Role Of Nerve Growth Factor Research Articles

Protective effects and anti-apoptotic role of nerve growth factor on spinal cord neurons in sciatic nerve-injured rats

Objectives:The purpose of this study is to demonstrate a dependence of spinal cord motoneurons on the communication with their targets, sciatic nerves, and investigate whether the effects of nerve growth factor (NGF) on the spinal cord neuron apoptosis and surviving through the regulation of nuclear factor-kappa B (NF-kappaB) in Schwann cells (SCs) in sciatic nerve injured rats.Methods:Ninety healthy adult Sprague–Dawley rats were divided randomly into normal control group, crushing group, and NGF-intervened group. When sciatic nerve crushed 1, 3, 7, 14, and 21 days, the expression of NF-kappaB in SCs and the apoptosis regulator Bcl-2 and Caspase-3 in spinal cord were examined by immunohistochemistry staining, Western blot analysis, and immunofluorescence double-labeling method, the motor neuron apoptosis were investigated by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL), and the surviving neurons were tested by toluidine blue (Nissl) staining, respectively. All the data were further analyzed with SPSS10·0 application software.Results:The level of the expression of NF-kappaB in crushing group enhanced at 1 day after crushing, reached peak at 3 days, and reduced at least until 21 days, which was markedly higher than that in the normal control group. The expression of NF-kappaB in NGF-intervened group showed the same changes, reached peak at 7 days, and reduced until 21 days. However, when compared with crushing group, the expression of NF-kappaB in NGF-intervened group was down-regulated significantly until 3 days after injury, and up-regulated obviously with time going on. The same trend was observed in the time course on motor neuron apoptosis in crushing group and NGF-intervened group after sciatic nerves injury, while the reversing change was found in the surviving neurons. Moreover, the kinetics of Bcl-2 expression in spinal cord was consistent with that of NF-kappaB, while reversing with that of Caspase-3.Conclusion:The findings revealed that NGF may play a pivotal role of anti-apoptosis in spinal cord neurons through retrograde transport of NF-kappaB in SCs following sciatic nerve injury in rats.

Exploring the Role of Nerve Growth Factor in Multiple Sclerosis: Implications in Myelin Repair

Multiple sclerosis (MS) is a chronic disease resulting from targeted destruction of central nervous system (CNS) myelin. MS is suggested to be an autoimmune disease involving the pathogenic activation of CD4(+) T cells by a foreign antigen in the peripheral blood. The activated CD4(+) T cells liberate inflammatory cytokines that facilitate the breakdown of the blood-brain barrier (BBB) promoting their passage into the CNS. Inside the CNS, CD4(+) T cells become re-activated by myelin proteins sharing a similar structure to the foreign antigen that initially triggered the immune response. The CD4(+) T cells continue to liberate inflammatory cytokines, such as tumor necrosis factor α (TNFα), which activates macrophages and antibodies responsible for the phagocytosis of myelin. Acute CNS lesions can be re-myelinated, however, the repair of chronic demyelinating lesions is limited, leading to permanent neurological deficits. Although current MS treatments reduce severity and slow disease progression, they do not directly repair damaged myelin. Henceforth, recent treatment strategies have focused on neurotrophins, such as nerve growth factor (NGF) for myelin repair. NGF promotes axonal regeneration, survival, protection and differentiation of oligodendrocytes (OGs) and facilitates migration and proliferation of oligodendrocyte precursors (OPs) to the sites of myelin damage. NGF also directly regulates key structural proteins that comprise myelin. Interestingly, NGF also induces the production of brain-derived neurotrophic factor (BDNF), another integral neurotrophin involved in myelination. The intricate signaling between neurotrophins and cytokines that governs myelin repair supports the role of NGF as a leading therapeutic candidate in white matter disorders, such as MS.

The role of nerve growth factor and its receptors in tumorigenesis and cancer pain.

The nerve growth factor (NGF) is a growth factor that belongs to the neurotrophin family. NGF has two structurally different receptors, the p75 neurotrophin receptor (p75NTR) and the tropomyosin-related kinase A (TrkA). Interaction of NGF with its receptors regulates a variety of physiological processes of neuronal system. Recent studies have shown that NGF and its receptors were involved in the regulation of tumourigenesis by either supporting or suppressing tumor growth depending on the tumor types. This review summarizes the current views of NGF and its receptors in tumorigenesis and cancer pain.

