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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Very recently, contradictory results were presented as to the effects of exogenous nerve growth factor (NGF) on the hippocampal delayed neuronal necrosis following transient ischemia. In the present study, we administered a large amount of NGF with the atelocollagen mini-pellet system, measured the local NGF contents, and evaluated the effect of this neurotrophic factor on the postischemic hippocampal pyramidal cells in gerbils. We concluded that the exogenous NGF, when given continuously at sufficient concentrations, prevents pyramidal cell damage. The possible cause of discrepancy in previous studies is discussed.
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PMID:Protective effect of NGF atelocollagen mini-pellet on the hippocampal delayed neuronal death in gerbils. 143 29

The expression profile of neurotrophin-3 (NT-3) mRNA in the rat hippocampus after forebrain ischemia was investigated by Northern blot and S1 nuclease protection analyses. The NT-3 transcripts in the hippocampus immediately decreased after ischemic insult, became undetectable within 3 h and remained at undetectable levels for at least 7 days. In contrast, the expression of c-fos and c-jun mRNA transiently increased both in the cerebral cortex and in the hippocampus. These results suggest that brain ischemia triggers dynamic changes in gene expression including a neurotrophic factor, which may cause functional and/or morphological changes of the neuronal network.
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PMID:Decreased expression of neurotrophin-3 mRNA in the rat hippocampus following transient forebrain ischemia. 161 77

Transforming growth factors beta are multifunctional proteins and regulators of cell proliferation and differentiation. Transforming growth factor-beta s have the capacity to rescue adult neurons from ischemia- and glutamate-induced cell death and are prominent in the embryonic and adult brain including striatum and substantia nigra. In the present study we show that transforming growth factors-beta 1, -2, and -3 promote, in a dose-dependent fashion, in vitro survival of tyrosine hydroxylase-immunoreactive dopaminergic neurons isolated from the embryonic rat mesencephalon floor. The magnitude of the effect, which was half-maximal at a concentration of 20 pM, was identical for all three transforming growth factor-isoforms and matched that of fibroblast growth factor-2. Unlike fibroblast growth factor-2, however, transforming growth factor-beta s did not increase numbers of astroglial cells visualized by using antibodies to glial fibrillary acidic protein, and had no effect on cell proliferation monitored by incorporation of BrdUrd. Transforming growth factor-beta s were significantly more potent than fibroblast growth factor-2 in protecting dopaminergic neurons against N-methyl-4-phenylpyridinium ion toxicity. RT-PCR analysis indicated that the effect of transforming growth factor-beta s is not mediated by glial cell-derived neurotrophic factor, which was not detectable in cultures at various time points. On the other hand transforming growth factor-beta 2 mRNA could be detected in freshly isolated and cultured mesencephalic cells, and its immunoreactivity has also been demonstrated in the embryonic day 14 mesencephalon floor. We conclude that transforming growth factor-beta has trophic and protective effects on developing dopaminergic neurons.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Transforming growth factor-beta promotes survival of midbrain dopaminergic neurons and protects them against N-methyl-4-phenylpyridinium ion toxicity. 770 May 16

The identification of neurotrophic factors ameliorating secondary neuronal death in the mammalian CNS has raised hopes for improved treatment strategies in neurodegenerative diseases, CNS trauma and ischemia. Glial cell-line derived neurotrophic factor (GDNF) has potent neuroprotective properties in both the CNS and PNS. We sought to investigate whether GDNF exerts survival promoting effects on axotomized retinal ganglion cells (RGCs) in the adult rat in vivo. Transection of the optic nerve induces delayed retrograde death of approximately 85% of RGCs within 14 days. Intraocular GDNF rescued 21% of the RGCs which would otherwise have died after axotomy (34% of the normal control population), thereby extending the group of neuronal populations responsive to GDNF.
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PMID:In vivo neurotrophic effects of GDNF on axotomized retinal ganglion cells. 942 3

Brain derived neurotrophic factor (BDNF) is a neurotrophic factor that is relatively highly expressed in developing and adult brain. Whereas clinical determinations of nerve growth factor (NGF) in human serum and cerebrospinal fluid (CSF) in different conditions have been undertaken there are no reports on levels of BDNF in human CSF. Here we show that BDNF is increased in CSF of neonatal children suffering from asphyxia which is characterised by periods of brain hypoxic-ischemia. In contrast to BDNF, levels of CSF NGF were largely decreased in these children. The present results show that BDNF can be detected in human CSF and that the levels increase following hypoxic-ischemic brain injury. As suggested by animal studies the increased BDNF might counteract neuronal damage observed in these patients following asphyxia.
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PMID:Brain derived neurotrophic factor is increased in cerebrospinal fluid of children suffering from asphyxia. 950 26

