Brain-derived neurotrophic factor reduces TrkB protein and mRNA in the normal retina and following optic nerve crush in adult rats

Brain-derived neurotrophic factor (BDNF) is a well-known retinal neuroprotectant, but its effectiveness is limited: higher doses do not yield increased cell survival, multiple applications are not additive, and long-term delivery does not reverse, ganglion cell death. These limitations might reflect either injury- or BDNF-induced retinal changes in TrkB, the high affinity tyrosine kinase receptor used by BDNF. Retinal levels of TrkB protein and mRNA were measured in rats following intravitreal application of BDNF alone, optic nerve crush alone, and both. Full-length receptor protein levels (TrkB.FL) were determined by Western blot analysis and mRNA (trkB.FL) levels were measured using RNAse protection assay (RPA). BDNF alone produced a rapid and prolonged decrease in normal retina TrkB.FL. Nerve crush also resulted in decreased TrkB.FL, but the reduction was not apparent before 2-week post-crush. BDNF applied at the time of the crush yielded reductions in TrkB.FL similar to that of BDNF alone. With respect to TrkB mRNA levels, injection of BDNF into normal eyes and optic nerve crush alone showed bell-shaped patterns of change: approximately 50% below normal at 24-h post-procedure, approximately 50% above normal at 3 days, normal at 7 days, and approximately 50% below normal at 2-week post-procedure. When BDNF and nerve crush were combined, trkB-FL levels reached 90% of normal 1-week post-crush/injection. The data suggest that the limitation of BDNF in promoting ganglion cell survival following optic nerve injury results, in part, due to drug-induced down-regulation of the full-length TrkB receptor needed to activate intracellular pathways.     

Prevention of endoplasmic reticulum stress-induced cell death by brain-derived neurotrophic factor in cultured cerebral cortical neurons

Brain-derived neurotrophic factor (BDNF), one of the neurotrophic factors acting in the central nervous system (CNS), prevents ordinary types of neuronal cell death induced by various stimulants. On the other hand, an accumulation of unfolded proteins in the endoplasmic reticulum (ER) leads to ER stress and then induces ER stress-mediated cell death. The ER stress-mediated cell death is distinctive because the caspase-12 activity plays a crucial role in the progression of cell death. We previously showed that nerve growth factor (NGF) attenuated ER stress-mediated cell death in non-neuronal PC12 cells. Here, we report that BDNF suppressed the ER stress-mediated cell death in tunicamycin (Tm)-treated cerebral cortical neurons. An analysis using a specific inhibitor of phosphatidylinositol 3-kinase (PI3-K), LY294002, revealed that BDNF prevented this cell death via the PI3-K signaling pathway. We found that the number of NeuN/TUNEL-double positive cells and the activity of caspase-3 suppressed by BDNF were increased by LY294002. We also discovered that LY294002 diminished the effect of BDNF on the activation of caspase-12, indicating that BDNF prevents ER stress-mediated cell death via a PI3-K-dependent mechanism by suppressing the activation of caspase-12 in cultured CNS neurons.     

Vascular endothelial growth factor-A, vascular endothelial growth factor receptor-2 and angiopoietin-2 expression in the mouse choroid plexuses

In this study, for the first time, we investigated about the localization of VEGF-A, VEGFR-2 and Ang-2 in the choroid plexuses of the adult mouse by Western blot and immunohistochemistry. Results showed that VEGF-A stained epithelial cells, while anti-VEGFR-2 and -Ang-2 antibodies stained endothelial cells. These data suggest that Ang-2, converting blood vessels into a more plastic and immature phenotype, would provide more accessibility of VEGF-A to endothelial cells.     

