Global Ischemia In Rats Research Articles

Deep prepiriform cortex modulates neuronal cell death in global ischemia.

Deep prepiriform cortex has an important role in modulating neurotransmission during limbic seizures. We used pharmacologic blockade of non-N-methyl-D-aspartate (NMDA) receptors to study excitatory circuitry from the deep prepiriform cortex to the hippocampus during global ischemia in rat. NBQX, a potent non-NMDA glutamate receptor antagonist, was microinjected stereotactically into the deep prepiriform cortex before global ischemia for 10 min. Neuronal cell death in the hippocampus was evaluated quantitatively 72 h after ischemia. The NBQX-injected rats had a greater number of surviving cells in CA1 sector of hippocampus than did saline-injected controls or rats that received NBQX injections 1 mm from the target. Thus, excitatory amino acid-mediated circuitry emanating from deep prepiriform cortex modulates ischemic neuronal injury in the hippocampus.

Effects of alpha 2-adrenoceptor antagonists and imidazoline2-receptor ligands on neuronal damage in global ischaemia in the rat.

1. In the present study the neuroprotective effects of 3 mg/kg idazoxan, an alpha 2-adrenoceptor antagonist and imidazoline2-receptor (I2-receptor) ligand, 3 mg/kg methoxyidazoxan, a specific alpha 2-adrenoceptor antagonist, and 0.6 and 3 mg/kg BU224, a selective I2-receptor ligand, were evaluated following 10 min of global ischaemia in rats. 2. Neuronal cell counts in the CA1 region of the hippocampus 8 days postischaemia indicated 46-96% cell loss compared with control (P < 0.001) and a 320% increase in [3H]-PK11195 binding (P < 0.001) used as a marker of gliosis. No significant neuroprotective effect could be detected on these markers of neuronal damage in the active treatment groups. In a subset of idazoxan-treated rats, neuronal loss and gliosis was minimal. 3. Mean body temperature over 3 h postischaemia was lower in idazoxan-treated rats than in the other treatment groups (P < 0.001) and there was a correlation between mean body temperature and cell counts (P < 0.01) and mean body temperature and gliosis in this group (P = 0.057). 4. These results indicate that at the doses used neither BU224 nor methoxyidazoxan are neuroprotective in this ischaemia model and they raise the possibility that any neuroprotective effect of idazoxan may be related to hypothermic effects of the drug.

O-279 - Expression of cytokine-induced neutrophil chemoattractant-1 (CINC-1) and IL-6 following a transient global ischemia in rats

O-279 - Expression of cytokine-induced neutrophil chemoattractant-1 (CINC-1) and IL-6 following a transient global ischemia in rats

Dextromethorphan reduces functional deficits and neuronal damage after global ischemia in rats

Glutamate antagonists have been shown to be neuroprotective in animal models of cerebral ischemia. Global cerebral ischemia in rats leads to selective neuronal damage in the hippocampus and striatum. Following ischemia a transient locomotor hyperactivity and a deficit in spatial learning and memory occurs. The aim of the present study was to investigate the potential neuroprotective effect of dextromethorphan, an antagonist at the N-methyl- d-aspartate receptor, with behavioural and histological measures of global ischemia in rats. Global ischemia was induced by four-vessel occlusion (4VO) for 20 min in rats. Dextromethorphan was administered 20 min before induction of ischemia at a dose of 10 or 50 mg/kg. Before and on day 1, 3 and 5 after operation the spontaneous locomotor activity was measured. One week after surgery spatial learning was tested in the Morris water maze. After behavioural testing the animals were sacrificed and the neuronal damage was assessed. Treatment with 50 mg/kg of dextromethorphan reduced the increase in locomotor activity observed on day 1 and 3 after ischemia. In the water maze dextromethorphan reduced the increase in escape latency and in swim distance induced by 4VO. Furthermore, the ischemia-induced reduction in time spent in the quadrant of the former platform position during the probe trial was increased by treatment with dextromethorphan. Neuronal damage in the CA1 sector of the hippocampus and in the dorsolateral striatum produced by 4VO was significantly attenuated by dextromethorphan. The present results demonstrate that protective effects on neuronal damage may be related to an attenuation of deficits in spatial leaning and memroy following global ischemia.

