Biomedical subjects

S Ueki

Publications and source records attributed to S Ueki.

At least 19 recordsLinked to original sources

PubMed1999

12-hydroxy-5Z, 8Z, 10E, 14Z, eicosatetraenoic acid (12-HETE) stimulates cAMP production in normal human fibroblasts.

We report here that the 12-lipoxygenase metabolite of arachidonic acid, 12-hydroxy-5Z, 8Z, 10E, 14Z, eicosatetraenoic acid (12-HETE), stimulates cAMP production in human fibroblasts among various cultured cell lines tested. Although 12-HETE seemed to stimulate the phospholipase C (PLC)-protein kinase C (PKC) system, inhibitors against PLC and PKC did not reduce the cAMP production induced by 12-HETE, indicating that the activation of PLC-PKC system is not positively coupled with the stimulation of cAMP production. On the other hand, the cAMP production induced by 12-HETE was dependent on the Ca2+/calmodulin system in the cells. The results suggest that 12-HETE specifically stimulates Ca2+/calmodulin-dependent adenylyl cyclase to increase cAMP level in the fibroblasts.

1-Methyl-3-isobutylxanthine↗

PubMed1999

Gastroprokinetic activity of nizatidine during the digestive state in the dog and rat.

The present study was undertaken to clarify a prokinetic activity of nizatidine (CAS 76963-41-2) during the digestive state as well as gastric emptying of a solid test meal in comparison with cimetidine (CAS 51481-61-9), famotidine (CAS 76842-35-6) and cisapride (CAS 81098-60-4). Intravenous administration of nizatidine (0.3-3 mg/kg) enhanced the motility of the gastric antrum and duodenum during the digestive state. With cimetidine (1-10 mg/kg) and famotidine (0.1-1 mg/kg) enhancement of gastric motility was observed only with the highest dose of cimetidine, and famotidine had no effect. Marked enhancement of gastric motility was observed with cisapride (0.1-0.5 mg/kg). After intraduodenal administration of nizatidine (10 and 20 mg/kg) and cisapride (0.25 and 0.5 mg/kg), they also amplified the contractile activity of the gastric antrum. Gastric emptying of a solid test meal was accelerated by intraperitoneal administration of nizatidine (1-10 mg/kg) to the same extent as cisapride (0.1-1 mg/kg). In addition, even in a model of delayed gastric emptying induced by clonidine, nizatidine, like cisapride, improved the rate of gastric emptying. Neither cimetidine (3-30 mg/kg) nor famotidine (0.3-3 mg/kg) affected the gastric emptying of a solid meal or delayed gastric emptying. These results suggest that nizatidine enhanced gastric motility even during the digestive state, and accelerated gastric emptying of a solid meal, similar to cisapride. Furthermore, nizatidine improved clonidine-induced delayed gastric emptying. These prokinetic activities of nizatidine may by useful for the treatment of abdominal symptoms due to dysmotility and delayed gastric emptying in patients with gastritis and non-ulcer dyspepsia (NUD). In comparison with famotidine and cimetidine, nizatidine may be different from other histamine H2-receptor antagonists and has unique properties other than its gastric antisecretory activity.

Animals↗

PubMed1998

The 'ligand-induced conformational change' of alpha 5 beta 1 integrin. Relocation of alpha 5 subunit to uncover the beta 1 stalk region.

Integrin heterodimers undergo a conformational change upon the binding of ligand to their extracellular domains. An anti-beta1 integrin monoclonal antibody AG89 can detect such a conformational change since it recognizes a ligand-inducible epitope in the stalk-like region of beta1 subunits. The binding of a 125I-labeled AG89 Fab fragment to alpha5 beta1 integrins on K562 cells was assessed and analyzed by the Scatchard method. High affinity binding sites for AG89 are present on cells treated with ligand peptide. In addition, results revealed that cells treated with EDTA also express AG89 binding sites with the same affinity although the number of binding sites is 4-fold lower. AG89 immunoprecipitated alpha5 beta1 complexes from surface-labeled K562 cells treated with ligand peptide. By contrast, it immunoprecipitated only beta1 chains when the ligand peptide was absent, suggesting that high affinity binding sites on EDTA-treated cells are associated with non-functional beta1 monomer. Additional studies show that the epitope for AG89 is constitutively exposed on mutant beta1 that cannot complex with alpha5. These data suggest that the AG89 epitope is masked by the alpha5 subunit. Ligand binding and integrin activation may uncover the beta1 stalk region by triggering a conformational shift of alpha5 relative to beta1.