Role of nerve growth factor and its TRKA receptor in normal ovarian and epithelial ovarian cancer angiogenesis

In normal ovarian function a controlled angiogenesis is essential. Several growth factors are involved in this process, such as the vascular endothelial growth factor (VEGF) and nerve growth factor (NGF). The angiogenesis process in the normal ovary is a tightly controlled process that occurs in each ovarian cycle. Also, angiogenesis is critical for ovarian cancer development and it is responsible for tumor spread, metastasis and its peritoneal dissemination. Ovarian cancer is the fifth leading cause of cancer death in women and it is distinguished as the most lethal gynecologic cancer. In recent years angiogenesis has been given considerable attention in order to identify targets for developing effective anti-tumor therapies. Several molecules have been reported to promote angiogenesis, such as platelet-derived growth factor (PDGF) and its receptors, the angiopoietin/Tie ligand/receptor system and fibroblast growth factor (FGF). Primarily, VEGF has been identified to play key roles in driving angiogenesis. The above-mentioned molecules are candidate drug targets. Used in combination with other treatments, anti-angiogenic therapies have managed to reduce disease progression. The present review is focused in NGF and its high affinity receptor tyrosine kinase A (TRKA). The expression of VEGF, proliferation and the angiogenesis process in ovarian cancer is importantly induced by NGF, among other molecules.

Hippocampal Neuron Protecting Effect of Propofol Against Hypoxia/Reoxygenation via Inducing Nerve Growth Factor

Propofol, an intravenous anesthetic agent, exhibits neuroprotective effects against cerebral ischemia–reperfusion injury. Here, we used a model of Hypoxia/Re-Oxygenation (H/R) injury to examine the hippocampal neuroprotective effect of propofol, and explored the role of Nerve Growth Factor (NGF) and NGF receptor TrkA in this action. Rat hippocampal neuron cells were subjected to H/R with different concentrations propofol, the viability and apoptosis of the cells were then determined by MTT assay and annexin V flow cytometry, respectively. Meanwhile, expression of NGF and TrkA were measured by RT-PCR and Western blot. The results showed that H/R significantly reduced viability and increased apoptosis of cultured hippocampal neuron cells, along with the significantly decreased expressions of NGF and TrkA. However, pretreatment of propofol recovered the expressions of NGF and the receptor TrkA, resulting in significantly decreased H/R-induced neurotoxicity. C-Jun N-terminal kinase (JNK) inhibitor suppressed the effect of propofol on the NGF expression, and the TrkA was decreased by PD98059, the Erk1/2 signal blocker. Administration of TrkA inhibitor altered the neuroprotective effect of propofol. These findings suggested the potential of propofol for protecting hippocampal neuron against H/R through at least partly, NGF/TrkA signaling pathway.

Novel approaches to the post-myocardial infarction/heart failure neural remodeling

The review aims to discuss the role of nerve growth factor (NGF) as a potential novel biomarker in post-myocardial infarction (MI) and in heart failure (HF), with a specific focus on neural remodeling and sprouting processes occurring after tissue damage. Many experimental data show that MI induces nerve sprouting, leading to increased sympathetic outflow and higher risk of ventricular arrhythmias and sudden cardiac death. In this framework, cardiac and circulating NGF might be an indicator of the innervation process and neural remodeling: it dramatically increases after MI, while it declines along with advanced HF and ventricular dysfunction. The bimodal behavior of NGF in acute and chronic settings leads to the speculation that NGF modulation may be a pharmacological target for intervention in different stages of the ischemic heart disease. Specifically, a fascinating possibility is to support or to inhibit NGF receptors, in order to prevent negative cardiac remodeling after MI and consequent ventricular dysfunction.

Hypertrophy of Neurons Within Cardiac Ganglia in Human, Canine, and Rat Heart Failure: The Potential Role of Nerve Growth Factor

