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

Glial cell line-derived neurotrophic factor, a member of the transforming growth factor-beta superfamily, is a potent neurotrophic factor, which has a variety of biological activities that affect several types of neurons in both the central and peripheral nervous systems. In this study, we examined the effects of glial cell line-derived neurotrophic factor on delayed neuronal death in the hippocampal CA1 region of rats after transient forebrain ischemia. In the control rats pretreated with the vehicle, transient forebrain ischemia-induced delayed neuronal death in the hippocampal CA1 region was observed seven days after reperfusion. Pretreatment with glial cell line-derived neurotrophic factor (1.0 microg), which was directly microinjected into the right hippocampal CA1 region, gave significant protection against the delayed hippocampal neuronal death. On the contralateral side of the hippocampus, which was not injected with glial cell line-derived neurotrophic factor, delayed neuronal death similar to that seen in vehicle-treated control animals was observed. Intracerebroventricular glial cell line-derived neurotrophic factor (2.5 microg) injection also protected against delayed neuronal death. In addition, pretreatment with glial cell line-derived neurotrophic factor gave significant protection against apoptotic cell death induced by brain ischemia in the hippocampal CA1 region, as determined by in situ staining for DNA fragmentation. These findings suggest that glial cell line-derived neurotrophic factor plays an important role in delayed neuronal death induced by brain ischemia.
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PMID:Glial cell line-derived neurotrophic factor protects against delayed neuronal death after transient forebrain ischemia in rats. 1019 1

It has previously been reported that the beta(1)-adrenoceptor antagonist, betaxolol, can protect retinal neurones from ischaemia when applied topically. It has further been shown that betaxolol can reduce influx of both sodium or calcium into neurones through interaction at neurotoxin site 2 of the sodium channel and the L-type calcium channel, respectively. The present study sought to further investigate the neuroprotective mode of action of betaxolol in the rat retina. Rats were treated topically with L-betaxolol for 10, 5 and 1 min before ischaemia, induced by raising the intraocular pressure above systolic blood pressure for 45 min. This was followed by reperfusion of 3 or 5 days where L-betaxolol was applied topically twice daily. Ischaemia plus reperfusion caused both a loss of immunoreactivity for choline acetyl transferase (ChAT) and a marked reduction of the b-wave of the electroretinogram (ERG). Treatment, as described, with topical L-betaxolol, completely blunted the effects upon ChAT immunoreactivity and caused a significant reversal of the ERG changes. Furthermore, other rats treated topically with commercially available racemic betaxolol (Betoptic Solution, 0.5%) for 6 hr had raised levels of mRNA for brain derived neurotrophic factor (BDNF) but not for basic fibroblast growth factor (bFGF) in their retinas. The combined data provide further evidence that betaxolol can blunt the effects of ischaemia to the rat retina when applied topically just before the insult. Furthermore, the finding that retinal levels of BDNF mRNA are raised following topical betaxolol treatment shows that not only can this drug reach the retina but that it can also induce changes in expression of factors which are known, themselves, to provide neuroprotection to retinal neurones.
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PMID:Topically applied betaxolol attenuates ischaemia-induced effects to the rat retina and stimulates BDNF mRNA. 1113 85

Hepatocyte growth factor (HGF) was originally discovered as a powerful mitogen for hepatocytes. HGF also has been reported to function as a neurotrophic factor as well as an angiogenetic factor. The present study examined the neuroprotective effect of HGF against transient focal cerebral ischemia in rats, in which an anti-apoptotic and an angiogenetic effect of HGF was assumed to contribute to the reduction of the infarct volume. The intraventricular administration of human recombinant HGF prevented neuronal death after 120 min of occlusion in the right middle cerebral artery and the bilateral common carotid arteries. HGF significantly reduced the infarct volume in a dose-dependent manner. In a separate series of experiments, we next histopathologically investigated both the anti-apoptotic effect on neurons and the angiogenetic effect of HGF. A large number of TUNEL positive neurons were observed in the inner boundary of the infarct area in both the control and the vehicle group whereas only a few TUNEL positive neurons were observed in the corresponding area in the HGF group. In the HGF group, Bcl-2 protein was obviously represented in surviving neurons subjected to ischemia. The number of the vascular lamina in HGF group were significantly higher than those in the vehicle group. These data suggest that HGF appears to have an ability to prevent apoptotic neuronal cell death while also possessing an angiogenetic effect in the central nervous system which was affected with transient focal cerebral ischemia.
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PMID:Hepatocyte growth factor reduces the infarct volume after transient focal cerebral ischemia in rats. 1142 24

