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1.
Xiaoguang Chen Yi Li Lei Wang Mark Katakowski Lijie Zhang Jieli Chen Yongxian Xu Subhash C. Gautam Michael Chopp 《Neuropathology》2002,22(4):275-279
Intravenous administration of human bone marrow stromal cells (hMSCs) after middle cerebral artery occlusion (MCAo) in rats provides functional benefit. We tested the hypothesis that these functional benefits are derived in part from hMSC production of growth and trophic factors. Quantitative sandwich enzyme‐linked immunosorbent assay (ELISA) of hMSCs cultured with normal and MCAo brain extracts were performed. hMSCs cultured in supernatant derived from ischemic brain extracts increased production of brain‐derived neurotrophic factor (BDNF), nerve growth factor (NGF), vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF). These neurotrophins and angiogenic growth factors increased in a post‐ischemia time‐dependent manner. The hMSC capacity to increase expression of growth and trophic factors may be the key to the benefit provided by transplanted hMSCs in the ischemic brain. 相似文献
2.
Theodore A. Henderson Robert W. Rhoades Carol A. Bennett-Clarke Pat A. Osborne Eugene M. Johnson Mark F. Jacquin 《The Journal of comparative neurology》1993,336(2):243-260
Prior studies indicate that neonatal nerve injury kills many trigeminal (V) first- and second-order cells, and interrupts pattern formation in the brainstem and cerebral cortex. Yet it is not known whether effects upon cell survival and pattern formation are causally related. To determine whether axotomized V ganglion cells can be rescued by an exogenous trophic agent, rats received 5 mg/kg of nerve growth factor (NGF) prior to, and every day after, infraorbital nerve section on the day of birth until sacrifice on postnatal day (PND) 1, 3, 5, 7, or 14. Other animals received identical lesions without NGF. Ganglion cell numbers were significantly reduced by PNDl in pups not given NGF, while NGF-treated rats displayed no significant cell loss through PND7. However, NGF did not permanently rescue V neurons because ganglion cell numbers were reliably reduced by PND14. Cell numbers in V nucleus principalis were reduced by PNDl in pups not given NGF, while NGF-treated animals displayed no cell loss through PND14. NGF's rescue of second-order cells is probably an indirect effect of NGF actions upon V ganglion cells because, in other newborns, NGF failed to maintain principalis cells after direct lesion of the left V ganglion. To determine whether preventing cell death permits whisker-related pattern formation, other rats also received NGF prior to and after infraorbital nerve section at birth. After 3–14 days, patterns were assessed in the brainstem and cortex with cytochrome oxidase histochemistry and serotonin immunocytochemistry. Whisker-related patterns failed to develop as in cases not given NGF. These data indicate that communication with the periphery is necessary for the maintenance of central whisker-related patterns. They also suggest that V ganglion cells can be rescued, albeit temporarily, from rapid injury-induced death by NGF, thereby delaying injury-induced cell death in nucleus principalis. However, the mechanism(s) responsible for injury-induced pattern alterations in the developing V system remains to be elucidated. © 1993 Wiley-Liss, Inc. 相似文献
3.
Dominici Carlo Nicotra Maria Rita Alemaà Stefano Bosman Cesare Castello Manuel A. Donfrancesco Alberto Gallo Pietro Natali Pier Giorgio 《Journal of neuro-oncology》1997,31(1-2):57-64
In neuroblastoma, high levels of mRNA for p14h
trkA
and p75
LNGFR
neurotrophin receptors are predictive of favorable outcome. Their evaluation by Northern blot, however, requires substantial amounts of tissue and this prevents their routine evaluation as well as the possibility for multicenter studies to be easily carried out. In an attempt to overcome these limitations, the feasibility and reliability of determining both neurotrophin receptors on cryostat sections by immunohistochemistry were assessed, and these findings were compared to those obtained from Northern blot analysis. Primary tumor samples from 28 untreated patients at all stages were evaluated by using H10 anti-p140
trkA
and ME20.4 anti-p75
LNGFR
mAbs. Although weak, positiveimmunostaining was found in 9 of 28 tumors for p140
trkA
and in 5 of 28 tumors for p75
LNGFR
. As compared to Northern blot, the concordance rate was 79% (22 of 28 cases) for p140
trkA
(p < 0.05) and 71% (20 of 28 cases) for p75
LNGFR
(p < 0.05). No case negative for Northern blot was found to be positive with immunohistochemistry. Since only high mRNA levels for both receptors have been shown to be clinically relevant, their immunohistochemical detection, although less sensitive than Northern blot, can be just as sufficient and reliable as a prognostic tool, and possibly with a better cost-benefit ratio. 相似文献
4.