Brain-derived neurotrophic factor mRNA and protein in the piglet brainstem and effects of Intermittent Hypercapnic Hypoxia

Brain-derived neurotrophic factor (BDNF) is a neurotrophin essential for the development of normal respiratory rhythm and ventilatory control. Chronic exposure to Intermittent Hypercapnic Hypoxia (IHH) has been shown to alter ventilatory responses of piglets. This study investigated changes in BDNF distribution and expression in seven nuclei of the caudal medulla, from piglets exposed to IHH for 1, 2, 3, or 4 days before death, using non-radioactive in situ hybridisation (for mRNA) and immunohistochemistry (for protein). Compared to controls, BDNF mRNA was markedly increased across the entire medulla of the brainstem, after all durations of IHH (1-4 days). In contrast, BDNF protein expression increased after 1 day of exposure to IHH (p=0.003), but, thereafter, was not different to controls. Amongst individual nuclei, neurons of the dorsal motor nucleus of the vagus (DMNV) showed increased BDNF mRNA (p<0.01), but decreased protein expression (p=0.05) after all durations of IHH. In the ION, both mRNA and protein for BDNF were significantly increased after 1 day IHH (p<0.01 and p=0.001, respectively), but these increases were not sustained. This study is the first to investigate changes in BDNF expression in response to environmental challenges during postnatal development in the brainstem. Implications of the wide distribution of BDNF in the piglet caudal medulla and increased expression after IHH exposure are discussed, with particular reference to roles for BDNF-dependent neurons at this stage of development.     

Neurturin, persephin, and artemin in the human pre- and full-term newborn and adult hippocampus and fascia dentata

The immunochemical occurrence and localization of the Glial cell line-derived neurotrophic factor (GDNF) family ligands neurturin (NTN), persephin (PSP), and artemin (ART) is described in the human postmortem hippocampus and fascia dentata from subjects aged 21 weeks of gestation to 88 years. The detectability of NTN, PSP, and ART is shown in the rat by Western blot and immunohistochemistry up to 70 h postmortem. In the human tissue, labeled neuronal perikarya were detectable for each trophin at all examined ages, with prevalent localization in the pyramidal layer of the Ammon's horn and hilus and granular layer of the fascia dentata. In the adult subjects, punctate elements were also present. Comparison of the pattern of immunoreactive structures among young and adult subjects suggests that intracellular distribution and/or trafficking of the GDNF family ligands may undergo age-related changes. Labeled glial elements were also identifiable. Western blot analysis indicates that the availability of the dimeric and monomeric forms of the trophins may vary with age and postmortem delay. The results obtained suggest the involvement of NTN, PSP, and ART in processes subserving both the organization of this cortical region during development and the functional activity and maintenance of the mature human hippocampal neurons.     

Exercise increased BDNF and trkB in the contralateral hemisphere of the ischemic rat brain

Previous studies have suggested that brain-derived neurotrophic factor (BDNF) and trkB both have a role in plasticity following brain insults and exercise increases BDNF and trkB mRNA levels in the normal brain. We attempted to determine whether treadmill exercise improves motor function following experimental cerebral ischemia, and whether motor outcome is associated with BDNF and trkB expression. We subjected adult male Sprague-Dawley rats to a permanent ischemia, followed by either 12 days of treadmill exercise or non-exercise. In the exercise group, improvements in the motor behavior index were found and BDNF and trkB proteins in contralateral hemisphere were increased. This study suggests that after permanent brain ischemia, exercise improves motor performance and elevates BDNF and trkB proteins in the contralateral hemisphere.     

Brain-derived neurotrophic factor facilitates glutamate and inhibits GABA release from hippocampal synaptosomes through different mechanisms

Brain-derived neurotrophic factor (BDNF) has an acute excitatory effect on rat hippocampal synaptic transmission. To compare the action of BDNF upon the release of excitatory and inhibitory neurotransmitters in the hippocampus, we studied the effect of acutely applied BDNF on the K+-evoked glutamate and on the K+-evoked gamma-aminobutyric acid (GABA) release from rat hippocampal nerve terminals (synaptosomes). The acute application of BDNF (30-100 ng/ml) enhanced the K+-evoked [3H]glutamate release. This effect involved tyrosine-kinase B (TrkB) receptor phosphorylation and Ca2+ entry into synaptosomes through voltage-sensitive calcium channels, since it was abolished by K252a (200 nM), which prevents TrkB-mediated phosphorylation, and by CdCl2 (0.2 mM), a blocker of voltage-sensitive calcium channels. In contrast, BDNF (3-100 ng/ml) inhibited K+-evoked [3H]GABA release from hippocampal synaptosomes. This action was also mediated by phosphorylation of the TrkB receptor, but was independent of Ca2+ entry into synaptosomes through voltage-sensitive calcium channels. Blockade of transport of GABA with SKF 89976a (20 microM) prevented the inhibitory action of BDNF upon GABA release, indicating that BDNF influences the activity of GABA transporters. It is concluded that BDNF influences in an opposite way, through distinct mechanisms, the release of glutamate and the release of GABA from hippocampal synaptosomes.     

