Transient changes of brain-derived neurotrophic factor (BDNF) mRNA expression in hippocampus during moderate ischemia induced by chronic bilateral common carotid artery occlusions in the rat (original) (raw)
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Molecular Brain Research, 1996
Levels of BDNF mRNA and protein were measured in the rat brain using in situ hybridization and a two-site enzyme immunoassay. Under basal conditions, the highest BDNF concentration was found in the dentate gyrus (88 ng/g), while the levels in CA3 (50 ng/g), CA1 (18 ng/g) and parietal cortex (8 ng/g) were markedly lower. Following 10 min of forebrain ischemia, BDNF protein increased transiently in the dentate gyrus (to 124% of control at 6 h after the insult) and CA3 region (to 131% of control, at 1 week after the insult). In CA1 and parietal cortex, BDNF protein decreased to 73-75% of control at 24 h. In contrast, BDNF mRNA expression in dentate granule cells and CA3 pyramidal layer was transiently elevated to 287 and 293% of control, respectively, at 2 h, whereas no change was detected in CA1 or neocortex. The regional BDNF protein levels shown here correlate at least partly with regional differences in cellular resistance to ischemic damage, which is consistent with the hypothesis of a neuroprotective role of BDNF.
Brain-derived neurotrophic factor blood levels in two models of transient brain ischemia in rats
General physiology and biophysics, 2013
We monitored possible influence of transient focal and global brain ischemia on BDNF blood level. In both models noticeable fluctuation of BDNF concentration mainly in reperfusion was observed. During the first 90 min, BDNF in total blood and in blood cells continuously decreased in both models but plasma BDNF raised at 40 min and peaked at 90 min of reperfusion. Our data confirm the impact of transient brain ischemia on BDNF levels in the circulatory system, suggest blood cells as a possible source of BDNF and demonstrate the interdependence of blood compartments and physiological state of an affected organism.
AbstractöGene expression for glial cell line-derived neurotrophic factor (GDNF) family ligands and receptors was analyzed with in situ hybridization after two focal ischemic insults of di¡erent severities. Focal ischemia was induced in rats by either 30 min or 2 h of middle cerebral artery occlusion (MCAO), causing damage to the striatum only, or involving also the parietal cortex, respectively. We found modest, transient elevation of GDNF mRNA in the dentate granule cell layer. In addition, the number of GDNF mRNA-expressing cells increased in the cortex and striatum after 2 h or 30 min of MCAO, respectively. No changes of neurturin or persephin mRNA expression were detected. Both c-Ret and GFRK1 mRNA levels were markedly increased in the ipsilateral cortex outside the ischemic lesion at 6^24 h after the 2-h insult, whereas GFRK2 expression was decreased in cortical areas both within and outside the lesion. Similar increases of c-Ret and GFRK1 mRNA levels were detected in the striatum, and to a lesser extent, in the cortex following 30 min of MCAO. The 2-h insult also gave rise to transient increases of c-Ret and GFRK1 mRNA in hippocampal subregions. Thirty minutes and 2 h of MCAO lead to elevated c-Ret, and GFRK1 or GFRK2 mRNA expression, respectively, in the ipsilateral ventroposterolateral thalamic nucleus. Both insults induced increased levels of GFRK1 mRNA in the subventricular zone of the lateral ventricle.
Protective Effects of Glial Cell Line-Derived Neurotrophic Factor in Ischemic Brain Injury
Annals of The New York Academy of Sciences, 2002
A BSTRACT : Glial cell line-derived neurotrophic factor (GDNF), a member of the transforming growth factor- (TGF- ) superfamily, has been shown to have trophic activity on dopaminergic neurons. Recent studies indicate that GDNF can protect the cerebral hemispheres from damage induced by middle cerebral arterial ligation. We found that such neuroprotective effects are mediated through specific GDNF receptor alpha-1 (GFR ␣ 1). Animals with a deficiency in GFR ␣ -1 have less GDNF-induced neuroprotection. Ischemia also enhances nitric oxide synthase (NOS) activity, which can be attenuated by GDNF. These.data suggest that GDNF can protect against ischemic injury through a GFR ␣ -1/NOS mechanism. We also found that the receptor for GDNF, GFR ␣ 1, and its signaling moiety c-Ret were upregulated, starting immediately after ischemia. This upregulation suggests that activation of an endogenous neuroprotective mechanism occurs so that responsiveness of GDNF can be enhanced at very early stages during ischemia.
Journal of Cerebral Blood Flow & Metabolism, 1999
To examine a possible protective effect of exog enous glial cell line-derived neurotrophic factor (GDNF) gene expression against ischemic brain injury, a replication defective adenoviral vector containing GDNF gene (Ad GDNF) was directly injected into the cerebral cortex at I day before 90 minutes of transient middle cerebral artery occlusion (MCAO) i\l rats. 2,3,5-Triphenyltetrazolium chloride staining showed that infarct volume of the Ad-GDNF-injected group at 24 hours after the transient MCAO was significantly smaller than that of vehicle-or Ad-LacZ-treated group. Enzyme-linked immunosorbent assay (ELISA) for immunoreactive GDNF demonstrated that GDNF gene products in the Ad-GDNF injected group were higher than those of vehicle-treated group at 24 hours after transient MCAO. Immunoreactive GDNF Glial cell line-derived neurotrophic factor (GDNF) has a potent neuroprotective effect on a variety of neuronal damage in vitro or in vivo (Lin et aI., 1993; Henderson et aI., 1994; Beck et aI., 1995; Li et aI., 1995; Tomac et aI., 1995). Our previous papers and another report have also demonstrated the amelioration of ischemic brain injury by GDNF application after middle cerebral artery occlu-
Journal of Cerebral Blood Flow & Metabolism, 2013
The ‘new penumbra’ concept imbues the transition between injury and repair at the neurovascular unit with profound implications for selecting the appropriate type and timing of neuroprotective interventions. In this conceptual study, we investigated the protective effects of pigment epithelium-derived factor (PEDF) and compared them with the properties of epidermal growth factor (EGF) in a rat model of ischemia–reperfusion injury. We initiated a delayed intervention 3 hours after reperfusion using equimolar amounts of PEDF and EGF. These agents were then administered intravenously for 4 hours following reperfusion after 1 hour of focal ischemia. Magnetic resonance imaging indices were characterized, and imaging was performed at multiple time points post reperfusion. PEDF and EGF reduced lesion volumes at all time points as observed on T2-weighted images (T2-LVs). In addition PEDF selectively attenuated lesion volume expansion at 48 hours after reperfusion and persistently modulated ...
Tissue levels of brain-derived neurotrophic factor (BDNF) protein were studied using enzyme immunoassay in different forebrain regions in the ipsi-and contralateral hemispheres of rats housed under enriched or standard conditions after the middle cerebral artery ligation. BDNF levels in the ipsilateral to ligation side was signi®cantly higher only in the frontal cortex of standard as compared to enriched rats. However, BDNF overall was more abundant in standard than in enriched group. In addition, BDNF levels detected in the hippocampus and frontal cortex on the ischemic side of standard rats was higher as compared to contralateral side. The present study shows that housing conditions after permanent middle cerebral artery ligation leads to differential regulation of BDNF protein levels in forebrain regions which might have important implication for post-ischemic recovery. q