Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0917798 (cerebral ischemia)
 17,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effects of arachidonic acid on [3H]choline uptake, on [3H]acetylcholine accumulation, and on endogenous acetylcholine content and release in rat cerebral cortical synaptosomes were investigated. Arachidonic acid (10-150 microM) produced a dose-dependent inhibition of high-affinity [3H]choline uptake. Low-affinity [3H]choline uptake was also inhibited by arachidonic acid. Fatty acids inhibited high-affinity [3H]choline uptake with the following order of potency: arachidonic greater than palmitoleic greater than oleic greater than lauric; stearic acid (up to 150 microM) had no effect. Inhibition of [3H]choline uptake by arachidonic acid was reversed by bovine serum albumin. In the presence of arachidonic acid, there was an increased accumulation of choline in the medium, but this did not account for the inhibition of [3H]choline uptake produced by the fatty acid. Arachidonic acid inhibited the synthesis of [3H]acetylcholine from [3H]choline, and this inhibition was equal in magnitude to the inhibition of high-affinity [3H]choline uptake produced by the fatty acid. A K+-stimulated increase in [3H]acetylcholine synthesis was inhibited completely by arachidonic acid. Arachidonic acid also depleted endogenous acetylcholine stores. Concentrations of arachidonic acid and hemicholinium-3 that produced equivalent inhibition of [3H]choline uptake also produced equivalent depletion of acetylcholine content. In the presence of eserine, arachidonic acid had no effect on acetylcholine release. The results suggest that arachidonic acid may deplete acetylcholine content by inhibiting high-affinity choline uptake and subsequent acetylcholine synthesis. This raises the possibility that arachidonic acid may play a role in the impairment of cholinergic transmission seen in cerebral ischemia and other conditions in which large amounts of the free fatty acid are released in brain.
 ...
PMID:Arachidonic acid inhibits choline uptake and depletes acetylcholine content in rat cerebral cortical synaptosomes. 312 67

Lead encephalopathy was induced in suckling rats by administering lead to the mother. The brains were studied by light and electron microscopy, and the results were compared with observations in the human disease as well as in cases of cerebral ischemia in children. In their severe forms, both human and experimental lead encephalopathies are characterized by exudative extracellular edema and perivascular PAS-positive globules. The latter consist of osmiophilic non-membrane-limited cytoplasmic inclusions located, in the rat exclusively and in the human predominantly, in perivascular astrocytes. Intervascular strands are also found in both forms of the disease. In the rat these consist of basement membrane surrounding endothelial cytoplasm. Chemically, experimental lead encephalopathy with morphologically demonstrable edema is associated with an increase in brain water, sodium and serum albumin. Relative to the serum concentration, the increase in water is disproportionately greater than the sodium or albumin. There were no demonstrable changes in chloride or potassium.
 ...
PMID:Electron microscopic and chemical studies of the vascular changes and edema of lead encephalopathy. A comparative study of the human and experimental disease. 435 30

We prospectively evaluated the inflammatory response to acute cerebral ischemia in 57 patients who were seen within 72 hours of ictus. All subjects had cerebrospinal fluid examination, complete blood count, sedimentation rate determination, and body temperature monitoring. Correlation analysis was done between these measurements and infarct volume, which was determined by computed tomography of the brain. We found a positive linear correlation between infarct size and the peripheral white blood cell count, specifically the polymorphonuclear leukocyte count. A relationship was also observed for the cerebrospinal fluid protein level, the gamma globulin level, and the cerebrospinal fluid/serum albumin ratio. The correlations observed presumably reflect the extent of tissue injury and secondary inflammatory response in acute cerebral ischemia.
 ...
PMID:Cerebrospinal fluid and peripheral white blood cell response to acute cerebral ischemia. 763 Dec 6

Cerebral infarction (stroke) is a potentially disastrous complication of diabetes mellitus, principally because the extent of cortical loss is greater in diabetic patients than in nondiabetic patients. The etiology of this enhanced neurotoxicity is poorly understood. We hypothesized that advanced glycation endproducts (AGEs), which have previously been implicated in the development of other diabetic complications, might contribute to neurotoxicity and brain damage during ischemic stroke. Using a rat model of focal cerebral ischemia, we show that systemically administered AGE-modified bovine serum albumin (AGE-BSA) significantly increased cerebral infarct size. The neurotoxic effects of AGE-BSA administration were dose- and time-related and associated with a paradoxical increase in cerebral blood flow. Aminoguanidine, an inhibitor of AGE cross-linking, attenuated infarct volume in AGE-treated animals. We conclude that AGEs may contribute to the increased severity of stroke associated with diabetes and other conditions characterized by AGE accumulation.
 ...
PMID:Neurotoxicity of advanced glycation endproducts during focal stroke and neuroprotective effects of aminoguanidine. 773 77