Effects of prenatal alcohol exposure on brain-derived neurotrophic factor and its receptor tyrosine kinase B in offspring

Prenatal alcohol exposure produces many developmental defects in the central nervous system. The underlying molecular mechanism, however, has not been fully understood. The present study was undertaken to examine the effects of prenatal alcohol exposure on brain-derived neurotrophic factor (BDNF) and its receptor tyrosine kinase B (TrkB) in offspring. The pregnant Sprague-Dawley rats received 1 or 3 g/kg of alcohol or an isocaloric solution by intragastric intubation once a day from gestational day (GD) 5 to GD 20. On postnatal day 7-8, pups were killed and the hippocampus, striatum, cortex, and cerebellum dissected out. Levels of BDNF mRNA and proteins, total TrkB proteins and receptor phosphorylation were measured. The results showed that prenatal alcohol exposure at the dose of 1 g/kg/day did not significantly affect BDNF protein levels in any region examined. However, administration of alcohol at the dose of 3 g/kg/day markedly reduced levels of BDNF protein and mRNA in the cortex and hippocampus of offspring. Western blotting showed that prenatal alcohol exposure at the dose of 3 g/kg/day also inhibited TrkB phosphorylation in the hippocampus although no changes in total TrkB protein levels were observed in any region examined. Our data suggest that prenatal alcohol exposure alters both presynaptic and postsynaptic BDNF function in certain brain areas of offspring. These alterations in BDNF function may contribute to the development of alcohol-related birth defects.     

Combination of bone marrow mesenchymal stem cells and brain-derived neurotrophic factor for treating spinal cord injury

BACKGROUND:Because bone marrow mesenchymal stem cells (BMSCs) do not secrete sufficient brain-derived neurotrophic factor (BDNF), the use of exogenous BDNF could improve microenvironments in injured regions for BMSCs differentiation. OBJECTIVE:To analyze recovery of the injured spinal cord following BMSCs venous transplantation in combination with consecutive injections of BDNF. DESIGN, TIME AND SETTING:A randomized, controlled animal experiment was performed at the Central Laboratory of First Hospital and Anatomical Laboratory, Fujian Medical University from October 2004 to May 2006.MATERIALS:Human BDNF was purchased from Sigma, USA. METHODS:A total of 44 New Zealand rabbits were randomly assigned to model (n = 8), BDNF (n = 12), BMSC (n = 12), and BMSC+BDNF (n = 12) groups. Spinal cord (L2) injury was established with the dropping method. The model group rabbits were injected with 1 mL normal saline via the ear margin vein; the BDNF group was subdurally injected with 100 μg/d human BDNF for 1 week; the BMSC group was injected with 1 mL BMSCs suspension (2 × 106/mL) via the ear margin vein; and the BMSC+BDNF group rabbits were subdurally injected with 100 μg/d BDNF for 1 week, in addition to BMSCs suspension via the ear margin vein. MAIN OUTCOME MEASURES:BMSCs surface markers were detected by flow cytometry. BMSCs differentiation in the injured spinal cord was detected by immunofluorescence histochemistry. Functional and structural recovery, as well as morphological changes, in the injured spinal cord were respectively detected by Tarlov score, horseradish peroxidase retrograde tracing, and hematoxylin & eosin staining methods at 1, 3, and 5 weeks following transplantation. RESULTS:Transplanted BMSCs differentiated into neuronal-like cells in the injured spinal cord at 3 and 5 weeks following transplantation. Neurological function and pathological damage improved following BMSC + BDNF treatment compared with BDNF or BMSC alone (P < 0.01 or P < 0.05). CONCLUSION:BMSCs venous transplantation in combination with BDNF subdural injection benefits neuronal-like cell differentiation and significantly improves structural and function of injured spinal cord compared with BMSCs or BDNF alone.     