Hepatocyte growth factor (HGF) was originally discovered as a powerful mitogen for hepatocytes. HGF functions both as a neurotrophic factor as well as an angiogenetic factor. Furthermore, HGF has an anti-apoptotic effect on vascular endothelial cells. The present study examined the neuroprotective effect of HGF after transient focal cerebral ischemia in rats, in which an anti-apoptotic and an angiogenetic effect of HGF was assumed to contribute to the reduction of the infarct volume. The intraventricular administration of human recombinant HGF (90 micrograms) significantly reduced the infarct volume after 120 minutes occlusion of both the right middle cerebral artery (MCA) and the bilateral common carotid arteries (CCAs). In a separate series of experiments, we investigated both the anti-apoptotic effect on neurons and the angiogenetic effect of HGF histopathologically. The number of survival neurons and vascular lumina in the HGF group were significantly higher than those in the vehicle group. A large number of TUNEL positive neurons were observed in the inner boundary of the infarct area in the vehicle group, whereas only a few TUNEL positive neurons were observed in a corresponding area in the HGF group. In the HGF group, Bcl-2 protein was obviously represented in survival neurons as well as in vascular endothelial cells and in glial cells subjected to ischemia. These data suggest that HGF prevents apoptotic neuronal cell death by upregulating the production of Bcl-2 protein and by an angiogenetic effect in the central nervous system which affected transient focal cerebral ischemia.
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PMID:Hepatocyte growth factor reduces infarct volume after transient focal cerebral ischemia in rats. 1145 33

To develop a novel strategy to prevent delayed neuronal death (DND) following transient occlusion of arteries, the gene of hepatocyte growth factor (HGF), a novel neurotrophic factor, was transfected into the subarachnoid space of gerbils after transient forebrain ischemia. Importantly, transfection of HGF gene into the subarachnoid space prevented DND, accompanied by a significant increase in HGF in the cerebrospinal fluid. Prevention of DND by HGF is due to the inhibition of apoptosis through the blockade of bax translocation from the cytoplasm to the nucleus. HGF gene transfer into the subarachnoid space may provide a new therapeutic strategy for cerebrovascular disease.
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PMID:Gene therapy for preventing neuronal death using hepatocyte growth factor: in vivo gene transfer of HGF to subarachnoid space prevents delayed neuronal death in gerbil hippocampal CA1 neurons. 1150 47

The brain has various in vivo neuroprotective mechanisms that allow it to survive for an entire lifetime. As well as neurotrophic factor-mediated inhibition of in vivo apoptotic mechanisms through various protein kinases including Akt and MAP kinase, we propose adding the neuronal death mode switch mechanism observed under the brain ischemic stress to the list of neuroprotective mechanisms. Necrosis occurs when energy or ATP levels are markedly reduced. Lowered ATP levels cause a Na(+)-K(+)-ATPase failure, leading to an osmolysis. On the other hand, sufficient ATP is required for the apoptosome activation. Under the serum-free condition, cortical neurons rapidly die in necrosis. High-glucose treatment converted the cell death mode to apoptosis through an elevation of cellular ATP levels. This treatment also rescued the cell from death due to retinal ischemic injury. These findings suggest the possibility that ischemia-induced neuronal death could be inhibited by some drugs to elevate cellular ATP levels. Neurogenesis in the adult brain is now an important topic in neuroscience. As brain injury is reported to enhance the neurogenesis, this might be also included in the ways of in vivo neuroprotection. As lysophosphatidic acid has various activities to drive neurogenesis, the neurogenesis could also be managed by other drugs to compensate for functions lost by neuronal death.
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PMID:[Neuronal death mode switch and neurogenesis as in vivo neuroprotection]. 1186 61