TGF-beta 1 protects hippocampal neurons against degeneration caused by transient global ischemia. Dose-response relationship and potential neuroprotective mechanisms.

Transforming growth factor-beta 1 (TGF-beta 1) has been shown to rescue cultured neurons from excitotoxic and hypoxic cell death and to reduce infarct size after focal cerebral ischemia in mice and rabbits. The present study investigated the effects of TGF-beta 1 in a different pathophysiological setting and the delayed neuronal death of hippocampal pyramidal cells after transient global ischemia in rats, and evaluated the potential mechanisms of the neuroprotective activity of TGF-beta 1. Transient forebrain ischemia was induced in male adult Wistar rats with bilateral occlusion of both common carotid arteries combined with systemic hypotension for 10 minutes. Seven days after ischemia, brains were perfusion-fixed and stained for histological evaluation. TGF-beta 1 or vehicle was injected intracerebroventricularly (ICV; 0.5, 4, and 50 ng) or intrahippocampally (4 ng) 1 hour before ischemia. For in vitro studies, hippocampal neurons were derived from E17 rat embryos and cultured for 10 to 14 days. Cells were exposed to (1) S-nitrosocysteine (SNOC; 30 mumol/L) to induce nitric oxide-induced oxidative injury and (2) staurosporine (0.03 mumol/L) to induce apoptotic cell death. Transient forebrain ischemia caused extensive degeneration of CA1 hippocampal pyramidal cells in vehicle-treated control animals. Ischemic injury was not significantly reduced after ICV administration of 0.5 ng TGF-beta 1 (71 +/- 7% damaged neurons versus 84 +/- 3% in vehicle-treated controls: n = 9 and 11, respectively; P = .07, Mann-Whitney U test). Administration of 4 ng TGF-beta 1 reduced the percentage of damaged CA1 pyramidal cells from 71 +/- 10% in controls to 52 +/- 7% in TGF-beta 1-treated animals (n = 11 and 12, respectively; P = .04). TGF-beta 1 (4 ng) also produced significant protection when injected directly into the hippocampal tissue. In contrast, ICV administration of 50 ng TGF-beta 1 failed to show a protective effect in two separate sets of experiments. In vitro, a 24-hour pretreatment of the cultured hippocampal neurons with TGF-beta 1 (0.1 to 10 ng/mL) significantly inhibited both nitric oxide and staurosporine neurotoxicity. Posttreatment with TGF-beta 1 (10 ng/mL) also inhibited staurosporine neurotoxicity but actually potentiated nitric oxide-induced neuronal injury. We demonstrated that TGF-beta 1 in a surprisingly low dose range has the capacity to reduce injury to CA1 hippocampal neurons caused by transient global ischemia in rats. This protective action could well be associated with the antioxidative and antiapoptotic effects of TGF-beta 1 demonstrated in vitro.

Pretreatment but not posttreatment with GYKI 52466 reduces functional deficits and neuronal damage after global ischemia in rats

Glutamate antagonists have been shown to be neuroprotective in animal models of cerebral ischemia. Global cerebral ischemia in rats leads to selective neuronal damage in the hippocampus and striatum. Following ischemia a deficit in spatial learning and memory occurs. The aim of the present study was to investigate the potential neuroprotective effect of GYKI 52466, an antagonist at the non- N-methyl- d-aspartate receptor, with behavioural and histological measures of global ischemia in rats. Global ischemia was induced by four-vessel-occlusion (4VO) for 20 min in rats. GYKI 52466 (30 mg/kg i.p.) was administered either 20 min before induction of ischemia or immediately after onset of reperfusion. One week after surgery spatial learning was tested in the Morris water maze. After behavioural testing the animals were sacrificed and the neuronal damaged was assessed. GYKI 52466 reduced the increase in escape latency and in swim distance induced by 4VO when given before ischemia but not when applied after ischemia. Neuronal damage in the CA1 sector of the hippocampus produced by 4VO was significantly attenuated by pretreatment but not by posttreatment with GYKI 52466. Striatal neuronal damage was not affected by either treatment with GYKI 52466. GYKI 52466 had neuroprotective effects in a rat model of global cerebral ischemia. Pretreatment with GYKI 52466 protected rats against behavioural deficits and hippocampal neuronal damage induced by 4VO.

