Glial cell line-derived neurotrophic factor (GDNF) is expressed in the human kidney and is a growth factor for human mesangial cells.

BACKGROUND: Glial cell line-derived neurotrophic factor (GDNF), a recently cloned member of the transforming growth factor-beta (TGF-beta) superfamily, is a potent neurotrophic factor in vitro and in vivo. GDNF is essential for nephrogenesis and the highest expression of GDNF is found in the developing kidney. Increased plasma GDNF levels have recently been documented in patients with chronic renal failure; the source and role of this increase, however, remain unclear. No data are available about the expression of GDNF in human adult kidney or human adult mesangial cell (HMC) cultures. We hypothesized that GDNF, similar to other members of the TGF-beta superfamily, might play a role as a growth factor in the pathogenesis of glomerulosclerosis. METHODS: To address this hypothesis, we first investigated (by RT-PCR) the expression of GDNF mRNA and the mRNAs of the GDNF receptors Ret and GFRalpha-1 in (i) adult human renal cortex and medulla and (ii) in HMC in culture. The results were compared to the expression of these molecules in different developmental stages of the rat kidney. We found that both GDNF and its receptors were expressed in human adult kidney and HMC. Since this finding implicates a role for GDNF beyond nephrogenesis, i.e. in renal physiology/pathophysiology, we investigated the effect of GDNF on HMC growth, i.e. (i) cellular protein synthesis as an index of hypertrophy ([(3)H]methionine incorporation), (ii) DNA synthesis ([(3)H]thymidine incorporation) and cell proliferation (cell numbers) as indices of hyperplasia, and (iii) extracellular matrix synthesis, i.e. collagenous and non-collagenous extracellular proteins ([(3)H]proline incorporation into the collagenase-sensitive and -insensitive fraction). HMC cultures were used as a surrogate model for the development of glomerulosclerosis. RESULTS: GDNF induced a biphasic growth stimulatory effect in HMC with stimulation at the lowest concentration used (2 ng/ml) but had no effect at higher concentrations (20 and 50 ng/ml). In contrast, cellular protein synthesis and extracellular matrix synthesis were significantly and dose-dependently increased by GDNF. CONCLUSIONS: These results suggest that GDNF, similar to other members of the TGF-beta superfamily, might play a role as a growth factor for mesangial cells and might thus be a player in the pathogenesis of glomerulosclerosis.     

胶质细胞源性神经营养因子对体外培养小鼠精原干细胞增殖分化作用的影响

目的 探讨胶质细胞源性神经营养因子(GDNF)对体外培养小鼠精原干细胞(SSC)增殖与分化的影响.方法 雄性昆明小鼠80只.采用Percoll密度梯度分离及差速贴壁法纯化SSC,免疫荧光染色及流式细胞检测方法鉴定.将获取的SSC随机分为实验组和对照组,以支持细胞作为饲养层培养SSC,实验组每5 ml DMEM/F12完全培养液中添加0.02 μg GDNF.酶联仪检测细胞生长情况,流式细胞仪检测细胞生长周期;采用卵泡浆内显微注射(ICSI)技术将精子细胞与卵母细胞结合,观察卵裂细胞数,体外培养3 d后行染色体数量分析.结果 添加GDNF培养的SSC第6、9、12、15天吸光度(A)值分别为0.448±0.028、0.502±0.062、0.556±0.045、0.621±0.072,与对照组0.377±0.053、0.402±0.071、0.432±0.019、0.461±0.037比较差异有统计学意义(P＜0.05);第3、6、9、12、15天SSC DNA合成期(S期)含量分别为20.86、26.34、31.23、37.54、28.02,与对照组1.69、1.73、2.56,4.85,1.82比较差异均有统计学意义(P＜0.05);精子细胞与卵母细胞结合后可得到含有20对染色体的配子.结论 ICSI技术可为鉴定SSC体外分化为精子细胞提供较充分的依据;GDNF能促进SSC的体外增殖与分化.     

