UMLS:C0022116 - FACTA Search

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

The effect of Trimetazidine (TMZ) as a potential neuroprotectant against stroke was studied in the gerbil model of transient forebrain global ischemia. Animals were subjected to a 5-min period of ischemia and assessed 4 and 21 days later. Gerbils were divided into two groups: in group one, gerbils were treated with TMZ at a dose of 25 mg/kg given by intraperitoneal injection prior to ischemia. In group two, gerbils were treated with TMZ at a dose of 25 mg/kg given intraperitoneally after ischemia. Saline-injected gerbils served as controls. Histological evaluation of neuronal damage was carried out using the silver staining technique in gerbils 4 and 21 days after the start of the experimental protocol. Behavioral functions were assessed in gerbils from the 14th to the 21st day after the start of the experimental protocol using the Morris water maze test. Results obtained from this study showed no significant difference between saline treated TMZ-treated gerbils when TMZ was administered after ischemia. When TMZ was administered prior to ischemia, there was a reduction in neuronal damage although it did not reach statistical significance and a statistically significant improvement in behavior. We conclude that TMZ shows signs of promise as a neuroprotective agent, and further studies should look at pre-treatment with different doses and different times.
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PMID:Trimetazidine as a potential neuroprotectant in transient global ischemia in gerbils: a behavioral and histological study. 1184 66

In the brain apoptosis may occur as a physiological phenomenon during periods of programmed cell death as well as under pathological conditions such as ischemia, trauma, tumor, and degenerative diseases. While the definition of apoptotic cell death was originally based on ultrastructural alterations, the detection of DNA double-strand breaks has become an important feature in studies of apoptosis. Currently, the terminal transferase-mediated dUTP nick-end labeling (TUNEL) procedure is widely used for detection of apoptotic cell death. However, there is a growing body of evidence to suggest that the TUNEL staining does not label apoptotic alterations exclusively. Therefore, a new staining procedure was developed combining TUNEL methodology with pre-embedding nanogold labeling to detect DNA double-strand breaks in individual cells by electron microscopy and assess the accompanying ultrastructural alterations. In vitro DNAse-treated vibratome sections (thickness, 20 micro m) from normal adult rat brains were used to develop the staining procedure consisting of the following steps: (i) TUNEL staining of free-floating vibratome sections using fluorescein isothiocyanate (FITC)-labeled UTP, (ii) conversion of the fluorescence signal into an electron-dense signal using an anti-FITC antibody coupled with ultrasmall (diameter, 0.8 nm) gold particles followed by silver enhancement, and (iii) osmification, embedding in Spurr resin and cutting of ultrathin sections. Early postnatal brain tissue was used to study physiologically occurring apoptotic cell death. Under these conditions different patterns of gold staining were observed probably representing different states of cellular decay along the apoptotic avenue. Severe focal brain ischemia was studied as a pathological situation in which intense TUNEL staining occurs. Under these conditions TUNEL labeling of cells was regularly observed in conjunction with ultrastructural alterations indicative of necrosis. These results suggest that under pathological conditions apoptosis and necrosis are not mutually exclusive mechanisms but rather may occur concurrently along a continuum in which cell death occurs.
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PMID:Pre-embedding immunogold labeling of TUNEL stain enables evaluation of DNA strand breaks and ultrastructural alterations in individual cells of neuronal tissue. 1241 Mar 84

The aim of the present experiment was to study the influence of +Gz acceleration (head-to-foot inertial forces) onset on cerebral oxygenation changes (cerebral oxy- and deoxy-hemoglobin) and cerebral blood volume (CBV) in order to evaluate the role of cerebral hypoxemia and ischemia in the appearance of +Gz-induced loss of consciousness (G-LOC). We used five rhesus monkeys which were equipped with near infrared spectroscopy optodes fixed onto the parietooccipital cranial bone. G-LOC (isoelectric electrocorticogram) was detected with silver balls electrodes in contact with the dura matter. The animals were centrifuged up to +12 Gz with two onset rates (0.1 and 3 G/s). Cerebral deoxy-hemoglobin increased significantly (max: +30 +/- 6% of control, P < 0.01) only during the 0.1 G/s run. At G-LOC, CBV changes were not related to G-onset rate (P = 0.30; mean change: -32 +/- 6% of control). We conclude that cerebral ischemia is the main mechanism in the occurrence of G-LOC.
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PMID:Cerebral hemodynamics and brain oxygen changes related to gravity-induced loss of consciousness in rhesus monkeys. 1256 42