Focal cerebral ischemia was produced in rats with left middle cerebral artery occlusion for 24 hours. Regional CBF was measured by the 14C-iodoantipyrine technique. The distribution of red blood cells (RBC) and plasma in cerebral microvessels was determined by radioluminography using 51Cr-RBC and 125I-bovine serum albumin, respectively. The mean transit times of RBC and plasma, blood volume, and hematocrit were calculated. The water content was measured by specific gravity. The blood flow was reduced to 2% of the control value in the central core, where the brain edema was the most severe. The blood volume decreased to 25% and the mean transit times of RBC and plasma increased about tenfold. In the outer periphery, where CBF was reduced to 39% but brain edema was not induced, the blood volume was decreased to 76% while the mean transit time of RBC was increased 2.1-fold, being greater than the increase in the plasma transit time. These findings indicate that focal ischemia has variable effects on the blood volume and flow velocities of RBC and plasma in the parenchymal microvessels depending on the depth of blood flow and edema. A decrease in blood flow is probably related to a reduction in the flow velocities of RBC and plasma in the surrounding ischemic tissue rather than to decreased number of perfused capillaries in the ischemic core.
 ...
PMID:Blood volume and flow velocity through parenchymal microvessels in ischemic brain edema of rats. 941 67

Microglial activation and disruption of blood-brain barrier (BBB) are known to occur and contribute to neuronal damages in cerebral ischemic conditions and in some neurodegenerative diseases. To investigate whether a serum factor leaked out from circulation enhances microglial activation, we examined the effect of normal rat serum on superoxide (O2-) production by cultured microglia. Microglia cultured from neonatal rat brains were studied on their O2- production induced by the addition of phorbol myristate acetate by a method of acetyl-cytochrome c reduction. The O2- production was significantly increased by the addition of 0.01% rat serum, and the maximal enhancement was observed at about 0.1% rat serum. After the serum was fractionated using a molecular sieve membrane, we observed the enhancing effect only in a greater molecular weight fraction (>50 kDa). Furthermore, three kinds of bovine serum albumin (BSA) with different purity, and human serum and plasma albumins, also enhanced O2- production to a similar extent to that by rat serum. However, other proteins tested showed no significant effect. The enhancement of O2- production by BSA was observed dose-dependently, and the effect of 50 microg/ml of purified BSA was equivalent to that of 0.1% rat serum, suggesting that albumin itself enhances O2- production by microglia. These results imply that albumin leaked out through impaired BBB may activate microglia and that the potentiation of O2- production by albumin results in the pathogenesis of neuronal damage in cerebral ischemia and some neurodegenerative diseases.
 ...
PMID:Albumin enhances superoxide production in cultured microglia. 941 17

A previous study indicated that diaspirin-crosslinked hemoglobin (DCLHb) decreases cerebral ischemia after subarachnoid hemorrhage. However, the study was limited in that DCLHb was given to animals with an intact vasculature. As extravasated hemoglobin has been implicated in the pathogenesis of cerebral vasospasm, DCLHb in the subarachnoid space might in theory have a detrimental effect on cerebral perfusion after subarachnoid hemorrhage. In the current study, autologous blood was administered into the cistema magna of isoflurane-anesthetized rats. After 30 minutes, the animals received one of the following in the cistema magna (n=8 for each group): The control group received mock cerebral spinal fluid, the "blood" group received autologous blood, the "DCLHb" group received DCLHb, and the "Alb" group received human serum albumin. After 20 minutes, areas of reduced cerebral blood flow (CBF, 0-20 and 21-40 ml/100 g/min) were assessed in five coronal brain sections with 14C-iodoantipyrine. The data were evaluated by analysis of variance. The areas of 0-20 ml/100 g/min CBF were greater in all five brain sections in the Blood group than in the other three groups; were greater in four brain sections in the DCLHb group than in the Control group; and were greater in three brain sections in the Alb group than in the Control group (p < 0.05). The areas of 21-40 ml/100 g/min CBF were greater in three sections in the Blood group than in the other three groups; and were greater in two brain sections in the DCLHb group than in the Alb group (p < 0.05). These data support a hypothesis that subarachnoid blood induces cerebral hypoperfusion, and that although molecular hemoglobin decreases CBF, the potential adverse effects are less than those produced by blood.
 ...
PMID:Subarachnoid molecular hemoglobin after subarachnoid hemorrhage in rats: effect on the area of hypoperfusion. 968 3