BackgroundAutonomic imbalances including parasympathetic withdrawal and sympathetic overactivity are cardinal features of heart failure regardless of etiology; however, mechanisms underlying these imbalances remain unknown. Animal model studies of heart and visceral organ hypertrophy predict that nerve growth factor levels should be elevated in heart failure; whether this is so in human heart failure, though, remains unclear. We tested the hypotheses that neurons in cardiac ganglia are hypertrophied in human, canine, and rat heart failure and that nerve growth factor, which we hypothesize is elevated in the failing heart, contributes to this neuronal hypertrophy.Methods and ResultsSomal morphology of neurons from human (579.54±14.34 versus 327.45±9.17 μm2; P<0.01) and canine hearts (767.80±18.37 versus 650.23±9.84 μm2; P<0.01) failing secondary to ischemia and neurons from spontaneously hypertensive rat hearts (327.98±3.15 versus 271.29±2.79 μm2; P<0.01) failing secondary to hypertension reveal significant hypertrophy of neurons in cardiac ganglia compared with controls. Western blot analysis shows that nerve growth factor levels in the explanted, failing human heart are 250% greater than levels in healthy donor hearts. Neurons from cardiac ganglia cultured with nerve growth factor are significantly larger and have greater dendritic arborization than neurons in control cultures.ConclusionsHypertrophied neurons are significantly less excitable than smaller ones; thus, hypertrophy of vagal postganglionic neurons in cardiac ganglia would help to explain the parasympathetic withdrawal that accompanies heart failure. Furthermore, our observations suggest that nerve growth factor, which is elevated in the failing human heart, causes hypertrophy of neurons in cardiac ganglia.

The Role of Nerve Growth Factor in Neuropathic Pain Inhibition Produced by Resiniferatoxin Treatment in the Dorsal Root Ganglia

Resiniferatoxin (RTX), an excitotoxic agonist for vanilloid receptor 1, is a promising candidate for intractable pain treatment. We evaluated the effects of RTX, applied to dorsal root ganglia (DRG) at high doses (1200 ng), in sensory-motor function and nerve growth factor (NGF) alterations in a photochemical sciatic nerve injury rat model. Following RTX injection into the L3-6 DRG at high doses and behavioral evaluation, the rats were sacrificed and the DRG were tested by immunohistochemistry and mRNA analysis for NGF and its' receptors, tyrosine kinase A (TrkA) and p75. The correlation between neuropathic pain and NGF, TrkA, and p75 expression was analyzed. The treated rats had preserved touch, cold, pain, and high-heat sensations, and exhibited hypoalgesia to low-heat stimulation. After RTX treatment, TrkA and p75 altered their expressions from one neuronal type to another in the DRG. NGF and p75 expression changed from the small-size neurons in neuropathic rat DRG to the large- and medium-size neurons in non-neuropathic and RTX-treated animals, concomitantly with neuropathic pain suppression. TrkA was expressed in the small-size neurons in neuropathic rat DRG, and was drastically reduced in all size neurons after RTX treatment. NGF, TrkA, and p75 mRNA expression supported these phenotypic changes in the DRG. The pathway of NGF-TrkA expressed in the small-size neurons, associated with neuropathic pain, was shifted to the NGF-p75 pathway expressed in the large-size neurons after RTX treatment, in association with neuropathic pain inhibition. These findings may play an important role in clinical trial designs.

Neuroprotective role of nerve growth factor in hypoxic-ischemic brain injury.

Hypoxic-ischemic brain injuries (HIBI) in childhood are frequently associated with poor clinical and neurological outcome. Unfortunately, there is currently no effective therapy to restore neuronal loss and to determine substantial clinical improvement. Several neurotrophins, such as Nerve Growth Factor (NGF), Brain-Derived Neurotrophic Factor (BDNF), and Glial Derived Neurotrophic Factor (GDNF), play a key role in the development, differentiation, and survival of the neurons of the peripheral and central nervous system. Experimental animal studies demonstrated their neuroprotective role in HIBI, while only a few studies examined the neuroprotective mechanisms in patients with severe HIBI. We report two cases of children with HIBI and prolonged comatose state who showed a significant improvement after intraventricular NGF administration characterized by amelioration of electroencephalogram (EEG) and cerebral perfusion at single-photon emission computed tomography (SPECT). The improvement in motor and cognitive functions of these children could be related to the neuroprotective role exerted by NGF in residual viable cholinergic neurons, leading to the restoration of neuronal networks in the damaged brain.

Differential Effects of Dehydroepiandrosterone and Testosterone in Prostate and Colon Cancer Cell Apoptosis: The Role of Nerve Growth Factor (NGF) Receptors