Gastrodin promotes the secretion of brain-derived neurotrophic factor in the injured spinal cord

Gastrodin, an active component of tall gastrodia tuber, is widely used in the treatment of dizziness, paralysis, epilepsy, stroke and dementia, and exhibits a neuroprotective effect. A rat model of spinal cord injury was established using Allen’s method, and gastrodin was administered via the subarachnoid cavity and by intraperitoneal injection for 7 days. Results show that gastrodin promoted the secretion of brain-derived neurotrophic factor in rats with spinal cord injury. After gastrodin treatment, the maximum angle of the inclined plane test, and the Basso, Beattie and Bresnahan scores increased. Moreover, gastrodin improved neural tissue recovery in the injured spinal cord. These results demonstrate that gastrodin promotes the secretion of brain-derived neurotrophic factor, contributes to the recovery of neurological function, and protects neural cells against injury.     

GDNF family ligands display distinct action profiles on cultured GABAergic and serotonergic neurons of rat ventral mesencephalon

Glial-cell-line-derived neurotrophic factor (GDNF), neurturin (NRTN), artemin (ARTN) and persephin (PSPN), known as the GDNF family ligands (GFLs), influence the development, survival and differentiation of cultured dopaminergic neurons from ventral mesencephalon (VM). Detailed knowledge about the effects of GFLs on other neuronal populations in the VM is essential for their potential application as therapeutic molecules for Parkinson's disease. Hence, in a comparative study, we investigated the effects of GFLs on cell densities and morphological differentiation of gamma-aminobutyric acid-immunoreactive (GABA-ir) and serotonin-ir (5-HT-ir) neurons in primary cultures of E14 rat VM. We observed that all GFLs [10 ng/ml] significantly increased GABA-ir cell densities (1.6-fold) as well as neurite length/neuron. However, only GDNF significantly increased the number of primary neurites/neuron, and none of the GFLs affected soma size of GABA-ir neurons. In contrast, only NRTN treatment significantly increased 5-HT-ir cells densities at 10 ng/ml (1.3-fold), while an augmentation was seen for GDNF and PSPN at 100 ng/ml (2.4-fold and 1.7-fold, respectively). ARTN had no effect on 5-HT-ir cell densities. Morphological analysis of 5-HT-ir neurons revealed a significant increase of soma size, number of primary neurites/neuron and neurite length/neuron after GDNF exposure, while PSPN only affected soma size, and NRTN and ARTN failed to exert any effect. In conclusion, we identified GFLs as effective neurotrophic factors for VM GABAergic and serotonergic neurons, demonstrating characteristic individual action profiles emphasizing their important and distinct roles during brain development.     

Heat shock induces neurite outgrowth in PC12m3 cells via the p38 mitogen-activated protein kinase pathway

We investigated the role of the p38 mitogen-activated protein kinase (MAPK) pathway in heat-shock-induced neurite outgrowth of PC12 mutant cells in which nerve growth factor (NGF)-induced neurite outgrowth is impaired. When cultures of the PC12 mutant (PC12m3) cells were exposed to heat stress at 44 degrees C for 10 min, activity of p38 MAPK increased and neurite outgrowth was greatly enhanced. The neurite extension was inhibited by the p38 MAPK inhibitor BS203580. Longer heat treatment of PC12m3 cells provoked cell death, which was enhanced by SB203580. These findings suggest that heat-induced activation of p38 MAPK is responsible for the neurite outgrowth and survival of PC12m3 cells.     