Cultured spinal cord motoneurons from day 15 rat embryos (E15) represent a useful model to study Ca2+ channel diversities and their regulation by neurotrophins. Besides the previously identified L-, N- and P-type channels, E15 rat motoneurons also express high densities of R-type channels. We have previously shown that the P-type channel is nearly absent in 60% of these cells, while the R-type contributes to approximately 35% of the total current. Here, we show that chronic preincubation of cultured rat motoneurons with high concentrations (20-100 ng/mL) of brain-derived neurotrophic factor (BDNF) caused a selective up-regulation of the P- and R-type current density available after blocking N- and L-type channels, with no changes to cell membrane capacitance. N- and L-type channels were either not affected or slightly down-modulated by the neurotrophin. The onset of BDNF up-regulation of P/R-type currents had a half-time of 12 h and reached maximal values of approximately 80%. High concentrations of nerve growth factor (NGF; 50-100 ng/mL) had no effect on P/R currents, while BDNF action was prevented by the kinase inhibitor K252a and by the protein synthesis inhibitor anisomycin. These results suggest that chronic applications of BDNF selectively up-regulates the Ca2+ channel types which are most likely to be involved in the control of neurotransmitter release in mammalian neuromuscular junctions. The signal transduction mechanism is probably mediated by TrkB receptors and involves the synthesis of newly functionally active P- and R-type channels. Our data furnish a rationale for a number of recent observations in other laboratories, in which prolonged applications of neurotrophins were shown to potentiate the presynaptic response in developing synapses. 相似文献
5.
R. A. Hill 《Journal of neuroendocrinology》2012,24(12):1553-1561
Sex steroid hormones and neurotrophic factors are involved in pruning and shaping the developing brain and have been implicated in the pathogenesis of neurodevelopmental disorders. Sex steroid hormones are also involved in the regulation of brain‐derived neurotrophic factor expression. A review of the literature is provided on the relationship between brain‐derived neurotrophic factor and sex steroid hormones, as well as the mechanisms behind this interaction, in the context of how this relationship may be involved in the development of neurodevelopmental psychiatric illnesses, such as schizophrenia and depression. 相似文献
6.
Nicolas Guyon Leonardo Rakauskas Zacharias Josina Anna van Lunteren Jana Immenschuh Janos Fuzik Antje Mrtin Yang Xuan Misha Zilberter Hoseok Kim Konstantinos Meletis Cleiton Lopes-Aguiar Marie Carln 《The Journal of neuroscience》2021,41(14):3120
Inhibitory interneurons expressing parvalbumin (PV) are central to cortical network dynamics, generation of γ oscillations, and cognition. Dysfunction of PV interneurons disrupts cortical information processing and cognitive behavior. Brain-derived neurotrophic factor (BDNF)/tyrosine receptor kinase B (trkB) signaling regulates the maturation of cortical PV interneurons but is also implicated in their adult multidimensional functions. Using a novel viral strategy for cell-type-specific and spatially restricted expression of a dominant-negative trkB (trkB.DN), we show that BDNF/trkB signaling is essential to the integrity and maintenance of prefrontal PV interneurons in adult male and female mice. Reduced BDNF/trkB signaling in PV interneurons in the medial prefrontal cortex (mPFC) resulted in deficient PV inhibition and increased baseline local field potential (LFP) activity in a broad frequency band. The altered network activity was particularly pronounced during increased activation of the prefrontal network and was associated with changed dynamics of local excitatory neurons, as well as decreased modulation of the LFP, abnormalities that appeared to generalize across stimuli and brain states. In addition, our findings link reduced BDNF/trkB signaling in prefrontal PV interneurons to increased aggression. Together our investigations demonstrate that BDNF/trkB signaling in PV interneurons in the adult mPFC is essential to local network dynamics and cognitive behavior. Our data provide direct support for the suggested association between decreased trkB signaling, deficient PV inhibition, and altered prefrontal circuitry.SIGNIFICANCE STATEMENT Brain-derived neurotrophic factor (BDNF)/tyrosine receptor kinase B (trkB) signaling promotes the maturation of inhibitory parvalbumin (PV) interneurons, neurons central to local cortical dynamics, γ rhythms, and cognition. Here, we used a novel viral approach for reduced BDNF/trkB signaling in PV interneurons in the medial prefrontal cortex (mPFC) to establish the role of BDNF/trkB signaling in adult prefrontal network activities. Reduced BDNF/trkB signaling caused pronounced morphologic alterations, reduced PV inhibition, and deficient prefrontal network dynamics. The altered network activity appeared to manifest across stimuli and brain states and was associated with aberrant local field potential (LFP) activities and increased aggression. The results demonstrate that adult BDNF/trkB signaling is essential to PV inhibition and prefrontal circuit function and directly links BDNF/trkB signaling to network integrity in the adult brain. 相似文献
7.
