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

Cerebral ischemia is known to induce the expression of several immediate early genes (IEGs), including c-fos and c-jun, which subsequently regulate a number of late effector genes. In this study, we examined the expression of NGFI-B (or nur 77) mRNA in a rat focal cerebral ischemia-reperfusion model. NGFI-B is a member of the IEGs which encodes for a nuclear receptor and is rapidly induced by nerve growth factor (NGF). Northern blot analysis showed a rapid but transient enhancement of NGFI-B mRNA, a peak level for which was observed at 30 min of reperfusion following 60 min ischemic insult. At the peak level, quantitative analysis of the blot indicated a 12-fold and 4-fold increase of NGFI-B mRNA in the ischemic cortex and ipsilateral hippocampus, respectively, as compared to the sham-operated control. No apparent changes in mRNA levels were observed within contralateral sites of the cortex. Results from in situ hybridization showed that severe ischemia (60 min) resulted in a marked increase of NGFI-B mRNA throughout the entire ischemic cerebral cortex. The increase was particularly notable in the frontal, occipital, perirhinal and piriform cortical regions and in the dentate gyrus and CAI-3 regions of the ipsilateral hippocampus. A marked induction was also noted in the ipsilateral caudate putamen. Unlike the induction profile of NGFI-B mRNA, severe ischemia resulted in bilateral increases of its family gene, NGFI-A mRNA. The spatial induction profile is similar to that of NGFI-B mRNA in both hemispheres, except within the region of the contralateral dentate gyrus which showed low levels of NGFI-A mRNA. The expression pattern of NGF and BDNF mRNA, upstream genes of NGFI-B, were also examined. Interestingly the temporal and spatial expression patterns of BDNF mRNA were very similar to that of NGFI-A mRNA under the same conditions, whereas increased NGF and NGFI-B mRNA were observed only in the ipsilateral hemisphere. It is likely that multiple and/or overlapping pathways are activated subsequent to ischemic challenge which in turn are crucial for cel survival and/or functional recovery following focal cerebral ischemia.
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PMID:Expression of NGFI-B mRNA in a rat focal cerebral ischemia-reperfusion model. 903 28

Hypoxic-ischemic brain injury in survivors of perinatal asphyxia is a frequently encountered clinical problem for which there is currently no effective therapy. Neurotrophins, such as brain-derived neurotrophic factor (BDNF), can protect responsive neurons against cell death in some injury paradigms. While the role of BDNF in hypoxic-ischemic brain injury is not clear, evidence suggests that BDNF may have different effects in the developing, as opposed to the adult, brain. We found that a single intracerebroventricular (ICV) injection of BDNF resulted in rapid and robust phosphorylation of trk receptors in multiple brain regions in the postnatal day (PD) 7 rat brain. BDNF also markedly protected against hypoxic-ischemic brain injury at PD7. It protected against 90% of tissue loss due to hypoxic-ischemia when given just prior to the insult and against 50% of tissue loss when give after the insult. In contrast, ICV injection of BDNF in PD21 and adult rats resulted in little trk phosphorylation and less dramatic protection against unilateral hypoxic-ischemic injury at PD21. Because of its potent neuroprotective actions in the developing brain, BDNF may be a potential treatment for asphyxia and other forms of acute injury in the perinatal period.
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PMID:Marked age-dependent neuroprotection by brain-derived neurotrophic factor against neonatal hypoxic-ischemic brain injury. 912 10

Preischemic hyperglycemia or superimposed hypercapnia exaggerates brain damage caused by transient forebrain ischemia. Because high regional levels of brain-derived neurotrophic factor (BDNF) protein correlate with resistance to ischemic damage, we studied the expression of BDNF mRNA using in situ hybridization in rats subjected to 10 minutes of forebrain ischemia under normoglycemic, hyperglycemic, or hypercapnic conditions. Compared with normoglycemic animals, the increase of BDNF mRNA using in situ hybridization in rats subjected to 10 minutes of forebrain ischemia under normoglycemic, or hypercapnic conditions. Compared with normoglycemic animals, the increase of BDNF mRNA in dentate granule cells was attenuated and that in CA3 pyramidal neurons completely prevented in hyperglycemic rats. No ischemia-induced increases of BDNF mRNA levels in the hippocampal formation were detected in hypercapnic animals. Hyperglycemic and hypercapnic rats showed transiently decreased expression of BDNF mRNA levels in the cingulate cortex, which was not observed in normoglycemic animals. The results suggest that suppression of the BDNF gene might contribute to the increased vulnerability of the CA3 region and cingulate cortex in hyperglycemic and hypercapnic animals.
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PMID:Hyperglycemia and hypercapnia suppress BDNF gene expression in vulnerable regions after transient forebrain ischemia in the rat. 939 29

