total of 48 adult Sprague Dawley rats undergoing ovariectomy were randomly assigned into sham operation （n = 8）, model （n = 20）, and Ginsenoside Rgl （n = 20） groups. Facial nerve damage was induced by bilateral clamping of the facial nerve trunk. The bilateral facial nerve trunk was exposed in the sham operation group, with no clamping. Rats in the Ginsenoside Rgl group were intraperitoneally injected with 10 mg/kg per day Ginsenoside Rgl; other groups received 2 mL saline, once a day, for 14 days. MAIN OUTCOME MEASURES： Morphologic changes in neurons of the facial nucleus were observed following hematoxylin-eosin staining. Neuronal apoptosis was detected by TUNEL. Changes in ultrastructure of the facial nerve fibers were observed with a transmission electron microscope. Expression of BDNF, Bcl-2, and Bax protein was quantified by semiquantitative immunohistochemistry. RESULTS： At 3-14 days following facial nerve damage, Ginsenoside Rgl increased BDNF expression and the number of regenerated nerve fibers, and produced thicker myelin sheaths （P 〈 0.05）. Ginsenoside Rgl also gradually increased Bcl-2 protein expression and decreased Bax protein expression （P 〈 0.05）. By day 7, apoptosis was observed in facial neurons, but Ginsenoside Rgl reduced the number of apoptotic neurons. Sham animals did not show any changes in BDNF, Bcl-2, or Bax expression or facial neuron morphology. CONCLUSION： Ginsenoside Rgl can substantially inhibit facial neuronal apoptosis by increasing endogenous BDNF and Bcl-2 expression and by decreasing Bax expression in ovariectomized rats after facial nerve damage.     

Acute pathological changes of facial nucleus and expressions of postsynaptic density protein-95 following facial nerve injury of varying severity★ A semi-quantitative analysis

BACKGROUND： Previous studies have demonstrated that postsynaptic density protein-95 （PSD-95） is widely distributed in the central nervous system and is related to the development of the CNS and sensory signal transmission as well as acute or chronic nerve cell death following ischemic brain injury. OBJECTIVE： To semi-quantitatively determine the pathological changes of apoptotic facial neurons and the expression of PSD-95 in the facial nucleus following facial nerve injury of varying extents using immunohistochemical staining methods. DESIGN, TIME AND SETTING： Randomized, controlled animal experiments were performed in the Ultrasonic Institute of the Second Affiliated Hospital of Chongqing University of Medical Sciences from September to December 2007. MATERIALS： Sixty-five healthy, adult, Sprague-Dawley （SD） rats, both male and female, were used for this study. Rabbit anti-rat PSD-95 polyclonal antibody was purchased from Beijing Biosynthesis Biotechnology Co., Ltd. METHODS： SD rats were randomly assigned into a control group with five rats and three injured groups with 20 rats per group. Exposure, clamp and cut for bilateral facial nerve trunks were performed in the rats of the injury groups, and no injury was inflicted on the rats of the control group. MAIN OUTCOME MEASURES; The brainstems of all the rats were excised on days 1, 3, 7, and 14 post injury, and then the facial nuclei were stained with hematoxylin-eosin to observe any pathological changes due to apoptosis in facial neurons. PSD-95 expression in facial nuclei was detected by immunohistochemistry and the number of PSD-95 positive cells was counted under a light microscope. RESULTS： The expression of PSD-95 in the facial nucleus and morphology of the facial neuron within the exposure group had no obvious changes at various points in time tested （P 〉 0.05）. However, the expressions of PSD-95 in the facial nucleus of the clamp group and cut group increased on day 1 post injury （P 〈 0.05）, and showed further increase on d     

Effects of p75 neurotrophin receptor knockout on axonal regeneration in a mouse model of facial nerve injury