Animals↗

PubMed1997

Classification of 'activation' antibodies against integrin beta1 chain.

We compared the effects of two anti-beta1 integrin activating antibodies, TS2/16 and AG89, on K562 cell adhesion to fibronectin. Though both antibodies effectively induced cell adhesion, the EC50 for AG89 was more than 200-fold higher than that for TS2/16. Scatchard analysis of the data from [125I]Fab fragment binding to the cells revealed that the TS2/16 epitope is exposed constitutively on all the beta1 integrin molecules, while only 3% of the beta1 integrins on resting K562 cells bear the AG89 epitope. Calculation of the actual number of each antibody bound to the cell during the cell adhesion assay revealed that induction of cell adhesion can be accomplished by binding much fewer AG89 molecules compared to TS2/16. Thus, AG89 and TS2/16 represent distinct classes of anti-integrin activating antibodies that show completely different binding characteristics as well as different activation effects on the integrin molecule upon binding.

Antibodies, Monoclonal↗

PubMed1997

Ameliorating effects of rolipram on experimentally induced impairments of learning and memory in rodents.

The effects of rolipram, a cAMP-specific phosphodiesterase (phosphodiesterase 4) inhibitor, on experimentally-induced amnesia were examined using a 3-panel runway paradigm in rats and a passive avoidance task in mice. Scopolamine, cerebral ischemia induced by four-vessel occlusion and electric convulsive shock impaired working memory in the 3-panel runway task. Rolipram at 0.1 mg/kg reduced the increase in errors induced by scopolamine or cerebral ischemia. Rolipram at 0.32 mg/kg also reduced the increase in errors induced by electric convulsive shock. Dibutyryl cAMP also had similar effects in 3-panel runway experiments. In the passive avoidance task, rolipram reversed the impairments of the avoidance response induced by scopolamine, cycloheximide and electric convulsive shock at 10, 10 and 3 mg/kg, respectively. These results indicate that rolipram ameliorates impairments of learning and memory in rats and mice, and suggest that rolipram might ameliorate the impairments of learning and memory by elevating cAMP levels.

Animals↗

PubMed1996

Dual functions of transglutaminase in novel cell adhesion.

Transglutaminases (TGases) are enzymes which catalyze cross-link formation between glutamine residues and lysine residues in substrate proteins. In the present study, we report for the first time that a representative enzyme, blood coagulation factor XIIIa (FXIIIa), is capable of mediating adhesion of various cells. When coated on plastic surfaces FXIIIa promoted adhesion and spreading of various cells of both normal and tumor origin, in a concentration-dependent manner. The adhesion was not inhibited by antibodies against possible contaminants in the enzyme preparation such as fibronectin and vitronectin, but was completely inhibited by a polyclonal antibody against the enzyme. Therefore, if there were any contaminating cell adhesive substrates in the enzyme preparation, they cannot account for the observed cell adhesion to the enzyme; FXIIIa itself mediates the cell adhesion. Furthermore, phosphorylation of tyrosine residues in 120 kDa and 70 kDa proteins was clearly shown in human fibroblasts adhering to the enzyme. Formation of actin stress fibers was also unambiguously observed in the adhering cells. These biochemical reactions, which are also observed when cells adhere to a typical cell adhesion protein, fibronectin, are believed to be of importance in the process of cell adhesion. This adhesion activity of FXIIIa was dependent on its TGase activity, because both a modification of the active center cysteine with iodoacetamide and the addition of ammonium ion abolished the cell adhesion activity along with the enzyme activity. The cell adhesion to fibronectin, however, was not affected by these treatments. The effects of various anti-integrin antibodies suggested that both alpha v beta 3 and beta 1 family integrins participated in the cell adhesion to FXIIIa. Taken together, these data demonstrate for the first time that there is a unique TGase activity-mediated cell adhesion. This novel function of the enzyme may be of physiological importance.

Alkylating Agents↗

PubMed1995

Spin-lattice relaxation times of water in polarized and depolarized rabbit vagus nerves.