1. At least two different groups of molecules can be considered neurotrophic factors because they exert a variety of effects upon neural cells. The first consists of the numerous families of polypeptide growth factors known to take part in almost all stages of neural cell growth and functioning, including development, differentiation, survival and pathology. The second group also is characterized by extensive complexity of multiple forms, and consists of the sialic acid-containing glycosphingolipids or gangliosides. These molecules also take part in the transfer of information from the extracellular milieu to the cell interior, and, similarly to growth factors, are participants in such aspects as development, differentiation and functioning. 2. In this short overview, we consider the existing data on the neuroprotective effects of growth factors [e.g., basic fibroblast growth factor (bFGF), epidermal growth factor (EGF) and brain-derived neurotrophic factor] and one species of ganglioside (GM1) against retinal ischemia in vivo and cerebral excitotoxicity in vitro. 3. We used three different experimental models to investigate their relevance to ischemic and excitotoxic conditions in the retina and have shown that: (a) both bFGF and EGF show highly effective neuroprotection for rat retinal neurons exposed to toxic levels of glutamate or its nonphysiological agonist kainate in vitro (b) retinal glial cells suffer morphological perturbations after glutamate or kainate treatment, and this effect depends on neuron-glial interactions; (c) these glial changes can also be corrected by posttreatment with either bFGF or EGF in vitro; (d) with the use of an in vivo animal model involving anterior chamber pressure-induced ischemia in adult rats, either pretreatment by intraperitoneal injection of GM1 or posttreatment by intraocular injection of the same ganglioside significantly reduces histological damage to inner nuclear regions. 4. Hence both groups of trophic molecules show interesting features for retinal ischemic treatment.
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PMID:Growth factors and gangliosides as neuroprotective agents in excitotoxicity and ischemia. 951 73

Nerve growth factor, brain-derived neurotrophic factor, and other neurotrophic factors have been reported to have neuroprotective effects against global ischemia. To investigate whether the homodimer of platelet-derived growth factor B-chain (PDGF-BB) can protect neurons against focal temporary ischemia, PDGF-BB was administered to the rat brain for a prolonged period prior to, during, and after ischemia, since PDGF-BB protected rat neurons from global ischemia in our previous study. A total of 82 male Sprague-Dawley rats were used. Recombinant PDGF-BB, or saline was administered into the left neocortex via an implanted osmotic pump for 3 days (1.2 microg in total), 7 days (2 microgram or 4 microgram in total), or 14 days (4 microgram in total) pre-ischemia and 2 days post-ischemia. In an additional group, PDGF-BB (4 microgram in total) was administered for 14 days by osmotic pump and focal ischemia was induced after an additional 7-day interval following removal of the pump. Focal temporary ischemia was induced in the left MCA territory by bilateral CCA and MCA occlusion for 2 h. All rats were sacrificed 2 days after ischemia and the volume of cerebral infarct was analyzed using TTC staining. In a separate set of animals, regional cerebral blood flow (rCBF) was monitored by the hydrogen clearance method and laser Doppler flowmetry (LDF) of the neocortex after 14 days of intracerebral administration of PDGF-BB or saline. In the group receiving PDGF-BB (4 microgram in total) for 7 or 14 days pre-ischemia, there was a significant reduction of neocortical infarction compared to that in the control or saline-infused group. The size of cerebral infarct was smallest in the group that received PDGF-BB for 14 days, when ischemia was induced 7 days after removal of the pump. Regarding rCBF measurement, there were no significant differences in groups receiving PDGF-BB or saline infusion for 14 days. The potent neuroprotective effect of PDGF-BB on global ischemia was also demonstrated in the focal ischemia model. However, prolonged intracerebral infusion for 7 to 14 days was necessary to achieve a significant reduction of infarct volume. Neuroprotection was not due to increased collateral flow during ischemia.
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PMID:Induction of infarct tolerance by platelet-derived growth factor against reversible focal ischemia. 951 39