BACKGROUND： Previous studies have shown that p75 neurotrophin receptor plays an important role in peripheral nerve injury. However, the role of p75 neurotrophin receptor in the regeneration of peripheral nerves remains poorly understood. OBJECTIVE： To study the effect of p75 neurotrophin receptor on facial nerve regeneration. DESIGN, TIME AND SETTING： A randomized controlled experiment was performed in the Regeneration Laboratory of Flinders University, Australia and the Biomedical Laboratory of Dentistry School, Shandong University from March 2005 to February 2006. MATERIALS： Cholera toxin B subunit, fast blue, and biotin rabbit-anti goat IgG were provided by Sigma, USA; goat-anti choleratoxin B subunit ant/body was provided by List Biologicals, USA. METHODS： In p75 neurotrophin receptor knockout and wild type 129/sv mice, the facial nerves on one side were crushed. At days 2 and 4 following injury, regenerating motor neurons in the facial nuclei were labeled by fast blue, and the regenerating axon was labeled by the anterograde tracer choleratoxin B subunit. MAIN OUTCOME MEASURES： Axonal regenerative velocity and number were detected by immunohistochemical staining of choleratoxin B subunit, growth-associated protein, protein gene product 9.5, and calcitonin-gene-related peptide; survival of motor neurons in the facial nuclei was detected by retrograde fast blue. RESULTS： Axonal growth in the facial nerve of p75 neurotrophin receptor knockout mice was significantly less than in wild type mice. At day 7 after injury, the number of regenerating motor neurons in p75 neurotrophin receptor knockout mice remained significantly less than in wild type mice （P 〈 0.05）. The number of positively stained fibers for growth-associated protein-43, protein gene product 9.5, and calcitonin-gene-related peptide in p75 neurotrophin receptor knockout mice was significantly less than in wild type mice （P 〈 0.01）. CONCLUSION： p75 neurotrophin receptor promoted axonal regeneration and enhanced the survival rate of motor neurons following facial nerve injury.     

Neuroprotective effects of recombinant human erythropoietin on facial motoneurons after facial nerve injury in rats★

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 analysi     

Amniotic membrane covering for facial nerve repair

Amniotic membranes have been widely used in ophthalmology and skin injury repair because of their anti-inflammatory properties. In this study, we measured therapeutic efficacy and determined if amniotic membranes could be used for facial nerve repair. The facial nerves of eight rats were dissected and end-to-end anastomosis was performed. Amniotic membranes were covered on the anastomosis sites in four rats. Electromyography results showed that, at the end of the 3 rd and 8 th weeks after amniotic membrane covering, the latency values of the facial nerves covered by amniotic membranes were significantly shortened and the amplitude values were significantly increased. Compared with simple facial nerve anastomosis, after histopathological examination, facial nerve anastomosed with amniotic membrane showed better continuity, milder inflammatory reactions, and more satisfactory nerve conduction. These findings suggest that amniotic membrane covering has great potential in facial nerve repair.     

听神经瘤术中面神经电生理监测的问题与对策

Objective To explore the solutions to some problems of intraoperative facial nerve monitoring during operation for acoustic neuroma and evaluate the function of anatomically preserved facial nerve. Methods The tumors were resected with suboccipital retrosigmoid approaches under microscope in 25 cases. Intraoperative monitoring was used to protect facial nerve and evaluated its function. Results Total removal was achieved in 25 patients( 100% ). The facial nerve was preserved anatomically in 23 cases(92% ),H - B Grade Ⅰ～Ⅱ in 19 cases, Grade Ⅲ～Ⅳ in 5, Grade Ⅴ～Ⅵ in 1. Stimulative intensity at the end of tumor resection was related to the function of facial nerve, and the lower was the better. The function of facial nerve might be Ⅰ～Ⅱ grade when stimulative intensity was lower than 0. 5 mA, and facial electromyograph response amplitudes was greater than 100 μV. The function of facial nerve was not ideal when stimilative intensity was above 2 mA and response amplitude was not clear. Conclusions Skilled technique of intraoperative facial nerve electrophysiologic monitoring can obviously increase the rate of anatomical and functional preservation of facial nerve, and quantitative analysis of electromyogram may help to evaluate its postoperative function.     

听神经瘤术中面神经电生理监测的问题与对策

Objective To explore the solutions to some problems of intraoperative facial nerve monitoring during operation for acoustic neuroma and evaluate the function of anatomically preserved facial nerve. Methods The tumors were resected with suboccipital retrosigmoid approaches under microscope in 25 cases. Intraoperative monitoring was used to protect facial nerve and evaluated its function. Results Total removal was achieved in 25 patients( 100% ). The facial nerve was preserved anatomically in 23 cases(92% ),H - B Grade Ⅰ～Ⅱ in 19 cases, Grade Ⅲ～Ⅳ in 5, Grade Ⅴ～Ⅵ in 1. Stimulative intensity at the end of tumor resection was related to the function of facial nerve, and the lower was the better. The function of facial nerve might be Ⅰ～Ⅱ grade when stimulative intensity was lower than 0. 5 mA, and facial electromyograph response amplitudes was greater than 100 μV. The function of facial nerve was not ideal when stimilative intensity was above 2 mA and response amplitude was not clear. Conclusions Skilled technique of intraoperative facial nerve electrophysiologic monitoring can obviously increase the rate of anatomical and functional preservation of facial nerve, and quantitative analysis of electromyogram may help to evaluate its postoperative function.     