GM1 and ERK signaling in the aged brain

We investigated the ability of GM1 to induce phosphorylation/activation of the extracellular-regulated protein kinases (ERKs) in the striatum, hippocampus and frontal cortex of aged male Sprague-Dawley rats. Three different treatment paradigms were used: a single application of GM1 to brain slices in situ, a single intracerebroventricular (icv) administration of GM1 in vivo, and chronic administration of GM1 in vivo. In situ, GM1 induced a rapid and transient activation of ERK1 and ERK 2 in both young and aged rats, and a similar effect was observed after stimulation with the neurotrophins NGF and BDNF. The aged brain appeared to respond more robustly to neurotrophic stimulation with the pERK2 response being significantly greater in the hippocampus and frontal cortex. Acute icv administration of GM1 resulted in short-lasting phosphorylation of ERKs in both aged groups, while chronic administration of GM1 induced a protracted phosphorylation of ERKs. Following chronic GM1 treatment, pERK2 levels in the aged hippocampus were elevated over young control animals. In agreement with reports that GM1 phosphorylates TrkA in vitro or in situ, treatment with GM1 increased the phosphorylation of TrkA in hippocampus of both young and aged animals. These observations indicate that the aged brain maintains the ability to respond to neurotrophic stimuli and put forward the proposition that the ERK cascade is associated with the action(s) of GM1 ganglioside in vivo.     

AAV2/5-mediated NGF gene delivery protects septal cholinergic neurons following axotomy

Nerve growth factor (NGF) therapy has been proposed to treat cognitive impairments in aged patients including those with Alzheimer's disease. Various viral vectors, including adeno-associated virus serotype 2 (AAV2), have been investigated for their ability to deliver NGF in brain. In this study, hybrid vectors (AAV2/5) consisting of the genome of recombinant AAV2 and the capsid of AAV serotype 5 were evaluated for their ability to deliver NGF and green fluorescent protein (GFP) genes into brain. Compared to AAV2, AAV2/5 consistently led to more septal neurons being transduced with GFP over a wider range of distribution. However, both types of vector provided similar levels of long-term (17 weeks) protection of septal cholinergic neurons from axotomy and led to similar levels of NGF accumulation in this region. These results demonstrate that rAAV-mediated NGF gene delivery is neuroprotective for an extended period of time, but that factors other than transduction efficiency appear to determine transgenic NGF expression in septum.     

Polyethylenimine-mediated NGF gene delivery protects transected septal cholinergic neurons

Polyethylenimine (PEI) is an effective vehicle for in vivo gene delivery in many tissues including brain. PEI mediates transgene expression in brain neurons and glia. To investigate whether PEI-mediated nerve growth factor (NGF) gene transfer protected axotomized septal cholinergic neurons, we injected linear PEI (in vivo jetPEI, Qbiogene) complexed with a plasmid encoding for mouse NGF (PEI/pNGF-W) into the rat septum. PEI complexed with a plasmid encoding for green fluorescent protein (PEI/pGFP) was used as the control. PEI-mediated gene expression was predominantly neuronal. Fimbria-fornix transections (FFTs), conducted 1 day after rats were injected with control vector, resulted in a 70% loss of septal cholinergic neurons. In contrast, PEI/pNGF-W injection prior to FFTs attenuated the loss of septal cholinergic neurons. This is the first study, to our knowledge, that shows the neuroprotective effects induced by PEI-mediated trophic factor gene transfer in brain.     

Region-specific alterations in insulin-like growth factor-I receptor in the central nervous system of nNOS knockout mice