Hepatocyte growth factor (HGF), a natural ligand for the c-met protooncogene product, exhibits mitogenic, motogenic, and morphogenic activities for regeneration of the liver, kidney, and lung. Recently, HGF was clearly shown to enhance neurite outgrowth in vitro. To determine whether HGF has a neuroprotective action against the death of neurons in vivo, we studied the effect of HGF on delayed neuronal death in the hippocampus after 5-minute transient forebrain ischemia in Mongolian gerbils. Continuous postischemic intrastriatal administration of human recombinant HGF (10 or 30 micrograms) for 7 days potently prevented the delayed death of hippocampal neurons under both anesthetized and awake conditions. Even when HGF infusion started 6 hours after ischemia (i.e., in a delayed manner), HGF exhibited a neuroprotective action. We conclude that HGF, a novel neurotrophic factor, has a profound neuroprotective effect against postischemic delayed neuronal death in the hippocampus, which may have implications for the development of new therapeutic strategies for ischemic neuronal damage in humans.
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PMID:Protection of hippocampal neurons from ischemia-induced delayed neuronal death by hepatocyte growth factor: a novel neurotrophic factor. 953 98

Hepatocyte growth factor (HGF) is a potent pleiotrophic peptide which has a trophic role for neuronal cells. As it exerts its effect only after a conversion to its heterodimeric active form, the activation step, which is catalyzed by an enzyme serine protease named HGF activator (HGFA), is of great importance. HGF activated by HGFA may act as a protecting agent in injured brain. In the present study, we investigated expression of immunoreactive HGF and HGFA in rat brain after permanent middle cerebral artery (MCA) occlusion. By immunohistochemical analysis, HGF and HGFA were normally expressed only in ependymal cells and choroid plexus. At 1 h after MCA occlusion, neurons in the ischemic penumbra region of the cerebral cortex slightly expressed immunoreactive HGFA. HGF was not induced at that time. At 3 h of ischemia, however, immunoreactive HGF as well as HGFA became detectable in neurons of the ischemic cerebral cortex and caudate. Immunoreactivity for HGF continued to increase until 24 h, while that for HGFA remained almost constant from 3 to 24 h. No glial or vascular endothelial cells expressed HGF nor HGFA. By Western blot analysis for HGF, a single band of molecular weight (MW) 34 kDa became apparent at 24 h, corresponding to the light chain of the active form HGF. The present study suggests that HGF and HGFA were induced in neurons under permanent ischemia with slightly different temporal profiles. Through activation by HGFA, the active form of HGF could serve as a neurotrophic factor in ischemic brain.
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PMID:Inductions of hepatocyte growth factor and its activator in rat brain with permanent middle cerebral artery occlusion. 967 23

Elevation of extracellular potassium concentration ([K+]o) in the central nervous system (CNS), which is observed such after physiological stimuli and during ischemia, is known to be regulated by astrocytes. We suspected that in response to increased [K+]o, astrocytes might secrete some neurotrophic factor(s) to promote the survival of active and/or ischemically damaged neurons. In the present study, we examined neurotrophic activity contained in HK-ACM, i.e., astrocyte-conditioned medium (ACM) obtained after culturing astrocytes in 40 mM potassium-containing medium (HK medium). Addition of HK-ACM to basal forebrain cultures from postnatal 2-week-old (P2w) rats increased both the choline acetyltransferase (ChAT) activity (4.40-fold) and the number of ChAT-positive neurons (2.01-fold) as compared with non-conditioned HK medium. On the other hand, the neurotrophic effects of LK-ACM, i.e., ACM collected after culturing astrocytes in 4 mM potassium-containing medium (LK medium), were much weaker (2.85- and 1.41-fold for ChAT activity and number of ChAT-positive neurons, respectively) than those of HK-ACM. The neurotrophic effects of ACMs increased in a manner dependent on potassium concentration and on astrocyte culture time. Addition of an antibody against nerve growth factor (NGF) neutralized the neurotrophic effects of HK- and LK-ACMs. Direct quantification of NGF protein in ACMs by the two-site ELISA method demonstrated that a high concentration of potassium enhanced NGF secretion from cultured astrocytes. These results suggested that astrocytes secrete NGF in response to [K+]o elevation in the CNS.
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PMID:High potassium enhances secretion of neurotrophic factors from cultured astrocytes. 979 77