听神经瘤术中面神经电生理监测的问题与对策

Objective To explore the solutions to some problems of intraoperative facial nerve monitoring during operation for acoustic neuroma and evaluate the function of anatomically preserved facial nerve. Methods The tumors were resected with suboccipital retrosigmoid approaches under microscope in 25 cases. Intraoperative monitoring was used to protect facial nerve and evaluated its function. Results Total removal was achieved in 25 patients( 100% ). The facial nerve was preserved anatomically in 23 cases(92% ),H - B Grade Ⅰ～Ⅱ in 19 cases, Grade Ⅲ～Ⅳ in 5, Grade Ⅴ～Ⅵ in 1. Stimulative intensity at the end of tumor resection was related to the function of facial nerve, and the lower was the better. The function of facial nerve might be Ⅰ～Ⅱ grade when stimulative intensity was lower than 0. 5 mA, and facial electromyograph response amplitudes was greater than 100 μV. The function of facial nerve was not ideal when stimilative intensity was above 2 mA and response amplitude was not clear. Conclusions Skilled technique of intraoperative facial nerve electrophysiologic monitoring can obviously increase the rate of anatomical and functional preservation of facial nerve, and quantitative analysis of electromyogram may help to evaluate its postoperative function.     

听神经瘤术中面神经电生理监测的问题与对策

Objective To explore the solutions to some problems of intraoperative facial nerve monitoring during operation for acoustic neuroma and evaluate the function of anatomically preserved facial nerve. Methods The tumors were resected with suboccipital retrosigmoid approaches under microscope in 25 cases. Intraoperative monitoring was used to protect facial nerve and evaluated its function. Results Total removal was achieved in 25 patients( 100% ). The facial nerve was preserved anatomically in 23 cases(92% ),H - B Grade Ⅰ～Ⅱ in 19 cases, Grade Ⅲ～Ⅳ in 5, Grade Ⅴ～Ⅵ in 1. Stimulative intensity at the end of tumor resection was related to the function of facial nerve, and the lower was the better. The function of facial nerve might be Ⅰ～Ⅱ grade when stimulative intensity was lower than 0. 5 mA, and facial electromyograph response amplitudes was greater than 100 μV. The function of facial nerve was not ideal when stimilative intensity was above 2 mA and response amplitude was not clear. Conclusions Skilled technique of intraoperative facial nerve electrophysiologic monitoring can obviously increase the rate of anatomical and functional preservation of facial nerve, and quantitative analysis of electromyogram may help to evaluate its postoperative function.     

Selective reinnervation of somatotopically appropriate muscles after facial nerve transection and regeneration in the neonatal rat

The organization of the facial motor nucleus (FMN) has been examined after transection and regeneration of the facial nerve (FN) in neonatal and adult rats. In one series of experiments, horseradish peroxidase (HRP) was applied bilaterally to the superior or inferior buccal ramus 5 months after neonatal FN transection. In another series of experiments, wheat germ agglutinin-horseradish peroxidase conjugate was injected in selected vibrissae follicular muscles on both sides in animals surviving 5 months after FN transection at the neonatal or adult stage. The number and distribution of HRP-labeled cell bodies in the FMN after regeneration was compared with the contralateral side. On the uninjured side, labeled neurons were somatotopically organized. Ipsilateral to nerve injury the number of labeled cells was markedly reduced after neonatal nerve transection, but somatotopy was preserved. However, after nerve lesion at the adult stage, no significant loss of motoneurons occurred, but motor nucleus somatotopy was not maintained. Two alternative principal explanations are proposed for the re-establishment of the normal somatotopy after neonatal injury: that regenerating axons grow in a random fashion but inappropriate connections are subsequently eliminated or that regenerating axons of surviving neurons immediately follow a pathway leading to the appropriate muscle.     

Prosaposin is immunolocalized to muscle and prosaptides promote myoblast fusion and attenuate loss of muscle mass after nerve injury

Prosaposin is the precursor of the saposins and has both neurotrophic and myelinotrophic activity in vitro and in vivo. Using an antibody specific for the holoprotein, an immunocytochemical survey demonstrated intense staining of adult rat skeletal, cardiac, and smooth muscle cells. Prosaposin immunoreactivity in muscle appears dependent on innervation, as denervated adult rat skeletal muscles showed decreased immunostaining that returned to normal levels after reinnervation. TX14(A), a peptide derived from the neurotrophic sequence of prosaposin, attenuated the decline in muscle mass loss following nerve injury induced by a constricting ligature. In vitro, both L6 myoblasts and primary chick-embryo myoblasts showed similar prosaposin immunopositivity, mainly in myotubes. TX14(A) induced a threefold increase in L6 myoblast fusion during early stages of differentiation without affecting cell proliferation. The fusion process was decreased in vitro in a dose-dependent fashion by addition of a neutralizing anti-prosaposin antibody. These data suggest that, in addition to neurotrophic and myelinotrophic activities, prosaposin has myotrophic properties.     