人GDNF基因的腺病毒载体构建及其在人神经干细胞中的表达

目的：观察构建的含人胶质细胞源性生长因子（GDNF）基因腺病毒载体对人神经干细胞的感染及其基因表达情况,为脊髓损伤的基因及神经干细胞治疗提供前期实验依据。方法：从12周龄流产人新鲜胚胎中提取人神经干细胞并进行培养,行Nestin免疫荧光染色进行检验。将全长558bp编码人GDNF的cDNA克隆到重组腺病毒载体质粒,并在人胚肾细胞（HEK293细胞）中包装出含有目的基因hGDNF的腺病毒,然后用该腺病毒感染人神经干细胞,应用荧光显微镜和Western-blot检测病毒感染及外源基因的表达情况,并进行GFAP和Tubulin免疫荧光染色检测神经干细胞向神经细胞分化情况。结果：Nestin免疫荧光染色显示所培养细胞为阳性染色红色,表明其具有神经干细胞性状;感染48h后观察到神经干细胞中有大量的增强绿色荧光蛋白（EGFP）表达,以及hGDNF蛋白高表达;感染后的神经干细胞有长的伪足伸出,呈GFAP和Tubulin染色阳性,表明促进了神经干细胞向神经元的分化。结论：腺病毒对神经干细胞具有较高感染效率,可作为一种良好的基因导入载体,实现外源基因hGDNF在神经干细胞内的有效表达,并可为神经干细胞分化为神经元提供更有利条件。     

Convective delivery of glial cell line-derived neurotrophic factor in the human putamen

OBJECT: The authors conducted an analysis of the distribution of glial cell line-derived neurotrophic factor in the human striatum following convection-enhanced delivery. METHODS: Computational examinations of the effects of differing catheters, infusion rates, infusate concentrations, and target placement on distribution were completed based on the protocols of three recent clinical trials. RESULTS: Similar drug distributions around on-target end-hole catheters were predicted in two of the trials (AmgenUT study and Bristol study), although there was slightly deeper penetration for one of the trials (Bristol) due to a higher infusate concentration. However, when positioning uncertainly located catheter tips close to gray-white matter interfaces, backflow could diminish delivery, shunting infusate across the interfaces. For delivery via a multiport catheter at a constant base infusion rate plus a periodic bolus inflow rate (Kentucky study), base inflow alone generated a somewhat smaller distribution volume relative to those in the other trials, was positioned more anteriorly in the putamen, and was somewhat elongated axially; the bolus component extended this putaminal distribution to a larger relative volume but may have been reduced by backflow loss. CONCLUSIONS: Results of these computations indicated that for catheters placed exactly on the intended target, ideal drug distributions were similar for two of the trials (AmgenUT and Bristol) and different in terms of location and extent in the third study (Kentucky); yet the pattern of trial outcomes did not reflect these same groupings. This finding suggests that other factors are at play, widely varying statistical power and the possible effects of not excluding data from patients who experienced large drug losses across gray tissue boundaries due to variation in catheter placement.     

Glial cell line-derived neurotrophic factor and its receptor ret is a novel ligand-receptor complex critical for survival response during podocyte injury

Glomerulosclerosis correlates with a reduction in podocyte number that occurs through mechanisms that include apoptosis. Whether glial cell line-derived neurotrophic factor (GDNF), a growth factor that is critical for neural and renal development, is a survival factor for injured podocytes was investigated. Ret, the GDNF receptor tyrosine kinase, was upregulated in podocytes in the passive Heymann nephritis and puromycin aminonucleoside (PA) nephrosis rat models of podocyte injury. In addition, Ret mRNA and protein were upregulated in mouse podocytes in vitro after injury that was induced by sublytic C5b-9 and PA. GDNF, which also was induced during podocyte injury, inhibited significantly the apoptosis of podocytes that was induced by ultraviolet C irradiation. Knockdown of Ret expression by small interference RNA in podocytes exacerbated apoptosis that was induced by both ultraviolet C and PA. Ret knockdown, upon injury, decreased AKT phosphorylation, suggesting that the phosphoinositol-3 kinase/AKT pathway mediated the survival effect of GDNF on podocytes. Consistent with this hypothesis, the selective phosphoinositol-3 kinase inhibitor LY294002 blocked the survival-promoting effects of GDNF. In conclusion, GDNF is a novel podocyte survival factor. Furthermore, Ret is highly upregulated during podocyte injury in vitro and in vivo, suggesting that Ret activation is a critical adaptive response for podocyte remodeling and repair.     