Moderate hypothermia and application of brain-derived neurotrophic factor (BDNF) have separately been identified as neuroprotective strategies in experimental cerebral ischemia. To assess their separate and combined effects on striatal glutamate release in the hyperacute phase of stroke, we inserted microdialysis probes into the striatum of rats 2 h before permanent middle cerebral artery occlusion (MCAO). The animals (N = 28) were randomly assigned to one of four treatment strategies commencing 30 min after MCAO: (1) hypothermia at 33 degrees C (n = 7); (2) intravenous BDNF infusion [300 microg/(kg/h) for 2 h, n = 7]; (3) combination of hypothermia and BDNF (n = 7); (4) control group (saline, n = 7). Infarct size at 5 h after MCAO was assessed with the silver-staining method. Total infarct volume was significantly reduced in the hypothermia (202.7 +/- 3.5 mm(3), P = 0.0002) and BDNF group (206.5 +/- 6.9 mm(3), P = 0.0006) as compared to control group (254.4 +/- 9.3 mm(3)). In the combination group, infarct size was further reduced with overall significance in post hoc tests (157.3 +/- 6.2 mm(3), P < 0.0001). Postischemic glutamate concentrations in the control group constantly remained significantly higher than in all other treatment groups. At 255 and 270 min after MCAO, striatal glutamate in the combination group decreased significantly more than in animals treated with hypothermia or BDNF alone.Combining hypothermia and BDNF therapy in the acute stage of ischemia has a synergistic effect in attenuating striatal glutamate release and reducing early infarct size.
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PMID:Hypothermia and brain-derived neurotrophic factor reduce glutamate synergistically in acute stroke. 1473 12

The background and mechanisms of ischemic acute tubular necrosis are still essentially unclarified. Therefore a quantitative morphological technique was applied for evaluation of the early structural changes in different fractions of the proximal convoluted tubule in the rat renal cortex. In male pentothal-anesthetized Wistar rats (body weight 200-250 g) ischemia of the right kidney was obtained by clamping (clamp diameter 0.15 mm) the ipsilateral renal artery for varying periods of time (10 min to 6 h) followed by removal and instant freezing of the kidney in isopentane at -165 degrees C and subsequent freeze-substitution in alcohol. The microscopic slides from the kidneys were silver methenamine-PAS stained. In the segments of the proximal convoluted tubules of the nephrons, presence of nuclear pyknosis, places of denuded basement membranes and presence of exfoliated tubular cells were counted. The results were statistically treated for comparison between the extent of damage in the initial postglomerular fraction and the later tubular loops. All three parameters showed a systematic, statistically significant increased number of lesions in the initial fraction of the proximal convoluted tubule versus the subsequent loops. The distribution of the structural lesions is in accordance with the previously reported presence of a tubulo-capillary counter-current flow in the proximal convoluted tubule and, when related to the highly variable oxygen tension in the normal renal cortex of the rat, indicates that the peculiar location of the early lesions might well be determined by these functional conditions.
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PMID:Early segmental changes in ischemic acute tubular necrosis of the rat kidney. 1515 61