Spin-lattice relaxation times (T1) of intracellular water of the nonmyelinated fibers of rabbit cervical vagus nerve were measured using a paramagnetic shift reagent, s-FDF. Spin-lattice relaxation decay curves were composed of the fast (T1,F) and slow (T1,S) relaxation components. The mean values of T1,F and T1,S in the polarized nerve fibers at 25 degrees C were 0.12 +/- 0.04 and 0.61 +/- 0.13 sec., respectively, and their fractions were 0.71 +/- 0.07 and 0.29 +/- 0.07, respectively (n = 21). On the other hand, those values in the depolarized nerve fibers were 0.16 +/- 0.01 sec., 0.77 +/- 0.17 sec., 0.77 +/- 0.10 and 0.23 +/- 0.10, respectively (n = 15). T1,F and T1,S for the depolarized nerve fibers were significantly elongated (P < 0.01).

Animals↗

PubMed1995

Identification of factor-XIIIa-reactive glutaminyl residues in the propolypeptide of bovine von Willebrand factor.

von Willebrand factor is a large multimeric plasma protein which plays important roles in platelet aggregation, blood coagulation and probably also in the adhesion of endothelial cells. A 100-kDa propeptide, called the propolypeptide of von Willebrand factor (pp-vWF), is generated during biosynthesis. We found that pp-vWF served as a substrate for transglutaminases including human factor XIIIa and guinea pig liver transglutaminase [Usui, T., Takagi, J. & Saito, Y. (1993) J. Biol. Chem. 268, 12311-12316]. As such, it could form cross-linked copolymers with the extracellular matrix protein, laminin, making it all the more likely that pp-vWF plays a role in cell adhesion phenomena [Takagi, J., Sudo, Y., Saito, T. & Saito, Y. (1994) Eur. J. Biochem. 222, 861-867]. In this work, we identified the Gln residues in pp-vWF specifically reacting with blood coagulation factor XIIIa as amine acceptors. The fluorescent amine, dansylcadaverine, was employed for labeling the enzyme-reactive sites of the protein. Following partial proteolysis, fragments containing the labeled Gln residues were isolated by passage through an anti-dansyl affinity chromatographic column. Amino acid sequence analyses of the fragments revealed that, out of about 40 Gln residues in pp-vWF, only four could be modified in the factor-XIIIa-catalyzed reaction.

Amino Acid Sequence↗

PubMed1995

Histological study of the circulatory system of human dental pulp from individuals under local anesthesia and electro-acupuncture.

A transmission electron microscopic (TEM) study was conducted on dental pulp obtained from patients under acupuncture or infiltration local analgesia. It was difficult to differentiate lymphatic circulation in the dental pulp that received infiltration anesthesia, because the vessels were constricted, congested, and showed stasis and thrombosis. On the other hand, the dental pulp that received acupuncture showed normal arterioles, capillaries, and venules, as well as some lymph capillaries and small efferent lymphatic vessels that measured about 8 microns and 100 microns in diameter, respectively. The lymphatic endothelial walls had many intercellular gaps, an imperfect basal lamina, and a few discontinuous pericytes. Between the openings in the lymphatic vessels, there were bundles of junctional filaments extending towards the dental pulp connective tissue. Therefore, the lymphatic system, which contains mainly B-3-alpha capillaries, is a leaky tissue for regulating fluid in the dental pulp.

Acupuncture Analgesia↗

PubMed1994

Inhibition of phase III activity by acid in canine stomach.

Very few phase III activity of the interdigestive migrating contractions (phase III) occurs in the stomach of fasted duodenal ulcer patients. But the mechanism is not well understood. In this study, we studied the effect of gastric and duodenal acidification on the spontaneous phase III activity in the upper gastrointestinal tract of conscious dogs. Gastric and duodenal motor activity in 5 conscious dogs was monitored by means of chronically implanted force transducers. Intragastric pH changes were measured by placing a pH glass electrode in the gastric antrum. Intragastric and intraduodenal acidification was achieved by i.v. infusion of histamine, and by intragastric and intraduodenal instillation of acidic solutions of different pHs. The plasma motilin concentrations were measured by radioimmunoassay. Histamine (40 micrograms/kg/h) inhibited spontaneous phase III activity, but the histamine-induced inhibition was completely prevented by pretreatment with famotidine, a potent histamine H2 receptor antagonist (0.3 mg/kg, i.v.). Intragastric acidification at pH 1.0 strongly inhibited spontaneous phase III activity, but an acidic solution at pH 2.0 had no effect in inhibiting phase III activity. Intraduodenal acidification at pH 1.0 also inhibited spontaneous phase III activity. Histamine injection and gastric and duodenal acidification at pH 1.0 strongly suppressed motilin release. It is concluded that gastric and duodenal acidification at pH 1.0 inhibits the occurrence of the spontaneous phase III activity, and the suppression of endogenous release of motilin due to gastric and duodenal acidification at pH 1.0 is involved in this inhibitory mechanism.