Sciatic nerve regeneration by microporous nerve conduits seeded with glial cell line-derived neurotrophic factor or brain-derived neurotrophic factor gene transfected neural stem cells

Neurotrophic factors such as the glial cell line-derived neurotrophic factor (GDNF) and brain-derived neurotrophic factor (BDNF) promote nerve cell survival and regeneration, but their efficacy in repairing a longer gap defect of rat sciatic nerve (15 mm) has not been established. In this study, two recombinant mammalian vectors containing either rat GDNF gene or BDNF gene were constructed and each was transfected into neural stem cells (NSCs). It was found that the transfection of GDNF or BDNF gene into NSCs led to significantly enhanced expression of GDNF or BDNF mRNA. The amount of GDNF or BDNF protein secreted from the transfected NSCs showed a 3.3-fold or 2.5-fold increase than that from nontransfected NSCs, respectively. The regeneration capacity of rat sciatic nerve in a poly(D,L-lactide) conduit seeded with GDNF or BDNF-transfected NSCs was evaluated by the histology, functional gait, and electrophysiology after 8 weeks of implantation. It was observed that the degree of myelination and the size of regenerated tissue in the conduits seeded with GDNF- and BDNF-transfected NSCs were higher than those seeded with the nontransfected NSCs. Conduits seeded with GDNF-transfected NSCs had the greatest number of blood vessels. The functional recovery assessed by the functional gait and electrophysiology was significantly improved for conduits seeded with GDNF or BDNF-transfected NSCs. It was concluded that the genetically modified NSCs may have potential applications in promoting nerve regeneration and functional recovery.     

胶质细胞源性神经营养因子慢病毒载体体外转染嗅鞘细胞MOI值的研究

目的 探讨胶质细胞源性神经营养因子(GDNF)慢病毒载体(lentivirus vector)体外转染嗅鞘细胞(OECs)并能稳定表达目的 蛋白的最佳感染复数(MOI).方法 构建GDNF-lentivirus,体外转染293T细胞,获得高滴度的慢病毒浓缩液,测定病毒滴度达2×108 TU/ml.不同MOI的情况下,GDNF-lentivirus体外转染OECs,Western blot检测GDNF的表达.结果 相差显微镜明视野下动态观察转染后的OECs生长状态良好,荧光显微镜下见大量绿色荧光蛋白(GFP)标记的转染成功的OECs.MOI=100时,OECs的转染率最高,约为75%,MOI=50时约为68%,MOI=10和MOI=1时分别为25%和13%,阴性对照组未见有绿色荧光表达.转染后第5天,收集OECs进行Western blot检测,MOI=100和MOI=50时GDNF表达最强,两者差异无统计学意义(P＞0.05),MOI=10表达较少,而MOI=1表达最少,对照组无GDNF表达.结论 GDNF-lentivirus在体外既能高效转染OECs又不影响细胞活性,且转染后的OECs可以长期稳定表达GDNF的适宜MOI为50～100之间.     

蛛网膜下腔灌注胶质细胞源性神经营养因子对损伤脊髓再生及功能恢复的影响

目的：探讨胶质细胞源性神经营养因子（GDNF）对大鼠脊髓完全性横断后脊髓再生及功能恢复的影响。方法：采用大鼠胸段（T7-T8）脊髓完全横切损伤模型，将SD雌性大鼠随机分为正常组（n=6）、假手术组（n=6）、单纯横断组（n=10）、GDNF治疗组（n=10）。于大鼠脊髓损伤术后不同时间点进行行为学评估。24周时行生物素葡聚糖胺（BDA）顺行示踪处理，取材前行电生理检测。所取脊髓标本作神经中丝（NF-200）、生长相关肽-43（GAP-43）、胶质原纤维生长蛋白（GFAP）免疫组化检查，并应用图像分析系统进行定量分析。结果：行为学评分表明，3周后，GDNF组好于单纯横断组（P〈O．05），术后24周，GDNF组和单纯脊髓横断组中均未记录到SEP波形，BDA示踪也未见伤区及远段蓝染的神经纤维，但GDNF组空泡样变较单纯横断组轻。免疫组化图像分析GDNF组的NF-200和GAP-43染色结果与单纯横断组间无统计学差异（P〉0．05）：但GDNF组GFAP染色明显弱于单纯横断组（P〈0．05）。结论：GDNF能一定程度上改善脊髓损伤区及两端的神经细胞功能，但没有功能意义上的神经纤维再生。     