Tumor growth is fostered by inhibition of cell death, which involves the receptiveness of tumor to growth factors and hormones. We have recently shown that testosterone exerts proapoptotic effects in prostate and colon cancer cells through a membrane-initiated mechanism. In addition, we have recently reported that dehydroepiandrosterone (DHEA) can control cell fate, activating nerve growth factor (NGF) receptors, namely tropomyosin-related kinase (Trk)A and p75 neurotrophin receptor, in primary neurons and in PC12 tumoral cells. NGF was recently involved in cancer cell proliferation and apoptosis. In the present study, we explored the cross talk between androgens (testosterone and DHEA) and NGF in regulating apoptosis of prostate and colon cancer cells. DHEA and NGF strongly blunted serum deprivation-induced apoptosis, whereas testosterone induced apoptosis of both cancer cell lines. The antiapoptotic effect of both DHEA and NGF was completely reversed by testosterone. In line with this, DHEA or NGF up-regulated, whereas testosterone down-regulated, the expression of TrkA receptor. The effects of androgens were abolished in both cell lines in the presence of TrkA inhibitor. DHEA induced the phosphorylation of TrkA and the interaction of p75 neurotrophin receptor with its effectors, Rho protein GDP dissociation inhibitor and receptor interacting serine/threonine-protein kinase 2. Conversely, testosterone was unable to activate both receptors. Testosterone acted as a DHEA and NGF antagonist, by blocking the activation of both receptors by DHEA or NGF. Our findings suggest that androgens may influence hormone-sensitive tumor cells via their cross talk with NGF receptors. The interplay between steroid hormone and neurotrophins signaling in hormone-dependent tumors offers new insights in the pathophysiology of these neoplasias.

Sa2063 The Role of Nerve Growth Factor in the Ameliorating Effect of Gastric Electrical Stimulation on Visceral Hypersensitivity

Sa2063 The Role of Nerve Growth Factor in the Ameliorating Effect of Gastric Electrical Stimulation on Visceral Hypersensitivity

Short‐term environmental enrichment, in the absence of exercise, improves memory, and increases NGF concentration, early neuronal survival, and synaptogenesis in the dentate gyrus in a time‐dependent manner

Environmental manipulations can enhance neuroplasticity in the brain, with enrichment-induced cognitive improvements being linked to increased expression of growth factors, such as neurotrophins, and enhanced hippocampal neurogenesis. There is, however, a great deal of variation in environmental enrichment protocols used in the literature, making it difficult to assess the role of particular aspects of enrichment upon memory and the underlying associated mechanisms. This study sought to evaluate the efficacy of environmental enrichment, in the absence of exercise, as a cognitive enhancer and assess the role of Nerve Growth Factor (NGF), neurogenesis and synaptogenesis in this process. We report that rats housed in an enriched environment for 3 and 6 weeks (wk) displayed improved recognition memory, while rats enriched for 6 wk also displayed improved spatial and working memory. Neurochemical analyses revealed significant increases in NGF concentration and subgranular progenitor cell survival (as measured by BrdU+ nuclei) in the dentate gyrus of rats enriched for 6 wk, suggesting that these cellular changes may mediate the enrichment-induced memory improvements. Further analysis revealed a significant positive correlation between recognition task performance and BrdU+ nuclei. In addition, rats enriched for 6 wk showed a significant increase in expression of synaptophysin and synapsin I in the dentate gyrus, indicating that environmental enrichment can increase synaptogenesis. These data indicate a time-dependent cognitive-enhancing effect of environmental enrichment that is independent of physical activity. These data also support a role for increased concentration of NGF in dentate gyrus, synaptogenesis, and neurogenesis in mediating this effect.

Role of nerve growth factor (NGF) and its receptors in folliculogenesis

Summary Nerve growth factor (NGF) is a prototype member of the neurotrophins family and has important functions in the maintenance of viability and proliferation of neuronal and non-neuronal cells, such as certain ovarian cells. The present review highlights the role of NGF and its receptors on ovarian follicle development. NGF initiates its multiple actions through binding to two classes of receptors: the high affinity receptor tyrosine kinase A (TrkA) and the low-affinity receptor p75. Different intracytoplasmic signalling pathways may be activated through binding to NGF due to variation in the receptors. The TrkA receptor activates predominantly phosphatidylinositol-3-kinase (PI3K) and mitogenic activated protein kinase (MAPK) to promote cell survival and proliferation. The activation of the phospholipase type Cγ (PLCγ) pathway, which results in the production of diacylglycerol (DAG) and inositol triphosphate (IP3), culminates in the release of calcium from the intracytoplasmic cellular stocks. However, the details of activation through p75 receptor are less well known. Expression of NGF and its receptors is localized in ovarian cells (oocyte, granulosa, theca and interstitial cells) from several species, which suggests that NGF and its receptors may regulate some ovarian functions such as follicular survival or development. Thus, the use of NGF in culture medium for ovarian follicles may be of critical importance for researchers who want to promote follicular development in vitro in the future.