Animals↗

PubMed1994

Topography of commissural fibers in the corpus callosum of the cat: a study using WGA-HRP method.

The topography of the commissural fibers in the corpus callosum (CC) of the cat was systematically investigated using the WGA-HRP method. WGA-HRP was injected into various parts of the cerebral cortex and locations of WGA-HRP-stained commissural fibers in the CC were examined. Commissural fibers were arranged in a topological fashion in the CC. Cortical areas rostral to the cruciate sulcus (CrS), corresponding to motor or premotor cortices, projected fibers into the genu of the CC, while fibers from the cortex caudal to the CrS passed through the CC slightly caudal to the genu. When WGA-HRP was injected into the lateral gyrus (LG), it was observed that fibers from the anterior LG passed through the anterior one-third of the CC, whereas those from the posterior LG passed through or near the splenium, and fibers from the middle LG passed between those from the anterior and posterior LG. Similarly, the suprasylvian gyrus (SSG) projected commissural fibers in the CC in a rostrocaudal topological manner. Fibers from the anterior SSG passed through the anterior one-third of the CC, and those from the middle SSG through the middle one-third of the CC and upper part of the splenium. Injection into the most posterior part of the middle SSG revealed fibers passing through the caudal end of the splenium. Callosal fibers from the anterior SSG were focused on in this study, because this area (area 2v) is considered one of the vestibular projection cortices and is an area of special interest to the authors. Callosal fibers from the anterior SSG were observed to pass through the anterior one-third of the body of the CC. When WGA-HRP was injected into auditory areas, fibers from the anterior and middle ectosylvian gyri (ESG) were observed to pass through the posterior one-third of the body of the CC or through the splenium, while fibers from the posterior ESG passed through the splenium. WGA-HRP was also injected into the cingulate gyrus (CiG). Fibers from the anterior CiG (area 24) passed through the anterior portion of the CC while those from the posterior CiG (area 23) passed through the posterior portion of the CC.

Animals↗

PubMed1994

Olfactory bulbectomy leads to learning/memory impairments in 3-panel runway and 3-lever operant tasks.

The effects of olfactory bulbectomy on the learning and memory of rats were examined, using several memory tasks. In reference memory and working memory tasks using a 3-panel runway apparatus, acquisition was delayed markedly by bilateral ablation of the olfactory bulb (OB). OB lesion performed after acquisition markedly impaired both reference and working memories. Even when the tasks were repeated for several sessions, the impairment of memory in OB-lesioned rats did not recover to the control level of the sham operation group. The delayed matching-to-lever location (DMLL) performance, which was examined using a 3-lever operant apparatus, was markedly impaired by OB lesions. This impairment was mild immediately after surgery, but tended to increase with time. Rats with OB-olfactory tubercule lesions show more severe impairment of memory in the DMLL performance. Reversal learning, using a 2-lever operant apparatus, was markedly impaired by OB lesions. The impairment of working and reference memories in OB lesioned rats, which was assessed using a 3-panel-runway apparatus, was reduced by cholinesterase inhibitor physostigmine and NIK-247. These findings suggest that the OB plays a very important role in the learning and memory processes necessary for both a working memory task and a reference memory task and that, at least in part, the memory impairment in OB lesioned rats is mediated by lowering of cholinergic function.

Animals↗

PubMed1993

Facilitatory effect of phorbol ester on 2-deoxyglucose uptake in rat hippocampal slices.