Recent studies suggest that nerve growth factor (NGF), a neurotrophic factor known to play a crucial role in neurite growth and differentiation, may also modulate vascular cell functions. In the present study, it was investigated whether NGF exhibits an angiogenic effect in a mouse model of hindlimb ischemia induced by femoral artery occlusion. Enzyme-linked immunosorbent assay determination revealed an enhanced endogenous NGF production (378 +/- 100 and 54 +/- 26 pg/g tissue in 7 day ischemic and normoperfused adductor muscles, respectively; P<0.05). Furthermore, exogenous NGF, administered subcutaneously for 7 days in ischemic hindlimb, induced a marked increase of arteriole length density (NGF =41 +/- 5 vs. Saline=22 +/- 4 mm/mm(3); P<0.05). However, capillaries were not significantly increased (NGF =1035 +/- 182 vs. Saline= 829 +/- 60 mm/mm(3); P>0.05). In conclusion, the present study provides first evidence that NGF exerts angiogenic properties in vivo.
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PMID:Nerve growth factor induces angiogenic activity in a mouse model of hindlimb ischemia. 1195 May 5

In mammals, including humans, the subventricular zone of the lateral ventricle and the subgranular zone of the dentate gyrus contain neural stem cells, which continue to proliferate even in adulthood and give rise to new neurons. Neurogenesis in these areas is enhanced by brain insults. Brain-derived neurotrophic factor (BDNF) promotes neuronal survival and differentiation during the development of the nervous system. In the adult intact brain, BDNF administration in the lateral ventricle or ventricular zone stimulates neurogenesis in several forebrain areas. Here we show that intrahippocampal transduction of recombinant adeno-associated virus carrying the BDNF gene giving rise to levels of BDNF protein sufficient to induce a functional response inhibits the formation of new dentate granule cells triggered by global forebrain ischemia in rats. Our data indicate that long-term delivery of a neurotrophic factor, which is considered as a novel neuroprotective strategy for human brain diseases, may attenuate intrinsic neuroregenerative responses.
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PMID:Suppression of insult-induced neurogenesis in adult rat brain by brain-derived neurotrophic factor. 1242 5

We studied the spatial and temporal expression of BDNF immunoreactivity and mRNA in the hippocampal formation after transient forebrain ischemia in gerbils. Our study demonstrated that in the vulnerable CA1 neurons, there was a prolonged expression disparity between BDNF immunoreactivity and mRNA and the BDNF level was reduced, in contrast to the ischemia-resistant dentate gyrus neurons that showed transient expression disparity and maintained the BDNF level. This expression disparity of the neurotrophic factor may be related to delayed neuronal death. Double immunostaining showed that reactive astroglia and microglia could express BDNF, suggesting a possible involvement of these cells in the mechanism of neuronal survival after ischemia.
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PMID:Expression disparity of brain-derived neurotrophic factor immunoreactivity and mRNA in ischemic hippocampal neurons. 1248 90

Nerve growth factor was the first identified protein with anti-apoptotic activity on neurons. This prototypic neurotrophic factor, together with the three structurally and functionally related growth factors brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT3) and neurotrophin-4/5 (NT4/5), forms the neurotrophin protein family. Target T cells for neurotrophins include many neurons affected by neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis and peripheral polyneuropathies. In addition, the neurotrophins act on neurons affected by other neurological and psychiatric pathologies including ischemia, epilepsy, depression and eating disorders. Work with cell cultures and animal models provided solid support for the hypothesis that neurotrophins prevent neuronal death. While no evidence exists that a lack of neurotrophins underlies the etiology of any neurodegenerative disease, these studies have spurred on hopes that neurotrophins might be useful symptomatic-therapeutic agents. However first clinical trials led to variable results and severe side effects were observed. For future therapeutic use of the neurotrophins it is therefore crucial to expand our knowledge about their physiological functions as well as their pharmacokinetic properties. A major challenge is to develop methods for their application in effective doses and in a precisely timed and localized fashion.
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PMID:Neurotrophins. 1257 26


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