胶质细胞源性神经营养因子基因修饰的雪旺细胞对大鼠坐骨神经缺损的修复作用

目的　研究胶质细胞源性神经营养因子 (glialcellline derivesneurotrophicfactor ,GDNF)基因对周围神经断伤后促进轴突再生及神经元的保护作用。方法　应用体外获取的GDNF修饰的雪旺细胞结合细胞外基质凝胶及生物可降解聚乳酸 聚羟基乙酸共聚物管 (polyCDL lactide co glycolide ,PLGA)构建的神经移植复合体 ,修复大鼠坐骨神经的缺损。 2 0只成年Wistar大鼠按桥接物的不同随机分为 4组 ,每组 5只。A组 :细胞外基质凝胶 PLGA管桥接组 ;B组 :雪旺细胞 细胞外基质凝胶 PLGA管桥接组 ;C组 :GDNF基因修饰的雪旺细胞 细胞外基质凝胶 PLGA管桥接组 ;D组 :自体神经桥接组。术后 12周检测运动神经传导速度 ,并进行再生神经的组织形态学观察以及计量学分析。结果　术后 12周 ,坐骨神经的运动神经传导速度 ,轴突数、髓鞘的厚度、神经纤维的直径、神经组织面积的百分比和脊髓前角运动神经元存活率等 ,C组均优于A、B组 (P <0 .0 1) ,而与D组相比无明显差异 (P >0 .0 5 )。结论　雪旺细胞的转基因处理可能弥补单纯细胞移植神经营养因子含量的不足 ,而达到与自体神经移植相似的效果。     

Glial cell line-derived neurotrophic factor-supplemented hibernation of fetal ventral mesencephalic neurons for transplantation in Parkinson disease: long-term storage

OBJECT: Transplantation of fetal dopaminergic tissue is being investigated in animal models and clinical trials for its potential as a treatment for advanced Parkinson disease. At the same time, the availability of fetal tissue is limited, making its storage time prior to transplantation a key practical issue. Although it results in a smaller percentage of surviving cells. a longer storage time enables fetal tissue obtained over several days to be pooled for transplantation in a recipient. Glial cell line-derived neurotrophic factor (GDNF) has been shown to improve survival of human dopaminergic tissue that has been stored prior to transplantation. The objective of this study was to evaluate the effects on fetal dopaminergic tissue of GDNF-supplemented hibernation for extended periods of 6 to 15 days. METHODS: The ventral mesencephalon (VM) was harvested in a total of 27 14-day-old rat fetuses, and three VMs were cultured immediately (fresh control group). The remaining 24 VMs were divided sagittally along the midline to yield 48 equal pieces of hemimesencephalon. Twenty-four pieces were stored with GDNF-supplemented hibernation medium for 6, 9, 12, or 15 days, and the 24 "partner" hemimesencephalon pieces were stored in control hibernation medium for the same periods of time. Tissue was cultured for 48 hours and processed for tyrosine hydroxylase (TH) immunoreactivity and double-stained with cresyl violet. Cell counts for all cultures and the percentage of TH-immunoreactive cells were obtained. The percentage of TH-immunoreactive cells for the fresh control group was 6.3 +/- 0.5%. The percentage of TH-immunoreactive cells in cultures derived from tissue stored in GDNF-supplemented medium was significantly increased at 6 and 9 days posthibernation compared with the fresh control group and the "partner" groups stored in hibernation medium only. No significant increase in the percentage of TH-immunoreactive cells was observed in the 12- and 15-day groups. CONCLUSIONS: In this study the authors have demonstrated that fetal dopaminergic tissue can be safely stored for up to 9 days in GDNF-supplemented hibernation medium. Furthermore, the percentage of TH-immunoreactive cells is significantly increased after 6 and 9 days of storage in this medium, improving the yield of TH-immunoreactive cells prior to transplantation. These observations have practical clinical implications for collecting fetal dopaminergic cells and improving their survival after transplantation.     

胶质细胞源性神经营养因子对脑出血大鼠保护作用的研究

目的探讨胶质细胞源性营养因子(GDNF)对脑出血大鼠的保护作用.为临床研究提供理论依据.方法选用成年SD大鼠制备脑出血模型,克隆胚胎鼠的GDNF基因,构建pcDNA3-GDNF-GFP质粒,注射于大鼠脑出血部位,分别在不同时间点观察对出血后脑组织的影响.结果与对照组相比,GDNF能降低脑出血大鼠的神经缺损评分,降低脑组织含水量和血脑屏障通透性,减小出血后的血肿体积和最大坏死面积,且能增加脑组织GDNF阳性细胞的表达.结论GDNF能改善脑出血大鼠的行为学,减轻脑水肿,促进神经功能的恢复,增加脑组织的抗损伤能力,有一定的治疗意义.     