Consumption of alcohol during pregnancy can result in central nervous system deficits in infants ranging from fetal alcohol effects to fetal alcohol syndrome. Changes in cerebral metabolism causing ischemic in utero conditions can also result from ethanol (EtOH). Growth factors have been shown to ameliorate ischemic damage and EtOH-induced neurotoxicity. However, using an in vitro model system of fetal alcohol effects/fetal alcohol syndrome, this study examines the neuroprotective effects of nerve growth factor, brain-derived neurotrophic factor, or glial cell line derived neurotrophic factor against EtOH treatment (0, 200, 400, 800, or 1, 600 mg/dl) combined with acute ischemia (2-hour hypoxia in EtOH-containing glucose-free media) followed by chronic hypoglycemia (16-hour glucose deprivation in EtOH-containing media). 3-(4, 5-Dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assays assessed relative neurotoxicity. Glial cell derived neurotrophic factor was not neuroprotective. Nerve growth factor protected against ischemia/hypoglycemia combined with 0-1,600 mg/dl EtOH. Brain-derived neurotrophic factor protected against ischemia/hypoglycemia combined with 0-800 mg/dl EtOH. These studies demonstrate marked growth factor neuroprotection against a myriad of conditions encountered by developing EtOH-exposed fetuses.
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PMID:BDNF and NGF afford in vitro neuroprotection against ethanol combined with acute ischemia and chronic hypoglycemia. 1007 4

This review primarily discusses work that has been performed in our laboratories and that of our direct collaborators and therefore does not represent an exhaustive review of the current literature. Our aim is to further discuss the role that gene expression plays in neuronal plasticity and pathology. In the first part of this review we examine activity-dependent changes in the expression of inducible transcription factors (ITFs) and neurotrophins with long-term potentiation (LTP) and kindling. This work has identified particular ITFs (Krox-20 and Krox-24) and neurotrophin systems (particularly the brain-derived neurotrophic factor (BDNF)/tyrosine receptor kinase-B, Trk-B system) that may be involved in stabilizing long-lasting LTP (i.e. LTP3). We also show that changes in the expression of other ITFs (Fos, Jun-D and Krox-20) and the BDNF/trkB neurotrophin system may play a central role in the development of hippocampal kindling, an animal model of human temporal lobe epilepsy. In the next part of this review we examine changes in gene expression after neuronal injuries (ischemia, prolonged seizure activity and focal brain injury) and after nerve transection (axotomy). We identify apoptosis-related genes (p53, c-Jun, Bax) whose delayed expression selectively increases in degenerating neurons, further suggesting that some forms of neuronal death may involve apoptosis. Moreover, since overexpression of the tumour-suppressor gene p53 induces apoptosis in a wide variety of dividing cell types we speculate that it may perform the same function in post-mitotic neurons following brain injuries. Additionally, we show that neuronal injury is associated with rapid, transient, activity-dependent expression of neurotrophins (BDNF and activinA) in neurons, contrasting with a delayed and more persistent injury-induced expression of certain growth factors (IGF-1 and TGFbeta) in glia. In this section we also describe results linking ITFs and neurotrophic factor expression. Firstly, we show that while BDNF and trkB are induced as immediate-early genes following injury, the injury-induced expression of activinA and trkC may be regulated by ITFs. We also discuss whether loss of retrograde transport of neurotrophic factors such as nerve growth factor following nerve transection triggers the selective and prolonged expression of c-Jun in axotomized neurons and whether c-Jun is responsible for regeneration or degeneration of these axotomized neurons. In the last section we further examine the role that gene expression may play in memory formation, epileptogenesis and neuronal degeneration, lastly speculating whether the expression of various growth factors after brain injury represents an endogenous neuroprotective response of the brain to injury. Here we discuss our results which show that pharmacological enhancement of this response with exogenous application of IGF-1 or TGF-beta reduces neuronal loss after brain injury.
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PMID:Activity and injury-dependent expression of inducible transcription factors, growth factors and apoptosis-related genes within the central nervous system. 1008 Mar 84


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