Extracellular stimuli such as neurotransmitters, neurotrophins, and growth factors in the brain regulate critical cellular events, including synaptic transmission, neuronal plasticity, morphological differentiation and survival. Although many such stimuli trigger Ser/Thr-kinase and tyrosine-kinase cascades, the extracellular signal-regulated kinases, ERK1 and ERK2, prototypic members of the mitogen-activated protein (MAP) kinase family, are most attractive candidates among protein kinases that mediate morphological differentiation and promote survival in neurons. ERK1 and ERK2 are abundant in the central nervous system (CNS) and are activated during various physiological and pathological events such as brain ischemia and epilepsy. In cultured hippocampal neurons, simulation of glutamate receptors can activate ERK signaling, for which elevation of intracellular Ca2+ is required. In addition, brain-derived neurotrophic factor and growth factors also induce the ERK signaling and here, receptor-coupled tyrosine kinase activation has an association. We describe herein intracellular cascades of ERK signaling through neurotransmitters and neurotrophic factors. Putative functional implications of ERK and other MAP-kinase family members in the central nervous system are give attention.
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PMID:Role of MAP kinase in neurons. 955 3

The neurotrophins NGF, BDNF, NT-3 and NT-4 have a wide range of effects in the development and regeneration of neural circuits in the visual system of vertebrates. This review focuses on the localization and functions of neurotrophins in the retina, lateral geniculate nucleus, suprachiasmatic nucleus, superior colliculus/optic tectum, and isthmic nuclei. Research of the past 20 years has shown that neurotrophins and their receptors are localized in numerous visual centers from the retina to the visual cortex, and that neurotrophins influence proliferation, neurite outgrowth and survival of cells in the visual system in vitro and in vivo. A relationship between electrical activity and neurotrophic functions has been established in several visual centers in the CNS, and neurotrophins have been implicated in synaptic plasticity in the visual cortex. Besides functions of neurotrophins as retrograde, target-derived trophic factors, recent data indicate that neurotrophins may have anterograde, afferent as well as local, paracrine actions in the retina, optic nerve and the visual cortex. Some neurotrophins appear to regulate proliferation and survival of glial cells in the optic pathways. Neurotrophins increase the survival of retinal ganglion cells after axotomy or ischemia and they promote the regeneration of retinal ganglion cell axons in some vertebration. Neurotrophins also rescue photoreceptors from degeneration. These findings implicate the neurotrophins not only as important regulators during development, but also as potential therapeutic agents in degenerative retinal diseases and after optic nerve injury.
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PMID:Neurotrophins in the developing and regenerating visual system. 958 2

Delayed cell death involving the CA1 area of the hippocampus was produced following 5 minutes of transient forebrain ischemia in gerbils. Cell death mainly affected CA1 pyramidal neurons, whereas parvalbumin-immunoreactive (parv-ir) cells were spared. Synaptophysin immunoreactivity was observed in the strata oriens and radiatum of CA1 for months, although immunoreactivity decreased in gerbils surviving 1 year post-ischemia. Golgi studies disclosed a few pyramidal neurons with dendrites, variably covered with dendritic spines, in the CA1 area of 1-year surviving gerbils. In the normal gerbil, the majority of CA1 neurons expressed brain-derived neurotrophic factor (BDNF), tyrosine protein kinase C (TrkC), fibroblast growth factor receptor 1 (Flg), transforming growth factor-alpha (TGF-alpha), and epidermal growth factor-receptor (EGF-R), but only a minority of cells were tyrosine protein kinase B (TrkB)-immunoreactive. Marked reduction in the number of BDNF-, TrkC-, Flg-, TGF-alpha-, and EGF-R-ir cells was observed in CA1 from 24 hours to 1 year after ischemia. In contrast, TrkB-ir cells survived the ischemic insult. Double-labeling immunohistochemistry disclosed that about 90% of surviving BDNF-ir and 85% of TrkB-ir neurons co-localized parvalbumin in the CA1 area. In control gerbils, only about 5% of BDNF-ir cells in CA1 co-expressed TrkB. However, TrkB co-localized in about 95% of surviving BDNF-ir neurons in CA1 in ischemic gerbils. In addition, parvalbumin was co-expressed in about 90% of TrkC-, 95% Flg-, and 85% EGF-R-ir surviving neurons in the stratum pyramidale of CA1. Finally, basic fibroblast growth factor (bFGF) was expressed by reactive astrocytes from day 4 onwards. These data show that the subpopulation of TrkB-/parv-ir neurons in CA1 survive the ischemic episode and that multiple neurotrophic signals converge in surviving neurons of the gerbil hippocampus following transient forebrain ischemia.
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PMID:Multiple neurotrophic signals converge in surviving CA1 neurons of the gerbil hippocampus following transient forebrain ischemia. 959 May 52