Association of intratubular seminoma and intratubular embryonal carcinoma with invasive testicular germ cell tumors

The classification of intratubular germ cell neoplasia of the testis includes an unclassified type (IGCNU), in addition to various other intratubular lesions that show specific forms of differentiation, such as intratubular seminoma and intratubular embryonal carcinoma. Although IGCNU is recognized as a precursor lesion for testicular germ cell tumors, the relationship between differentiated types of intratubular germ cell neoplasia and invasive germ cell tumors of the testis is not well established. The aim of the present study was to examine the association between invasive testicular germ cell tumors and intratubular neoplastic lesions, with particular emphasis on differentiated types of intratubular germ cell neoplasia. The seminiferous tubules adjacent to 42 testicular germ cell tumors were evaluated for the presence of various forms of intratubular germ cell neoplasia. IGCNU was observed in 37 (88%) of 42 cases, whereas intratubular seminoma and intratubular embryonal carcinoma were seen in 19% and 7% of the cases, respectively. Intratubular seminoma was associated primarily with seminomas or mixed germ cell tumors with a seminomatous component, but was also present in a case of a nonseminomatous germ cell tumor. Intratubular embryonal carcinoma was associated exclusively with nonseminomatous germ cell tumors. All cases of intratubular embryonal carcinoma were identified morphologically and exhibited histologic features corresponding to traditional definitions of this lesion. No examples of intratubular embryonal carcinoma as defined by CD30 expression alone in the absence of an intratubular proliferation were observed. The presence of intratubular seminoma in a nonseminomatous germ cell tumor suggests that it is a true preinvasive lesion rather than a manifestation of intratubular spread of an established invasive seminoma. The low incidence of intratubular embryonal carcinoma supports the theory that most nonseminomatous germ cell tumors evolve initially as seminomas, rather than directly from a differentiated intratubular neoplastic lesion.     

Grafting of nigral tissue hibernated with tirilazad mesylate and glial cell line-derived neurotrophic factor

Transplantation of embryonic ventral mesencephalon is a potential therapy for patients with Parkinson's disease. As only around 5-10% of embryonic dopaminergic neurons survive grafting into the adult striatum, it is considered necessary to use multiple donor embryos. To increase the survival of the grafted dopaminergic neurons, the clinical transplantation program in Lund currently employs the lipid peroxidation inhibitor, tirilazad mesylate, in all solutions used during tissue storage, preparation, and transplantation. However, the difficulty in obtaining a sufficient number of donor embryos still remains an important limiting factor for the clinical application of neural transplantation. In many clinical transplantation programs, it would be a great advantage if human nigral donor tissue could be stored for at least 1 week. This study was performed in order to investigate whether storage of embryonic tissue at 4 degrees C for 8 days can be applied clinically without creating a need to increase the number of donors. We compared the survival of freshly grafted rat nigral tissue, prepared according to the clinical protocol, with tissue transplanted after hibernation. Thus, in all groups tirilazad mesylate was omnipresent. One group of rats was implanted with fresh tissue and three groups with hibernated tissue with or without addition of glial cell line-derived neurotrophic factor (GDNF) in the hibernation medium and/or the final cell suspension. Earlier studies have suggested that GDNF improves the survival of hibernated nigral transplants. We found no statistically significant difference between the groups regarding graft survival after 3 weeks. However, there was a nonsignificant trend for fewer surviving dopaminergic neurons in grafts from hibernated tissue compared to fresh controls. Furthermore, we show that the addition of GDNF to the hibernation medium and/or to the final cell suspension does not significantly increase the survival of the dopaminergic neurons.     