It is well known that synaptic potentiation in the hippocampus can be produced by phorbol ester, a protein kinase C activator. The 2-deoxyglucose uptake is an index of regional glucose utilization which predominantly reflects activity in the axonal terminal of neuronal pathways. In the present experiment, therefore, we examined whether application of phorbol ester produces a facilitatory effect on 2-deoxyglucose uptake by the rat hippocampus in vitro. The application of phorbol-12,13-dibutyrate (PdBU) produced an elevation of 2-deoxyglucose uptake, while pretreatment with PdBU for 60 min eliminated the pdBU-induced elevation. Pretreatment with protein kinase C inhibitors, K252a (0.1 and 1 microM) or staurosporine (0.1 and 1 microM), was found to block significantly the PdBU-induced elevation of 2-deoxyglucose uptake. In addition, the facilitatory effect of glutamate, quisqualate and carbachol on 2-deoxyglucose uptake was reduced by pretreatment with PdBU. In the present experiment, we demonstrated that application of phorbol ester caused an elevation of 2-deoxyglucose uptake, which is linked in turn to neuronal activity, suggesting a positive relationship between protein kinase C activation and energy consumption.

Alkaloids↗

PubMed1993

Improving effect of acetylcholine receptor agonists on a deficit of 2-deoxyglucose uptake in cerebral cortical and hippocampal slices in aged and AF64A-treated rats.

The aim of the present study was to determine whether the facilitation of 2-deoxyglucose (2-DG) uptake in the cerebral and hippocampal slices by nicotinic and muscarinic receptor agonists is compromised in the aged rat brain. For this, the effects of the nicotinic receptor agonist nicotine, the muscarinic receptor agonists oxotremorine and McN-A-343, and the ACh esterase inhibitors physostigmine and NK247 on 2-DG uptake in the brain slices of young (2-month-old) and aged (24-26-month-old) rats were tested. The decrements of 2-DG uptake in the cortical slices of aged rats were significantly attenuated by treatment with oxotremorine, nicotine and amiridine. In contrast, the metabolic responsivity of hippocampal slices to these drugs was reduced. To assess whether age-related changes in 2-DG uptake may be due to deficits in cholinergic function, we tested these drugs on the decrements of 2-DG uptake in ethylcholine aziridinium (a neurotoxic analog of choline) injected rats. The reductions of 2-DG uptake by injection of ethylcholine aziridinium was attenuated by oxotremorine but not by physostigmine. The present results reveal that metabolic decrements in the cerebral cortex from aged or ethylcholine aziridinium-injected rats were attenuated by muscarinic and nicotinic receptor agonists, suggesting that the muscarinic and nicotinic receptor mechanism in the cerebral cortex may be involved in cholinergic drug-induced functional recovery in aged rats.

Acetylcholine↗

PubMed1993

Ameliorative effects of the centrally active cholinesterase inhibitor, NIK-247, on impairment of working memory in rats.

Using a three-panel runway task, the effects of NIK-247 on impairment of working memory produced by scopolamine, hippocampal lesions, and cerebral ischemia were investigated in rats; these effects were compared with those of the well-known cholinesterase inhibitors, tetrahydroaminoacridine (THA) and physostigmine. Intraperitoneal injection of scopolamine (0.56 mg/kg) significantly increased the number of errors (pushes made on the two incorrect panels of the three-panel gates located at four choice points). NIK-247 (3.2-18 mg/kg PO), THA (1-10 mg/kg PO), and physostigmine (0.1 and 0.32 mg/kg IP) dose-dependently reduced the increase in errors induced by scopolamine. NIK-247 (32 mg/kg) was also effective in reducing the increase in errors produced by lesions of the dorsal hippocampus. A 5-min period of cerebral ischemia markedly increased the number of errors. NIK-247 (3.2 and 10 mg/kg), given immediately after blood flow recirculation and again 20 min before the runway test carried out 24 h after ischemia, significantly reduced the increase in errors expected to occur after ischemia. Tetrahydroaminoacridine (3.2 mg/kg) and physostigmine (0.1 mg/kg) similarly reversed the increased errors in ischemic rats. These results suggest that NIK-247 alleviates the impairment of working memory produced by scopolamine, hippocampal lesions, and cerebral ischemia, possibly through activation of the central cholinergic system.

Acetylcholinesterase↗

PubMed1993

Discriminative stimulus properties of NIK-247 and tetrahydroaminoacridine, centrally active cholinesterase inhibitors, in rats.