Utilizing a specific polyclonal antibody against a peptide unique for brain-derived neurotrophic factor (BDNF), we investigated the regional and temporal profiles of immunoreactivity of the BDNF protein in the rat hippocampus after transient forebrain ischemia. The pattern of immunoreactivity for the BDNF receptor (TrkB) was also examined and compared with that for BDNF. In the early phase after ischemia, we observed a distinct regional difference in immunoreactivity between the pyramidal cell layer and the stratum radiatum of the CA1 subfield. In the pyramidal cell layer, there was a rapid and transient increase in the positive immunostaining for both BDNF and TrkB. By contrast, in the stratum radiatum there was a marked decrease in BDNF immunoreactivity, but not one in that of TrkB. One week after ischemia, high immunoreactivity for both BDNF and TrkB was observed in the reactive astrocytes in the dendritic field of the CA1 subfield. These findings suggest that a transport of BDNF from the neuronal soma to the dendrites of the stratum radiatum might be ceased after the ischemic insult. Thus, a dysfunctional autocrine mechanism of BDNF within the CA1 neuron may be involved in the pathogenesis of selective neuronal damage after ischemia.
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PMID:Reduction in brain-derived neurotrophic factor protein level in the hippocampal CA1 dendritic field precedes the delayed neuronal damage in the rat brain. 969 60

Evidence has accumulated to suggest that the NMDA glutamate receptor subtype plays an important role in neuronal degeneration evoked by hypoxia, ischemia, or trauma. Cerebellar granule cells in culture are vulnerable to NMDA-induced neuronal excitotoxicity. In these cells, brain-derived neurotrophic factor (BDNF) and basic fibroblast growth factor (FGF2) prevent the excitotoxic effect of NMDA. However, little is known about the molecular mechanisms underlying the protective properties of these trophic factors. Using cultured rat cerebellar granule cells, we investigated whether BDNF and FGF2 prevent NMDA toxicity by downregulating NMDA receptor function. Western blot and RNase protection analyses were used to determine the expression of the various NMDA receptor subunits (NR1, NR2A, NR2B, and NR2C) after BDNF or FGF2 treatment. FGF2 and BDNF elicited a time-dependent decrease in the expression of NR2A and NR2C subunits. Because NMDA receptor activation leads to increased intracellular Ca2+ concentration ([Ca2+]i), we studied the effect of the BDNF- and FGF2-induced reduction in NR2A and NR2C synthesis on the NMDA-evoked Ca2+ responses by single-cell fura-2 fluorescence ratio imaging. BDNF and FGF2 reduced the NMDA-mediated [Ca2+]i increase with a time dependency that correlates with their ability to decrease NR2A and NR2C subunit expression, suggesting that these trophic factors also induce a functional downregulation of the NMDA receptor. Because sustained [Ca2+]i is believed to be causally related to neuronal injury, we suggest that BDNF and FGF2 may protect cerebellar granule cells against excitotoxicity by altering the NMDA receptor-Ca2+ signaling via a downregulation of NMDA receptor subunit expression.
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PMID:Brain-derived neurotrophic factor and basic fibroblast growth factor downregulate NMDA receptor function in cerebellar granule cells. 974 62


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