Morphological evidence of apoptosis in transient forebrain ischemia is controversial. We therefore investigated the time sequence of apoptosis-related antigens by immunohistochemistry and correlated it with emerging nuclear patterns of cell death in a model of transient forebrain ischemia in CA1 pyramidal cells of the rat hippocampus. The earliest ischemic changes were found on day 2 and 3, reflected by an upregulation of phospho-c-Jun in a proportion of morphologically intact CA1 neurons, which matched the number of neurons that succumbed to ischemia at later time points. At day 3 and later 3 ischemic cell death morphologies became apparent: pyknosis, apoptosis-like cell death and necrosis-like cell death, which were confirmed by electron microscopy. Activated caspase-3 was present in the vast majority of cells with apoptosis-like morphology as well as in a small subset of cells undergoing necrosis; its expression peaked on days 3 to 4. Silver staining for nucleoli, which are a substrate for caspase-3, revealed a profound loss of nucleoli in cells with apoptosis-like morphology, whereas cells with necrosis-like morphology showed intact nucleoli. Overall, cells with apoptosis-like morphology and/or caspase-3 expression represented a minor fraction (<10%) of ischemic neurons, while the vast majority followed a necrosis-like pathway. Our studies suggest that CA1 pyramidal cell death following transient forebrain ischemia may be initiated through c-Jun N-terminal kinase (JNK) pathway activation, which then either follows an apoptosis-like cell death pathway or leads to secondary necrosis.
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PMID:Ischemia leads to apoptosis--and necrosis-like neuron death in the ischemic rat hippocampus. 1560 89

Fluoro-Jade B, a marker of degenerating neurons, was used to label histopathological changes in the rat spinal cord after transient ischemia and ischemic preconditioning (IPC). To characterize postischemic neurodegenerations and consequent neurological changes, a particular attention was paid to the standardization of ischemic conditions in animals of both groups. 1. The control ischemic rats were submitted to a reversible occlusion of descending aorta by insertion and subsequent inflation of a 2F Fogarty catheter for 12 min. 2. In the IPC rats, an episode of short 3 min occlusion and 30 min reperfusion preceded the 12 min ischemia. Postischemic motor function testing (ambulation and stepping) was provided repeatedly for evaluation of neurological status 2 h and 24 h after surgery and at the end of postischemic survival, i.e. after 48 h. Fluoro-Jade B staining was used to demonstrate degenerated neurons. In the control rats, neurological consequences of histopathological changes in lumbosacral spinal cord, manifested as paraplegia, were present after 12 min ischemia. Thus, numbers of degenerated Fluoro-Jade B positive cells were visible in gray matter of the most injured L(4)-S(2) spinal cord segments. Slight motor function impairment, consequential from significant decreasing in Fluoro-Jade B-positivity in the L(4)-S(2) spinal cord segments of the IPC rats, was considered the pathomorpfological evidence that IPC induces spinal cord tolerance to ischemia. Our results are consistent with the previously published silver impregnation method for histopathological demonstration of ischemic degeneration.
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PMID:Fluoro-Jade B evidence of induced ischemic tolerance in the rat spinal cord ischemia: physiological, neurological and histopathological consequences. 1590 88

Previously, we identified proteins released from degenerating cultured cortical neurons as novel cerebrospinal fluid (CSF) markers for acute brain injury in the rat. Here, we investigate relationships between CSF changes in these novel markers and the severity of acute ischemic brain injury. Rats underwent sham surgery or 3,6,8, or 10 mins of transient global forebrain ischemia. At 48 h after insult, CSF levels of 14-3-3beta, 14-3-3zeta, and calpain cleavage products of alpha-spectrin and tau were quantified. Regional acute neurodegeneration was assessed by Fluoro-Jade and silver impregnation staining, and confirmed by immunohistochemical detection of the activation of calpain and caspase, cysteine proteases involved in neurodegenerative signaling. Ischemic neurodegeneration and activation of at least one cysteine protease were observed in the hippocampal CA1 sector, dentate hilus, caudate nucleus, parietal cortex, thalamus, and inferior colliculus. As expected, the total number of degenerating cells increased as a function of ischemia duration. Cerebrospinal fluid levels of the four marker proteins increased markedly after ischemia, and rose in proportion with its duration. Irrespective of the length of ischemia, CSF levels of the neuron-enriched proteins 14-3-3beta and calpain-cleaved tau correlated significantly with the magnitude of acute ischemic neurodegeneration. Additionally, CSF levels of the two proteins correlated with one another. These results show that certain proteins released from degenerating neurons are CSF markers for brain injury in the rat whose levels reflect the severity of acute ischemic neurodegeneration. Measurement of 14-3-3beta and calpain-cleaved tau may be useful for the minimally invasive diagnosis, prognosis, and therapeutic evaluation of acute brain damage.
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PMID:Novel surrogate markers for acute brain damage: cerebrospinal fluid levels corrrelate with severity of ischemic neurodegeneration in the rat. 1590 99

