Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
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.
 ...
PMID:Expression of NGFI-B mRNA in a rat focal cerebral ischemia-reperfusion model. 903 28

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.
 ...
PMID:Brain derived neurotrophic factor is increased in cerebrospinal fluid of children suffering from asphyxia. 950 26

CD95 (Fas/APO-1) and its ligand (CD95L) belong to a growing cytokine and cytokine receptor family that includes nerve growth factor (NGF) and tumor necrosis factor (TNF) and their corresponding receptors. CD95 expression increases during malignant progression from low-grade to anaplastic astrocytoma and is most prominent in perinecrotic areas of glioblastoma. There is, however, no evidence that CD95 expression in malignant gliomas is triggered by hypoxia or ischemia. Agonistic antibodies to CD95, or the natural ligand, CD95L, induce apoptosis in human malignant glioma cells in vitro. Glioma cell sensitivity to CD95-mediated apoptosis is regulated by CD95 expression at the cell surface and by the levels of intracellular apoptosis-regulatory proteins, including bcl-2 family members. Several cytotoxic drugs synergize with CD95L to kill glioma cells. For as yet unknown reasons, glioma cells may co-express CD95 and CD95L in vitro without undergoing suicide or fratricide. Yet, they kill T cells via CD95/CD95L interactions and are sensitive to exogenously added CD95L. Since CD95L is expressed in gliomas in vivo, too, forced induction of CD95 expression might promote therapeutic apoptosis in these tumors. That glioma cells differ from nontransformed T cells in their sensitivity to CD95 antibodies or recombinant ligand, may allow the development of selective CD95 agonists with high antitumor activity that spare normal brain tissue. A family of death ligand/receptor pairs related to CD95L/CD95, including APO2L (TRAIL) and its multiple receptors is beginning to emerge. Although several issues regarding glioma cell sensitivity to CD95L/CD95-mediated apoptosis await elucidation, CD95 is a promising target for the treatment of malignant glioma.
 ...
PMID:CD95 ligand: lethal weapon against malignant glioma? 954 87

Cerebral ischemia induces damage of cholinergic terminals in the hippocampus, which preceded the delayed neuronal death (DND) of the CA1 pyramidal cells. We investigated the effects of nerve growth factor (NGF) on the cholinergic terminal damage after ischemia. Continuous NGF infusion (0.5 microg/7 days) into the lateral ventricle before and after 5 min ischemia prevented a decrease in choline acetyltransferase (ChAT)-immunoreactivity and disturbance of acetylcholine (ACh) release on the 4th day after ischemia, but not on day 7, i.e., NGF infusion caused delay in the progress of the cholinergic terminal damage. These findings show that the cholinergic terminal damage may result from deficiency of endogenous NGF in an ischemic brain. In addition, we investigated whether NGF would prevent the DND after ischemia. NGF infusion also caused delay in the progress of the DND until day 14. Our results suggested that the neuroprotective effect of NGF on the DND may be secondarily yielded by maintenance of communication between cholinergic terminal and the target CA1 cell, and that prevention of cholinergic terminal damage may be useful for the treatment of cerebrovascular disease.
 ...
PMID:NGF delays rather than prevents the cholinergic terminal damage and delayed neuronal death in the hippocampus after ischemia. 957 62

The neuroprotective potential of the nerve growth factor (NGF) against permanent ischemic brain damage has been investigated in vivo using NGF-transgenic (tg) mice. The expression of the transgene is driven by part of the promoter of the proto-oncogene c-fos, which belongs to the first set of genes activated after brain ischemic insult. Wild-type (wt) mice and tg mice were subjected to permanent focal ischemia induced by electrocoagulation of the middle cerebral artery. Twenty four hours (h) after the ischemic shock, when compared to wt, tg mice displayed a 40% reduction of the infarcted area, which lasted up to 1 week. However, infarcted brain areas were similar in wt and tg mice within the first hours post-occlusion, indicating that NGF acted to block the progression of neuronal damage. Kinetics of NGF synthesis assessed by ELISA was in good agreement with the observed neuroprotective effect, since NGF content peaked 6 h post-ischemia. This was further correlated with the time-course of c-Fos immunoreactivity, detectable only from 6 h post-ischemia. The neuroprotective effect of NGF involved the impairment of apoptotic cell death, as evidenced by a marked decrease of the number of apoptotic profiles inside the ischemic zone in tg mice. These results underline the potential of c-fos-NGF-tg mice to study in vivo the molecular and cellular mechanisms of the NGF-induced neuroprotective effect against ischemic damage.
 ...
PMID:Reduction of cortical infarction and impairment of apoptosis in NGF-transgenic mice subjected to permanent focal ischemia. 964 68