In the present study, we investigated layer-specific changes in insulin-like growth factor-I (IGF-I) receptor localization in the cerebral cortex, hippocampus and cerebellum of neuronal nitric oxide synthase knockout (nNOS-/-) mice using immunohistochemistry. In the cerebral cortex of control mice, moderately stained cells were seen through the layers II-VI in several cortical regions. In nNOS-/- mice, there was a significant decrease in IGF-I receptor immunoreactivity in the same cortical regions. In the hippocampus of control mice, a distinct immunoreactivity pattern was observed in the CA1-3 areas and dentate gyrus. The immunoreactivity for IGF-I receptor was differentially decreased in each layer in nNOS-/- mice. In nNOS-/- cerebellum, IGF-I receptor immunoreactivity was also significantly decreased in each layer of cerebellar cortex and cerebellar nuclei. To clarify whether decreased expression of IGF-I receptor in nNOS-/- mice was specific, the expression of other receptors for IGF-I was also evaluated. Receptor tyrosine kinase type A (TrkA receptor) and TrkB receptor were differentially decreased in each layer of the hippocampus or cerebellum of nNOS-/- mice. Although further studies of functional features of IGF-I systems in the nNOS-/- mice are required, our first morphological data may provide insights into NO-induced changes in trophic support as well as basic knowledge required for the study of NO-associated neurological diseases.     

A neuroprotective role of glial cell line-derived neurotrophic factor following moderate spinal cord contusion injury

The present study investigated neuroprotective effects of glial cell line-derived neurotrophic factor (GDNF), a distant member of the transforming growth factor-beta (TGF-beta) superfamily, following moderate contusive spinal cord injury (SCI) in adult rats. A T11 spinal cord contusion injury was made using an Infinite Horizon impactor (IH; impact force=150 kDyn) and recombinant human GDNF at two concentrations (rhGDNF; 1 or 5 microg/microl), or saline vehicle was delivered intrathecally for 28 days using an Alzet miniosmotic pump. We demonstrated that, at 7 weeks postinjury, GDNF infusion significantly reduced the total lesion volume by 34-42% (assessed stereologically) and increased the percentage of white matter sparing by 10-13% (measured at the injury epicenter), as compared to the vehicle infusion. Retrograde tracing revealed that GDNF infusion resulted in a significant increase in the number of FluoroGold (FG)-labeled neurons in propriospinal regions as well as in two supraspinal regions, that is, the medullary and pontine reticular formation, and the lateral vestibular nucleus. Immunofluorescent staining confirmed that the spared white matter contained neurofilament-positive axons. However, transcranial magnetic motor-evoked potential (tcMMEP) assessment revealed no significant difference in onset latency and amplitude between the GDNF- and vehicle-infused groups. These results suggest that GDNF has a strong neuroprotective effect on white matter sparing and the sparing of a subset of proprio- and supraspinal axons following injury. However, a return of tcMMEPs requires the sparing and/or myelination of axons in a defined region of the white matter which was either not spared or remyelinated at this level of injury severity.     

Increased expression of brain-derived neurotrophic factor but not neurotrophin-3 mRNA in rat brain after cortical impact injury

Levels of brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT3) mRNA expression were measured in a rodent model of traumatic brain injury (TBI) following unilateral injury to the cerebral cortex. To obtain reliable data on the co-expression of neurotrophin genes, adjacent coronal sections from the same rat brains were hybridized in situ with BDNF and NT3 cRNA probes. BDNF mRNA increased at 1, 3, and 5 hr after unilateral cortical injury in the cortex ipsilateral to the injury site and bilaterally in the dorsal hippocampus. NT3 mRNA did not change significantly following injury. Our results suggest that TBI produces rapid increases in BDNF mRNA expression in rat brain without changes in NT3 mRNA expression, a finding which differs from studies of ischemia and seizures. It is possible that increased levels of BDNF mRNA rather than NT3 are important components of pathophysiological responses to TBI. © 1996 Wiley-Liss, Inc.     

Glial cell line-derived neurotrophic factor-enriched bridging transplants promote propriospinal axonal regeneration and enhance myelination after spinal cord injury