Calpain-1 is a ubiquitous intracellular Ca2+-activated protease, which has been implicated in the pathogenesis of reversible myocardial depression (i.e. myocardial stunning) that follows ischemia and reperfusion via myofibrillar protein degradation. However, the target proteins of this degradative process in the human myocardium have not yet been identified. In order to compare the levels of Calpain-1 susceptibility within a set of human myofibrillar proteins (titin, alpha-fodrin, desmin, troponin T (cTnT), troponin I (cTnI) and alpha-actinin), crude left ventricular tissue homogenates were incubated for 0.5, 15, 30, 60 or 120 min in the presence of Calpain-1 (1 U or 5 U). Differences in the kinetics and extents of protein degradation were subsequently evaluated by using silver-stained SDS-polyacrylamide gels and Western immunoblot analyses. These assays revealed myofibrillar proteins with high (titin and alpha-fodrin), moderate (desmin and cTnT), or low (cTnI and alpha-actinin) relative Calpain-1 susceptibilities. The level of phosphorylation of cTnI did not explain its relatively low Calpain-1 susceptibility. Moreover, the molecular mass distributions of the truncated alpha-fodrin, desmin and cTnI fragments resulting from Ca2+-dependent autoproteolysis exhibited marked similarities with those of their Calpain-1-clipped products. These in vitro results shed light on a number of structural (titin, alpha-fodrin, desmin and alpha-actinin) and regulatory (cTnT and cTnI) proteins within the contractile apparatus as potential targets of Calpain-1. Their degradation may contribute to the development of postischemic stunning in the human myocardium.
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PMID:Calpain-1-sensitive myofibrillar proteins of the human myocardium. 1618 82

Recent studies show that bisphosphonates can decrease the development of femoral head deformity following ischemic osteonecrosis by inhibiting osteoclast-mediated bone resorption. Given the potential new indication, improved understanding of pharmacokinetics of bisphosphonates as it applies to the infarcted head would be beneficial. The purpose of this study was to investigate the local bioavailability and the distribution of ibandronate in the infarcted head at the avascular and vascular phases of the disease process. Ischemic osteonecrosis of the femoral head was surgically induced in 15 piglets. One, 3, and 6 weeks following the induction of ischemia, which represent various stages of revascularization and repair, 14C-labeled ibandronate was administered intravenously. Twenty-four hours following 14C-drug administration, the level of radioactivity and its distribution in the infarcted heads were determined using liquid scintillation analysis and autoradiography. A significant correlation was found between the extent of revascularization and the level of radioactivity measured in the infarcted heads (r=0.80, P<0.05). The radioactivity level in the infarcted heads measured by liquid scintillation was similar to the negative controls at 1 week when revascularization was absent, but it increased significantly at 6 weeks when extensive revascularization was present (P<or=0.00004). Autoradiographic assessment showed similar silver grain counts in the infarcted heads compared to the background at 1 week. At 3 weeks, a significant increase in the silver grain count was observed in the necrotic regions of the infarcted heads compared to the background (P=0.001) even though only a small area of the heads (2%) was found to be revascularized, suggesting diffusion of 14C-drug from the revascularized to the non-revascularized areas of the head. At 6 weeks, extensive 14C-drug binding was observed in the areas of revascularization with preferential binding of 14C-drug to the newly formed bone compared to the remaining necrotic bone (P=0.000001). These results indicate that revascularization and repair produce significant alteration of local bioavailability and distribution of ibandronate in the infarcted head. To our knowledge, this is the first study to examine the local bioavailability and distribution of bisphosphonate in the infarcted head. Current findings have important implications with regard to the timing and dosing of bisphosphonate after the onset of ischemic osteonecrosis.
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PMID:Local bioavailability and distribution of systemically (parenterally) administered ibandronate in the infarcted femoral head. 1648 Sep 39

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