Nerve growth factor induces cell cycle arrest of astrocytes

Neurotrophins can influence multiple cellular functions depending on the cellular context and the specific receptors they interact with. These neurotrophic factors have been extensively studied for their ability to support neuronal survival via Trk receptors and to induce apoptosis via the p75(NTR). However, the p75(NTR) is also detected on cell populations that do not undergo apoptosis in response to neurotrophins. In particular, the authors have detected p75(NTR) expression on astrocytes during development and after seizure-induced injury. In this study, the authors investigated the role of Nerve growth factor (NGF) in regulating astrocyte proliferation and in influencing specific aspects of the cell cycle. The authors have demonstrated that NGF prevents the induction of cyclins and their association with specific cyclin-dependent kinases, and thereby prevents progression through the G1 phase of the cell cycle. Since the authors have previously shown that p75(NTR) but not TrkA, is expressed in astrocytes, these data suggest that activation of p75(NTR) promotes withdrawal of astrocytes from the cell cycle, which may have important consequences during development and after injury.

The potential role of nerve growth factor in cryoneurolysis-induced neuropathic pain in rats

Cryoanalgesia is suggested as a risk factor of neuropathic pain. The current study investigated the pain behavior of sciatic nerve cryoneurolysis (SCN) in adult male rats. The role of nerve growth factor (NGF) was also studied. The mechanical threshold was significantly elevated in SCN group than sham-operation group within 14days after surgery. After 28days, 22 out of 39 SCN rats (56.4%) represented mechanical hyperalgesia. There were much more NGF-immunoreactive nerve cells expressed in the dorsal horn in SCN rats with hyperalgesia. The NGF protein levels of SCN rats measured by Western blot were higher than sham-operation rats, while they were significantly higher in SCN rats with hyperalgesia than those without hyperalgesia. Pain-related behavior improved after anti-NGF treatment, compared with vehicle control group. NGF is associated with SCN-induced neuropathic pain. Peripherally secreted NGF may play an important role in this mechanism.

Association between Nerve Growth Factor Gene Polymorphism and Executive Dysfunction in Japanese Patients with Early-Stage Alzheimer’s Disease and Amnestic Mild Cognitive Impairment

Background/Aims: To address the clinical neurocognitive roles of nerve growth factor (NGF) genetic polymorphism in early-stage Alzheimer’s disease (AD) and amnestic mild cognitive impairment (A-MCI), we investigated the association between this single-nucleotide polymorphism (SNP) and executive dysfunction as a nonmemory cognitive impairment. Methods: Among 200 outpatients with dementia and MCI whose NGF SNP rs6330 genotype was identified, those with A-MCI (n = 35) and early-stage AD (n = 67) were recruited and divided into three groups according to genotype (C/C: n = 58, C/T: n = 39, T/T: n = 5). Then, the Frontal Assessment Battery (FAB) scores were compared among the three (C/C, C/T, T/T) or two (C/C, T carrier) genotype groups. Results: Among the subtests, a significant difference was only noted for the go/no-go scores (p < 0.01) between C/C and T carriers. However, no significant differences in the demographic variables and other neuropsychological subtest scores reflecting attentional and memory function were observed among the genotypes. Conclusion: Regarding the functional roles of neurotrophin polymorphisms as they relate to executive dysfunction, the NGF gene rs6330 might influence the inhibition task in Japanese patients with early-stage AD or A-MCI.

Tissue repair driven by two different mechanisms of growth factor plasmids VEGF and NGF in mice auricular cartilage: regeneration mediated by administering growth factor plasmids

The focus of this study was to compare the role of nerve growth factor (NGF) and vascular endothelial growth factor (VEGF) in the regeneration of experimental skin and cartilage trauma. The role of VEGF in this process is known since decade; the NGF participation on this process has been first discussed within the spinal cord injury repair. We hypothesized that both VEGF and NGF induce angiogenesis and take part on the repair process. The angiogenesis response and the cartilage regeneration after phVEGF(165) plasmid and rat pcNGF plasmid administration were investigated using BALB/c mice. PhVEGF(165) and pcNFG were injected into the right mice ear and plain vector injection into the left ear the day before trauma. The next day, all mice were ear-punched, resulting in 2-mm diameter puncture through the center of both pinnae. In BALB/c mouse strain, a significantly faster cartilage repair was observed after phVEGF(165) and pcNGF injection into punched ear area in comparison to the control group. It has been shown that the healing process is after VEGF and NGF injection driven differentially. In case of VEGF is the cartilage wound repaired by induction of new chondrocytes differentiation. In the case of NGF, the regeneration is supported by immature leukocytes attracted into the punched area. The leukocytes induct angiogenesis so far indirectly by inflammation. The NGF-induced inflammation environment may be a part of mosaic creating the complete picture of regeneration.