Glial cell line-derived neurotrophic factor (GDNF), a distant member of the transforming growth factor-beta (TGF-beta) family, is widely expressed in the developing and adult central nervous system (CNS). At present, limited information is available regarding the effects of GDNF in the repair of spinal cord injury (SCI). In the present study, mini-guidance channels containing either: (1) Matrigel (MG, a basement membrane component), (2) Schwann cells (SCs, 120 x 10(6)/ml) in MG (SC-MG), (3) recombinant human GDNF (rhGDNF, 3 microg/microl) in MG (GDNF-MG), and (4) a combination of all three components (GDNF-SC-MG) were grafted into a T9 hemisection-gap lesion in adult rats to examine the effects of GDNF on axonal regeneration and myelination following SCI. Thirty days post-transplantation, limited axonal growth was observed within guidance channels containing MG-alone (MG). When SCs were added to the channels (SC-MG group), consistent axonal ingrowth containing both myelinated and unmyelinated axons was observed, confirming our previous findings. The addition of GDNF-alone without SCs (GDNF-MG) resulted in substantial ingrowth of unmyelinated axons, suggesting that GDNF has a direct neurite-growth promoting effect on these axons. Implantation of channels containing both GDNF and SCs (GDNF-SC-MG) produced a significant and synergistic increase in axonal regeneration and myelination. In addition, GDNF reduced the extent of reactive gliosis, infiltration of activated macrophages/microglia, and cystic cavitation at the graft-host interfaces. Retrograde tracing revealed that grafts of SC-seeded channels containing GDNF promoted a significant increase in the number of propriospinal neurons which had regenerated their axons into the grafts, as compared to SC-MG-seeded channels. These results indicate that GDNF may play a novel therapeutic role in promoting propriospinal axonal regeneration, enhancing myelin formation, and improving graft-host interfaces after SCI.     

Changes in brain-derived neurotrophic factor expression after transplanting microencapsulated sciatic nerve cells of rabbits into injured spinal cord of rats

BACKGROUND: Changes of brain-derived neurotrophic factor (BDNF) expression reflect function of nerve cells; meanwhile, they play a significant role in researching interventions on plerosis of nerve injury. OBJECTIVE: To observe and compare the effects on changes of BDNF expression in rats with spinal cord injury between microencapsulated sciatic nerve cells of rabbits and only transplanting sciatic nerve cells of rabbits. DESIGN: Randomized controlled animal study. SETTING: Medical School of Jiujiang College. MATERIALS: The experiment was carried out in the Medical Science Researching Center, Jiujiang College from May 2004 to May 2006. A total of 90 healthy adult SD rats, weighing 250–300 g, of either gender; and 10 rabbits, weighing 2.0–2.5 kg, of either gender, were provided by Jiangxi Experimental Animal Center. METHODS: Sciatic nerve tissue of rabbits was separated to make cell suspension. After centrifugation, suspension was mixed with 15 g/L alginate saline solution and ejaculated to 20 mmol/L barium chloride saline solution by double-cavity ejaculator. The obtained cell microcapsules were suspended in saline. Rats were randomly divided into microencapsulated group, only suspension group, and only injured group with 30 animals in each group. After anesthesia, T10 spinous process and vertebra lamina of rats in the former two groups were exposed. Spinal cord tissue in 2-mm length was removed from rats by spinal cord right hemi-section. The gelatin sponges with the size of 2 mm × 2 mm × 2 mm were grafted as filing cage, and absorbed 10 μL microencapsulated sciatic nerve cells of rabbit in the microencapsulated group and 10 μL sciatic nerve cells of rabbits in the only suspension group; respectively. No graft was placed in the only injured group. MAIN OUTCOME MEASURES: On the 1st, 3rd, 7th, 14th and 28th days after operation, immunohistochemistry (SABC technique) was used to detect distribution and amount of positive-reactive neurons in BDNF of spinal cord samples which were selected as 2 cm away from the injured surface. RESULTS: All the 90 rats were involved in the final analysis. Masses of brown-yellow particles were found in the microencapsulated group, and most of them were distributed in the spinal cord anterior horn neurons and glial cells. The positive-reactive neuron particles were also found in the white matter and gray matter. On the 3rd, 7th, 14th and 28th days after operation, amount of positive-reactive neurons in BDNF in the microencapsulated group was higher than that in the only injured group (P < 0.01) and only suspension group (P < 0.05). CONCLUSION: After transplanting microencapsulated nerve cell suspension into injured spinal cord of rats, distribution and amount of positive-reactive neurons in BDNF of local samples at injured surface are increased remarkably as compared with those by using tissue cell transplantation.