Expression of glial cell line-derived neurotrophic factor family members and their receptors in pancreatic cancers

BACKGROUND: The glial cell line-derived neurotrophic factor (GDNF) is a member of neurotrophic polypeptide family, which promotes survival and rescue of various neural cells in the central and peripheral nerve systems. We previously reported that GDNF promotes tumor cell invasion in pancreatic cancer cell lines. The purpose of this study was to investigate GDNF family expression and the status of related receptors in actual cancer tissues, and assess correlations with clinicopathologic behavior. METHODS: Immunohistochemical assessment of GDNF, neurturin, persephin, artemin, GDNF family receptor alpha-1 and alpha-2, and RET was performed for 51 cases of surgically resected pancreatic cancer. RESULTS: In all intrapancreatic nerves, GDNF and artermin were expressed strongly. In pancreatic cancer tissues. The expression of RET was stronger than that seen in normal ductal cells and was significantly related to the survival rate after resection (P = .026) and lymphatic invasion (P = .014). Intrapancreatic neural invasion was significantly related to the expression of GDNF (P = .047). CONCLUSIONS: We conclude that the expression of RET in pancreatic cancer tissues may be a useful prognostic marker and GDNF may play an important role in neural invasion.     

胶质细胞源性神经营养因子对股骨头缺血坏死的保护作用

目的探究胶质细胞源性神经营养因子(glial cell line-derived neurotrophic factor,GDNF)对早期激素性股骨头坏死(steroid-induced avascular necrosis of the femoral head,SANFH)的保护作用。方法采用改良技术建立早期激素性股骨头坏死兔模型,随机分成实验组(n=12)和对照组(n=12)。实验组给予髋周臀大肌注射GDNF(8.0μg/只),对照组相同部位注射等体积生理盐水,干预1周。分别于第5、10、15、20天进行股骨头多排螺旋CT、显微CT及苏木素-伊红(HE)染色检测。结果影像学观察示,GDNF注射后第15天开始,实验组股骨头骨小梁逐渐丰富、密集,间距变窄,骨皮质厚度及密度增加;对照组股骨头骨小梁分布稀疏,间距增宽,部分断裂,骨质密度减低。第15、20天,实验组与对照组股骨头骨矿物质密度、组织骨矿物质密度及骨体积分数,比较差异具有统计学意义(P0.05)。组织学观察示,实验组股骨头内骨小梁粗大,骨细胞分布广泛,细胞核着色深,脂肪细胞分布较少;对照组骨小梁分布稀疏,形态不完整,部分断裂,骨细胞空陷窝和脂肪细胞增多,骨细胞和造血细胞减少。第15、20天,实验组与对照组股骨头骨细胞空陷窝率分别为:13.3±3.2%、10.6±2.4%和71.0±7.5%、78.6±5.3%,两组比较,实验组骨细胞空陷窝率显著减低(P0.05)。结论 GDNF可通过抑制骨细胞坏死,保持骨小梁的完整性。     

Protective effects of glial cell line-derived neurotrophic factor on hippocampal neurons after traumatic brain injury in rats

OBJECT: The purpose of this study was to evaluate whether glial cell line-derived neurotrophic factor (GDNF) can protect against hippocampal neuronal death after traumatic brain injury (TBI). METHODS: Male Sprague-Dawley rats were subjected to moderate TBI with a controlled cortical impact device while in a state of halothane-induced anesthesia. Then, GDNF or artificial cerebrospinal fluid ([aCSF]; vehicle) was infused into the frontal horn of the left lateral ventricle. In eight brain-injured and eight sham-operated rats, GDNF was infused continuously for 7 days (200 ng/day intracerebroventricularly at a rate of 8.35 ng/0.5 microl/hour). An equal volume of vehicle was infused at the same rate into the remaining eight brain-injured and eight sham-operated rats. Seven days post-injury, all rats were killed. Their brains were sectioned and stained with cresyl violet, and the hippocampal neuronal loss was evaluated in the CA2 and CA3 regions with the aid of microscopy. A parallel set of sections from each brain was subjected to immunoreaction with antibodies against glial fibrillary acidic protein (GFAP; astroglia marker). In the aCSF-treated group, TBI resulted in a significant neuronal loss in the CA2 (60%, p < 0.05) and CA3 regions (68%, p < 0.05) compared with the sham-operated control animals. Compared with control rats infused with aCSF, GDNF infusion significantly decreased the TBI-induced neuronal loss in both the CA2 (58%, p < 0.05) and CA3 regions (51%, p < 0.05). There was no difference in the number of GFAP-positive astroglial cells in the GDNF-infused rats in the TBI and sham-operated groups compared with the respective vehicle-treated groups. CONCLUSIONS: The authors found that GDNF treatment following TBI is neuroprotective.