Changes in growth inhibitory factor mRNA expression compared with those in c-jun mRNA expression following facial nerve transection

We investigated growth inhibitory factor (GIF) mRNA expression within the rat facial nucleus with the aid of in situ hybridization. We found that GIF mRNA was expressed abundantly in the facial motoneurons of sham operated animals, and that this gene expression decreased after transection of the facial nerve. This decrease of GIF mRNA was first detected on the third day and was maintained for at least five weeks after transection of the nerve. Changes in c-jun, an immediate early gene, were also investigated with this model, and it was found that c-jun mRNA started to increase in the facial nucleus on the first day and that this increase was maintained for at least 5 weeks. These results suggest that the facial motoneurons, when their axons are transected, continuously respond to the injury and that GIF mRNA is actively suppressed to reduce the inhibition of neurite outgrowth in order to regenerate the axons.     

Differential expression of Fos protein after transection of the rat infraorbital nerve in the trigeminal nucleus caudalis

To determine the effects of nerve injury on Fos expression, temporal and spatial distributions of Fos-positive neurons in the trigeminal nucleus caudalis were examined after tissue injury for isolation of the infraorbital nerve as controls and transection of this nerve as well as noxious chemical stimulation by formalin injection in adult rats. Fos immunoreactivity was markedly elevated in laminae I and II of the only ipsilateral nucleus caudalis 2 h after these surgical procedures and noxious chemical stimulation. The distributions of Fos-positive neurons were restricted rostro-caudally following formalin injection and tissue injury compared to transection of the infraorbital nerve. One day after tissue injury and nerve transection, however, Fos-positive neurons were distributed bilaterally in laminae III and IV extending rostro-caudally and medio-laterally in this nucleus, and this persisted over the 2-week study period. The number of Fos-positive neurons in the side ipsilateral to nerve transection was markedly less than that in the contralateral side whereas positive neurons in the tissue injured rats were distributed symmetrically along the rostro-caudal axis. There was no difference in the contralateral sides between nerve transection and tissue injury groups. The rostro-caudal level showing reduction in Fos expression corresponded roughly to the sites of central termination of the injured nerve in this nucleus, suggesting a role for the primary afferents in the reduction of Fos expression in laminae III and IV neurons of the ipsilateral nucleus caudalis.     

面神经保留程度对神经再生及重建眼轮匝肌功能影响的实验研究

目的探讨保留不同程度的再生面神经对面神经-舌下神经侧-侧吻合术后大鼠眼轮匝肌功能重建的作用。方法采用随机抽样分组的方法,将40只大鼠分为4组(每组10只),4组大鼠均行面神经钳夹线拴损伤及面神经-舌下神经侧-侧吻合术(简称吻合术)。术后3个月,A组(对照组):模型建立后不做任何处理;B组:横截断结扎线近头端面神经1/3部分;C组:横截断结扎线近头端面神经2/3部分;D组:于面神经结扎线近头端全部离断面神经。分别于吻合术后1、2、3个月和横截断面神经1周后采用瞬目反应评分评估大鼠患侧眼睑的闭合程度;行运动诱发电位(MAPs)检测大鼠患侧眼轮匝肌的动作电位幅度及波幅下面积;神经元逆行示踪检测面神经核及舌下神经核内阳性神经元的数量;面神经及移植神经半薄切片计数髓鞘数目。结果4组大鼠吻合术后1、2、3个月的瞬目反应评分比较差异均有统计学意义(F值分别为12.47、11.00、10.61、19.13,均P<0.05);横截断面神经1周后4组瞬目反应评分的差异有统计学意义(F=29.06,P<0.05),其中D组分别低于A组和B组(均P<0.01);横截断面神经1周后,刺激面神经吻合口近头端及移植神经中点,4组的MAPs波幅及波幅下面积的差异均有统计学意义(F值分别为27.56、11.86、6.33、4.65,均P<0.05),其中D组的MAPs波幅及波幅下面积均低于A组(均P<0.05)。神经元逆行示踪显示,4组的面神经核内阳性神经元计数的差异有统计学意义(F=6.52,P<0.05),其中D组的阳性神经元数量分别低于A组和B组(均P<0.05)。4组的面神经干及移植神经中段髓鞘计数差异均有统计学意义(F值分别为8.33、6.35,均P<0.05),其中A组分别高于C组和D组(均P<0.05)。结论面-舌吻合术中保留面神经结构完整性具有积极意义,至少保留2/3再生面神经对眼轮匝肌恢复有利。     