We have shown that high-concentration albumin therapy is markedly neuroprotective in focal cerebral ischemia. The present study was conducted to ascertain the degree to which hemodynamic alterations are responsible for this therapeutic effect. Normothermic, physiologically regulated male Sprague-Dawley rats received a 2-h period of middle cerebral artery occlusion (MCAo) by insertion of an intraluminal suture coated with poly-L-lysine. Albumin (25% human serum albumin solution) or vehicle (0.9% sodium chloride) was administered intravenously at a dose of 1% of body weight immediately after suture withdrawal following 2-h MCAo. Local cerebral blood flow (LCBF) was measured autoradiographically with 14C-iodoantipyrine after 1 h of recirculation. Novel image-processing methods were used to compare average LCBF data sets against previously obtained infarction-frequency data on a pixel-by-pixel basis. Albumin therapy reduced mean hematocrit by 42% but produced no other systemic alterations. Pixel-based histopathological analysis revealed large, consistent cortical and subcortical infarcts in saline-treated rats with MCAo; albumin therapy reduced mean cortical infarct volume by 85%. Within regions showing albumin-associated neuroprotection, numbers of pixels having LCBF in the upper ischemic-core flow range (0.12-0.24 ml g-1 min-1) were reduced by 8.6-fold by albumin therapy when compared to saline-treated rats; and numbers of pixels with LCBF in the lower penumbral flow range (0.24-0.36 ml g-1 min-1) were reduced by 3. 1-fold in albumin-treated rats (p=0.04 by repeated-measures analysis of variance). Analysis of the [albumin-saline] 3-dimensional difference-image data set revealed a circumferential zone of statistically significant albumin-associated LCBF increase within the posterior portion of the ischemic hemisphere, surrounding the core-region of prior ischemia. Thus, high-concentration albumin therapy improves local perfusion to regions of critical LCBF reduction. The spatial extent of this LCBF effect, however, appears too small to account fully for the marked neuroprotective efficacy of this therapy. We suggest that other, non-hemodynamic mechanisms may also be contributory.
 ...
PMID:The effect of high-dose albumin therapy on local cerebral perfusion after transient focal cerebral ischemia in rats. 972 10

Nitroxide free radicals are known to protect cells from oxidative damage. Diffusion-weighted and perfusion-weighted magnetic resonance imaging was used to evaluate the effects of polynitroxyl albumin (PNA) in a middle cerebral artery intraluminal suture model of transient focal cerebral ischemia in the rat. Three groups of Sprague-Dawley rats were investigated: (1) PNA (N=6), (2) human serum albumin (N =6), and (3) saline (N=7). The middle cerebral artery was occluded for 2 hours. Treatment was started 30 minutes after induction of ischemia. A total dose of 1% body weight (volume/weight) of PNA (23.5 mg/dL protein and 110 mmol/L nitroxide), albumin (23.5 mg/dL), or saline was injected intravenously at three time points: 0.5% at 0.5 hours, 0.25% at 2 hours (i.e., just before reperfusion), and 0.25% at 4 hours after occlusion. Six sets of diffusion- and perfusion-weighted magnetic resonance images were acquired throughout the 2 hours of ischemia and the 2 hours of reperfusion. The rats were killed at 24 hours, and the brains were stained with 2,3,5-triphenyltetrazolium chloride (TTC). Diffusion-weighted imaging showed that the growth of the ischemic lesion was suppressed in the PNA-treated group. The 4 hours diffusion-weighted imaging--derived hemispheric lesion volume in the PNA-treated group (25%+/-9%) was significantly smaller than that in the saline-treated (43%+/-13%; P=0.016) or albumin-treated groups (38%+/-6%; P=0.017). A larger difference was observed for the 24-hour TTC-derived lesion volumes in the PNA (8%+/-7%), saline (35%+/-8%; P < 0.001), and albumin (31%+/-6%; P < 0.001) groups. Perfusion-weighted imaging demonstrated a marked improvement in cerebral perfusion in the PNA-treated group during ischemia and reperfusion. In conclusion, treatment with PNA results in an improvement in perfusion and a reduction of infarct volume in a model of transient focal cerebral ischemia in the rat.
 ...
PMID:Polynitroxyl albumin reduces infarct size in transient focal cerebral ischemia in the rat: potential mechanisms studied by magnetic resonance imaging. 974 Jan 6

Accumulation of serum protein has been demonstrated in injured brain cells following vasogenic brain edema. The present study was conducted to test whether this phenomenon is also observed in apoptotic cells as well as in necrotic cells. Apoptotic cell death has been implicated in a variety of brain injuries, including ischemia and trauma. Cold injury and focal cerebral ischemia-reperfusion were used to induce both vasogenic edema and apoptotic cell death. Evans blue extravasation was used to determine the cellular accumulation of serum albumin. Apoptotic cell death was evaluated by both morphological alterations and by terminal deoxynucleotidyl transferase-mediated uridine 5'-triphosphate-biotin nick end labeling (TUNEL) staining. Evans blue accumulation in cells was observed not only in the surrounding zone of the lesion after cold injury and in the entire ischemic area after focal ischemia, but was also detected in the regions remote from the primary injury site. Some of these cells demonstrated nuclei fragmentation. TUNEL staining confirmed that apoptosis was induced in the region where apoptotic cells were morphologically detected. These observations suggest that accumulation of the extravasated serum component is accompanied by apoptotic cell death following vasogenic brain edema.
 ...
PMID:Cellular accumulation of extravasated serum protein and DNA fragmentation following vasogenic edema. 981 38


<< Previous 1 2 3 4 5 Next >>