BACKGROUND: Neuropathic pain is common in diabetic patients. Degeneration of sensory C-fibers in peripheral nerve plays a prominent role in the generation of neuropathic pain. We examined degenerative changes of C-fibers in two rat models with type 1 and type 2 diabetes. METHODS: Type 1 insulinopenic BB/Wor and type 2 hyperinsulinemic diabetic BBZDR/Wor-rats of 8 months duration with equal exposure to hyperglycemia were examined. Thermal hyperalgesia was monitored using an infrared thermal probe. C-fiber size, number, frequencies of denervated Schwann cells, regenerating C-fibers, type 2 axon/Schwann cell relationship and collagen pockets in the sural nerve were examined morphometrically. Neurotrophic receptor expression was examined by Western blotting. Neurotrophins and neuropeptides were examined by ELISA. RESULTS: Type 1 rats showed increased thermal hyperalgesia followed by a decrease. Hyperalgesia in type 2 rats showed a slower progression. These findings were associated with a 50% (p < 0.001) loss of C-fibers, increased frequencies of denervated Schwann cells (p < 0.001), regenerating fibers (p < 0.001), collagen pockets (p < 0.001) and type 2 axon/Schwann cell relationship (p < 0.001) in type 1, but not in type 2 rats. Expression of insulin receptor, IGF-1R, TrkA and C was decreased in BB/Wor rats, whereas BBZDR/Wor rats showed milder or no deficits. NGF and NT-3 in sciatic nerve and substance P and calcitonin gene-related peptide in dorsal root ganglia were decreased in type 1, but not in type 2 rats. CONCLUSION: The more severe molecular, functional and morphometric abnormalities of nociceptive C-fibers in type 1 insulinopenic rats compared to type 2 hyperinsulinemic rats suggest that impaired insulin action may play a more important pathogenetic role than hyperglycemia per se. 相似文献
8.
《Journal of endodontics》2019,45(6):729-735
IntroductionA plethora of bioactive molecules present during tooth formation become sequestered in the mineralized dentin matrix and can be released into the pulp tissue after demineralization from carious lesions. However, neurotrophic factors are differentially expressed and secreted during various stages of odontogenesis. Thus, the aims of this study were(1) to investigate their presence and relative abundance in crown and root dentin and(2) to evaluate the bioactivity of dentin-derived proteins on neuronal cells.MethodsDentin matrix proteins (DMPs) were isolated from matched roots and crowns of extracted healthy human third molars. The total protein amount as well as the concentration of growth factors and neurotrophic proteins were quantified. The impact on neuritogenesis was determined with mouse trigeminal neurons in vitro and by a hydrogel implant model in vivo. Transient receptor potential cation channel subfamily V member 1 (TRPV1) sensitization of DMP-conditioned neurons was evaluated by single-cell calcium imaging.ResultsThe relative concentration of neurotrophic molecules revealed that nerve growth factor is the most abundant neurotrophin with 3-fold increased expression in radicular dentin. Similarly, brain-derived neurotrophic factor and neurotrophin 3 are more abundant in radicular than coronal dentin. Conversely, glial cell line–derived neurotrophic factor is more abundant in coronal dentin, whereas neurotrophin 4 is equally distributed. Dentin matrix proteins promoted neurite outgrowth in vitro and axonal targeting in vivo, with a greater effect observed by radicular dentin extracts. Furthermore, DMPs sensitized TRPV1 responses in mouse trigeminal neurons with greater activity seen with extracts from root dentin.ConclusionsNeurotrophic factors are differentially distributed between coronal and radicular dentin with different effects of dentin-derived proteins on axonal growth and targeting as well as the sensitization of TRPV1. Thus, extracellular proteins from the dentin matrix are likely involved in neurogenic responses to caries and could be exploited in clinical regenerative endodontics to promote reinnervation and enhance tissue regeneration. 相似文献
9.
Zhaowei Zhu MD PhD Xinhua He PhD Canbin Zheng MD PhD Jian Xu MD PhD Li Jiang PhD Liqiang Gu MD PhD Jiakai Zhu MD PhD Qingtang Zhu MD PhD Xiaolin Liu MD PhD 《Muscle & nerve》2014,50(2):235-243
Introduction: Acellular nerve grafts are good candidates for nerve repair, but the clinical outcome of grafting is not always satisfactory. We investigated whether etifoxine could enhance nerve regeneration. Methods: Seventy‐two Sprague‐Dawley rats were divided into 3 groups: (1) autograft; (2) acellular nerve graft; and (3) acellular nerve graft plus etifoxine. Histological and electrophysiological examinations were performed to evaluate the efficacy of nerve regeneration. Walking‐track analysis was used to examine functional recovery. Quantitative polymerase chain reaction was used to evaluate changes in mRNA level. Results: Etifoxine: (i) increased expression of neurofilaments in regenerated axons; (ii) improved sciatic nerve regeneration measured by histological examination; (iii) increased nerve conduction velocity; (iv) improved walking behavior as measured by footprint analysis; and (v) boosted expression of neurotrophins. Conclusions: These results show that etifoxine can enhance peripheral nerve regeneration across large nerve gaps repaired by acellular nerve grafts by increasing expression of neurotrophins. Muscle Nerve 50:235–243, 2014 相似文献
10.