Mitochondrial Localized STAT3 Is Involved in NGF Induced Neurite Outgrowth

BackgroundSignal transducer and activator of transcription 3 (STAT3) plays critical roles in neural development and is increasingly recognized as a major mediator of injury response in the nervous system. Cytokines and growth factors are known to phosphorylate STAT3 at tyrosine705 with or without the concomitant phosphorylation at serine727, resulting in the nuclear localization of STAT3 and subsequent transcriptional activation of genes. Recent evidence suggests that STAT3 may control cell function via alternative mechanisms independent of its transcriptional activity. Currently, the involvement of STAT3 mono-phosphorylated at residue serine727 (P-Ser-STAT3) in neurite outgrowth and the underlying mechanism is largely unknown.Principal FindingsIn this study, we investigated the role of nerve growth factor (NGF) induced P-Ser-STAT3 in mediating neurite outgrowth. NGF induced the phosphorylation of residue serine727 but not tyrosine705 of STAT3 in PC12 and primary cortical neuronal cells. In PC12 cells, serine but not tyrosine dominant negative mutant of STAT3 was found to impair NGF induced neurite outgrowth. Unexpectedly, NGF induced P-Ser-STAT3 was localized to the mitochondria but not in the nucleus. Mitochondrial STAT3 was further found to be intimately involved in NGF induced neurite outgrowth and the production of reactive oxygen species (ROS).ConclusionTaken together, the findings herein demonstrated a hitherto unrecognized novel transcription independent mechanism whereby the mitochondria localized P-Ser-STAT3 is involved in NGF induced neurite outgrowth.

The role of nerve growth factor in caspase-dependent apoptosis in human BE(2)C neuroblastoma

Purpose The purpose of the study was to determine if nerve growth factor (NGF) stimulation induces apoptosis in the BE(2)C neuroblastoma cell line in vitro. Methods The LPCX retroviral vector was used to achieve stable transduction of NGF complementary DNA into BE(2)C neuroblastoma cells. Wild-type and NGF-transduced cells were then incubated with varying concentrations of NGF for varying periods. A laddering assay was performed to determine the presence of DNA fragments characteristic of apoptosis. The expression of various cleaved and total caspases was determined by Western immunoblotting. Results p75 receptor expression in the NGF-transduced cell line was equivalent to that in the wild-type cell line, but Trk A receptor expression was significantly decreased in BE(2)C-NGF cells. DNA laddering assay demonstrated that only BE(2)C-NGF cells underwent apoptosis after stimulation with exogenous NGF. BE(2)C-NGF cells have increased expression of cleaved caspase-3 when compared with wild-type cells. Cleaved caspase-3 expression is further increased with exogenous NGF stimulation in the transduced cells. Conclusion This study confirms that NGF stimulation of BE(2)C neuroblastoma cells can induce apoptosis through activation of the caspase cascade in vitro. The differential expression of the receptors Trk A and p75 between the wild-type and NGF-transduced cell lines may explain the differing effects observed.

Neuroprotective role of nerve growth factor in hypoxicischemic injury. From brain to skin.

Hypoxic-ischemic injuries (HII) of the brain, optic pathways, and skin are frequently associated with poor neurological and clinical outcome. Unfortunately, no new therapeutic approaches have been proposed for these conditions. Recently, experimental and clinical studies showed that nerve growth factor (NGF) can improve neurological deficits, visual loss and skin damage after HII. Based on these studies, we report the effects of NGF administration in different lesions of the brain, optic pathways and skin. 2.5S NGF purified and lyophilized from male mouse submaxillary glands was utilized for the treatment. NGF administration was started in absence of recovery after conventional and standardized treatment. One mg NGF was administered via the external catheter into the brain, by drop administration in the eye, and by subcutaneous administration in the skin. We treated 4 patients: 2 children with hypoxic-ischemic brain damage, an adult patient with an optic glioma-induced visual loss and a child with a severe crush syndrome of the lower left limb. After NGF treatment, we observed an amelioration of both neurological and electrophysiological function of the brain, a subjective and objective improvement of visual function, and a gradual improvement of ischemic skin lesion. No side effects were related to NGF treatment in all patients studied. Our observation shows that NGF administration may be an effective and safe adjunct therapy in patients with severe HII. The beneficial and prolonged effect on nerve function suggests a neuroprotective mechanism exerted by NGF on the residual viable neurological pathways of these patients.