睫状神经营养因子对面神经损伤修复大鼠面神经核内STAT3磷酸化的影响

目的 探讨重组人睫状神经营养因子（ciliary neurotrophica factor．CNTF）对面神经损伤修复大鼠面神经核运动神经元STAT3活性的影响。方法 成年大鼠面神经切断后行端端吻合．局部给予CNTF．以生理盐水为对照。术后7d．运用抗磷酸化STAT3抗体做免疫印迹（immuobloting，IB）以检测面神经核抽提物STAT3的磷酸化变化。结果 局部给予CNTF组大鼠面神经核内p-STAT含量较对照组高（P〈0．05）。结论 局部给予重组CNTF可增强面神经损伤修复大鼠面神经核内STAT3的磷酸化。     

BDNF atelocollagen mini-pellet accelerates facial nerve regeneration

We investigated the effect of BDNF mini-pellet on the GAP-43 mRNA expression and functional status of facial nerve in a rat model of facial nerve transection and immediate repair. The facial function started to recover at 17 days in the placebo group and 14 days in the BDNF group. BDNF group had shorter period of increased GAP-43 mRNA expression than the placebo group. Topically applied BDNF may accelerate the facial nerve regeneration.     

Basic FGF in adult rat brain: cellular distribution and response to entorhinal lesion and fimbria-fornix transection.

Basic fibroblast growth factor (bFGF) is a potent trophic factor for neurons and astrocytes and recently has been implicated in the pathology of Alzheimer's disease. In order to better understand the role of bFGF in normal brain function and during pathology, we have analyzed its anatomical distribution and its response to injury in the CNS. Double-staining immunohistochemistry showed that bFGF immunoreactivity was localized in astrocytes, in select neuronal populations, and occasionally in microglial cells throughout the normal rat brain. Neuronal populations that showed bFGF immunoreactivity included septohippocampal nucleus, cingulate cortex, subfield CA2 of the hippocampus, cerebellar Purkinje cells, cerebellar deep nuclei, facial nerve nucleus, and the motor and spinal subdivisions of the trigeminal nucleus and facial nerve nucleus. The pattern of bFGF immunoreactivity in the hippocampus was examined following entorhinal cortex lesion, or fimbria-fornix transection. After entorhinal cortex lesion, bFGF immunoreactivity increased in the outer molecular layer of the dentate gyrus ipsilateral to the lesion. The lesion effect on bFGF immunoreactivity was expressed as an increase in the number of bFGF astrocytes, as an increase in the intensity of bFGF immunoreactivity within astrocytes, and as an increase of bFGF immunoreactivity in the surrounding extracellular matrix, relative to the contralateral side. The time course and pattern of reorganization paralleled the sprouting of septal cholinergic terminals in response to the same type of lesion, suggesting that bFGF may play an important role in lesion-induced plasticity. After transection of the fimbria-fornix, chronic infusion of bFGF appeared to preserve NGF receptors on neurons within the medial septal complex and, as previously reported, prevent the death of medial septal neurons. Therefore, it appears that bFGF infusion, which has been shown to increase the synthesis of NGF by astrocytes (Yoshida and Gage, 1991), also helps enable neurons to respond to NGF. This suggests that after injury bFGF may participate in a cascade of neurotrophic events, directly and indirectly facilitating neuronal repair and/or promoting neuronal survival.     

Axotomy of rat facial nerve induces TGF-β and latent TGF-β binding protein

Transforming growth factor-β (TGF-β) has been found to be abundantly and specifically expressed in the nervous system. However, the function of TGF-β during nerve regeneration is still unknown. We have examined the expression of TGF-β isoforms and the latent TGF-β binding protein (LTBP) by immunofnistochemistry in the rat facial nuclei after unilateral axotomy. An increased immunoreactivity for all the TGF-β isoforms and the LTBP was observed in the facial nuclei of the injured side during the regeneration period examined until Day 24. These differences were tested statistically by nominal logistic regression analysis. When the intensity of the immunoreactivity in the injured side was compared to that of the contralateral side, significantly increasing differences were found for TGF-β2 (p < 0.003) and LTBP (p < 0.002). Strong immunostaining was detected in the neuronal perikarya and their axons. No clear immunoreactivity, was seen in either microglia or astrocytes. The enhanced immunoreactivity was seen in the operated side already at Day 3, remaining at high level with some fluctuations until Day 12 or 24 after axotomy. These findings suggest that TGF-β might play a functional role in the regeneration of motor neurons.