The discriminative stimulus effect of the novel centrally active cholinesterase inhibitor, NIK-247, was investigated in rats and compared with that of tetrahydroaminoacridine (THA). Rats were trained to discriminate either 10 mg/kg NIK-247 or 1.8 mg/kg THA from saline in a two-lever food-reinforced procedure. The stimulus effect of NIK-247 was substituted for by the cholinesterase inhibitors, THA and physostigmine. The THA stimulus was substituted for by NIK-247 and physostigmine. The muscarinic receptor agonist arecoline substituted for the NIK-247 and THA stimuli. Both stimulus effects of NIK-247 and THA were blocked by the muscarinic antagonist scopolamine. The dopaminergic-activating drugs amantadine and lisuride substituted for the stimulus effects of NIK-247 and THA. However, neither the NIK-247 nor the THA stimulus was antagonized by the dopamine antagonists haloperidol, SCH 23390, and sulpiride. These results suggest that the discriminative stimulus effects of NIK-247 and THA are mediated by muscarinic receptors, and that the dopaminergic activity resulting from cholinergic activation may account for some part of both stimuli.

Aminoquinolines↗

PubMed1993

Gastroprokinetic activity of nizatidine, a new H2-receptor antagonist, and its possible mechanism of action in dogs and rats.

We studied the anti-acetylcholinesterase (AChE) activity of a new H2-antagonist, nizatidine, in in vitro experiments and its gastroprokinetic action in the dog and rat in comparison with other H2-antagonists, neostigmine and cisapride. The IC50 of nizatidine for AChE was 6.7 x 10(-6) M, and this activity was reversible. The relative anti-AChE potency was in the following order: neostigmine > nizatidine > cimetidine >> famotidine. The inhibition of AChE by nizatidine was noncompetitive, with a Ki value of 7.4 x 10(-6) M. Gastrointestinal (GI) motility was examined during the interdigestive state in dogs with chronically implanted force transducers. Nizatidine (0.3-3 mg/kg, i.v.) significantly increased the motor index in a dose-dependent manner. It was of interest that the contractile response of the GI tract to nizatidine was similar to the interdigestive migrating contractions-like activity. At the doses used in this study, neither cimetidine nor famotidine had a significant effect on the motor index. Neostigmine at a higher dose of 0.06 mg/kg and cisapride at 0.3 mg/kg were found to stimulate GI contractions. Gastric emptying was determined in rats given phenol red as a liquid test meal. Nizatidine (3 mg/kg, i.p., or above) significantly increased gastric emptying, whereas the other H2-antagonists had no such effect. The ED50 and ED90 values of nizatidine for inhibition of gastric acid secretion were 0.18 and 3.22 mg/kg in dogs, and 2.94 and 19.6 mg/kg in rats, respectively. These findings suggest that nizatidine stimulates GI contractions and accelerates gastric emptying at gastric antisecretory doses.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1992

Ischemia-induced impairment of 2-deoxyglucose uptake and CA1 field potentials in rat hippocampal slices: protection by 5-HT1A receptor agonists and 5-HT2 receptor antagonists.

Various in vitro models have been developed to study ischemia and/or hypoxia. In the present experiment, we examined whether hypoxia/hypoglycemia (ischemia) in rat hippocampal slices reduced the 2-deoxyglucose (2-DG) uptake and CA1 field potentials evoked by stimulation of Schaffer collaterals. Autoradiograms revealed that ischemia for 15 or 20 min reduced 2-DG uptake in the stratum radiatum of the CA1 and the dentate gyrus. Similarly, the CA1 field potentials of slices exposed to ischemia for 15 and 20 min decreased by about 70 and 90% after a 6-h washout. In the second experiment, we evaluated the neuroprotective effect of the 5-HT1A receptor agonists 8-OH-DPAT and buspirone, and the 5-HT2 receptor antagonists cyproheptadine, mianserin and ketanserin on deficits of 2-DG uptake and Schaffer-CA1 field potentials induced by ischemia. The 5-HT1A receptor agonists and 5-HT2 receptor antagonists exhibited significant neuroprotective actions against ischemia-induced deficits. Therefore, impairments of 2-DG uptake and CA1 field potentials induced by ischemia may be good markers of ischemia-induced functional deficits. The attenuating action of 5-HT1A receptor agonists and 5-HT2 receptor antagonists were assessed using this model of ischemia.

Animals↗