We have previously demonstrated that the neuroprotective effect of the beta2-adrenoceptor agonist clenbuterol in vitro and in vivo was most likely mediated by an increased nerve growth factor (NGF) expression. In the present study, we examined whether clenbuterol was capable of inhibiting apoptosis caused by ischemia. Transient forebrain ischemia was performed in male Wistar rats (300 to 350 g) by clamping both common carotid arteries and reducing the blood pressure to 40 mm Hg for 10 minutes. Clenbuterol (0.1, 0.5, and 1.0 mg/kg intraperitoneally) was administered 3 hours before ischemia or immediately after ischemia. The brains were removed for histologic evaluation 7 days after ischemia. The time course of DNA fragmentation was determined 1, 2, 3 and 4 days after ischemia. Staining with terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end-labeling (TUNEL) was used for further analysis of DNA fragments in situ 3 days after ischemia. The NGF protein was assayed by enzyme-linked immunosorbent assay. Ten-minute forebrain ischemia damaged 80% to 90% of the neurons in the hippocampal CA1 region evaluated 7 days after ischemia. Pretreatment with clenbuterol (0.5 and 1.0 mg/kg) reduced the neuronal damage by 18.1% (P < 0.01) and 13.1% (P < 0.05), respectively. The neuroprotective effect also was found when clenbuterol (0.5 mg/kg) was administered immediately after ischemia (P < 0.05). The DNA laddering appeared in striatum 1 day and in hippocampus 2 days after ischemia and peaked on the third day in both regions. The DNA laddering was nearly abolished in the hippocampus and partially blocked in striatum and cortex by 0.5 mg/kg clenbuterol. These results were confirmed by TUNEL staining. Clenbuterol (0.5 mg/kg intraperitoneally) elevated the NGF protein level by 33% (P < 0.05) in the hippocampus and 41% (P < 0.05) in the cortex 6 hours after ischemia. Three days after ischemia, the NGF levels in these regions were no longer different between the clenbuterol-treated and control groups. This study clearly demonstrates that clenbuterol possesses a neuroprotective activity and a marked capacity to inhibit DNA degradation after global ischemia. The results suggest that clenbuterol increases NGF expression during the first hours after global ischemia and thereby protects neurons against apoptotic damage.
 ...
PMID:Stimulation of beta2-adrenoceptors inhibits apoptosis in rat brain after transient forebrain ischemia. 974 Jan 7

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.
 ...
PMID:High potassium enhances secretion of neurotrophic factors from cultured astrocytes. 979 77

In the present study, embryonic rat neocortex was implanted into the parietal subcortical area of adult naive animals. On the 7th day, the middle cerebral artery was permanently occluded ipsilateral to the graft. Twenty-four hours after middle cerebral artery occlusion, the extent of infarct was visualized by means of 2,3,5-triphenyltetrazolium chloride histochemistry and quantified in four different standardized coronal plains. Subsequently, the effects of fetal tissue grafting and those of transplantation were identified by using glial fibrillary acidic protein and nerve growth factor immunocytochemistry. The grafts integrated well into their new environment and significantly reduced the size of infarct in middle cerebral artery-occluded animals compared with both sham-operated and control rats 24 h postoperation. The underlying mechanism of this phenomenon might be an increased neurotrophic, particularly nerve growth factor, release by the grafted fetal tissue. Moreover, reactive astroglial cells may also trigger the neuroprotection by additional ischemia-induced nerve growth factor release. The present data demonstrate the potential neurotrophin-mediated protective effects of fetal brain tissue implanted into the adult rat brain before unilateral middle cerebral artery occlusion and the beneficial effects of astrocyte activation.
 ...
PMID:Neurotrophin-mediated neuroprotection by solid fetal telencephalic graft in middle cerebral artery occlusion: a preventive approach. 982 Jul 36

The expression of the mRNAs of nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin 3 (NT3) and the neurotrophin receptor, TrkB, was studied in the rat hippocampus by in situ hybridization following normothermic (37 degreesC) and protective hypothermic (33 degreesC) transient cerebral ischemia of 15 min duration. In the resistant dentate gyrus, normothermic ischemia transiently induced NGF mRNA at around 8 h of recovery, while the NT3 mRNA levels were depressed over at least a 24-h recovery period. The levels of BDNF and TrkB were transiently and markedly elevated with a maximal expression at 24 h of recovery. Intraischemic hypothermia reduced the induction of NGF mRNA, while the increase of BDNF mRNA expression occurred earlier during recovery, and the post-ischemic NT3 mRNA depression was not affected. Also, the expression of TrkB mRNA was enhanced, and occurred concomitantly with the elevation of BDNF mRNA. In contrast, there were no changes in neurotrophin and TrkB mRNA in the CA3 and CA1 regions. The expression of BDNF mRNA at 24 h after normothermic ischemia, was attenuated by intraischemic hypothermia. We conclude that, the expressions of NGF, BDNF, NT3 or TrkB mRNA in ischemia-sensitive hippocampal subregions are not increased by protective hypothermia. In contrast, hypothermia induces neurotrophin mRNA alterations in the ischemia-resistant dentate gyrus that may convey protection to sensitive regions.
 ...
PMID:The effect of hypothermia on the expression of neurotrophin mRNA in the hippocampus following transient cerebral ischemia in the rat. 983 92

Docosahexaenoic acid (DHA) accumulates in nerve growth cones (NGC) during perinatal development and it is neuroprotective in ischemia. Because the phospholipases A2 (PLA2) are present in NGC and these enzymes function in both ischemia and long-term potentiation, the relationship between DHA and PLA2 was investigated in the NGC of nerve growth factor-differentiated PC12 cells. When PC12 cells were incubated with [3H]DHA, it primarily esterified in ethanolamine glycerolipids and concentrated initially in cell bodies with similar levels present in the neurite/nerve growth cone (N/NGC) fraction after 4 days. PLA2 activity in the N/NGC fraction was investigated using [14C]arachidonic acid-labeled phosphatidylinositol ([14C-AA]PI) as substrate. Heat denaturation and pharmacological inhibition showed that much of the PLA2 activity was calcium-independent and secretory rather than cytosolic. Supplementing the media with as little as 33 nM DHA significantly reduced PLA2 activity in the N/NGC fraction.
 ...
PMID:Docosahexaenoic acid decreases phospholipase A2 activity in the neurites/nerve growth cones of PC12 cells. 985 64


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>