Pretreatment but not posttreatment with GYKI 52466 reduces functional deficits and neuronal damage after global ischemia in rats

Glutamate antagonists have been shown to be neuroprotective in animal models of cerebral ischemia. Global cerebral ischemia in rats leads to selective neuronal damage in the hippocampus and striatum. Following ischemia a deficit in spatial learning and memory occurs. The aim of the present study was to investigate the potential neuroprotective effect of GYKI 52466, an antagonist at the non-N-methyl-d-aspartate receptor, with behavioural and histological measures of global ischemia in rats. Global ischemia was induced by four-vessel-occlusion (4VO) for 20 min in rats. GYKI 52466 (30 mg/kg i.p.) was administered either 20 min before induction of ischemia or immediately after onset of reperfusion. One week after surgery spatial learning was tested in the Morris water maze. After behavioural testing the animals were sacrificed and the neuronal damaged was assessed. GYKI 52466 reduced the increase in escape latency and in swim distance induced by 4VO when given before ischemia but not when applied after ischemia. Neuronal damage in the CA1 sector of the hippocampus produced by 4VO was significantly attenuated by pretreatment but not by posttreatment with GYKI 52466. Striatal neuronal damage was not affected by either treatment with GYKI 52466. GYKI 52466 had neuroprotective effects in a rat model of global cerebral ischemia. Pretreatment with GYKI 52466 protected rats against behavioural deficits and hippocampal neuronal damage induced by 4VO.

Memantine reduces functional and morphological consequences induced by global ischemia in rats

In this study the effect of memantine, an antagonist at the N-methyl- d-aspartate receptor, on spatial learning deficit and on neuronal damage following transient: cerebral ischemia was evaluated. Global ischemia was induced by four-vessel-occlusion (4VO) for 20 min in rats. Memantine was administered 20 min before induction of ischemia at a dose of 10 or 20 mg/kg. One week after surgery spatial learning was tested in the Morris water maze. Treatment with the higher dose of memantine reduced the increase in escape latency and in swim distance induced by 4VO. Neuronal damage in the CA1 sector of the hippocampus and in the striatum produced by 4VO was significantly attenuated by 20 mg/kg memantine. Treatment with the lower dose of memantine bad no influence on the deficit in spatial learning and the neuronal damage resulting from ischemia. The present data demonstrate that treatment with a neuroprotective agent like memantine can reduce functional as well as morphological sequelae induced by ischemia.

Ischemic brain damage and memory impairment: a commentary.

Studies in humans and monkeys have identified structures in the medial temporal lobe essential for memory (the hippocampal region, i.e., the dentate gyrus, the hippocampus, and the subicular complex, and the adjacent perirhinal, entorhinal, and parahippocampal cortices). Additional work has revealed that for both species, damage limited to the hippocampal region produces less severe memory impairment than damage that includes additional structures within the medial temporal lobe. This work has been based on both neurosurgical lesions and on lesions produced by global ischemia or anoxia. An important issue about ischemic damage is whether the damage identifiable in histopathological examination provides an accurate estimate of direct neural damage or whether additional direct damage might be present that is sufficient to disrupt neuronal function in areas important for memory and sufficient to impair behavioral performance, but not sufficient to progress to cell death and to be detectable in conventional histopathology. This commentary explores the issue of ischemic damage and memory impairment. Although few studies have addressed this issue directly, the currently available data from global ischemia in rats, monkeys, and humans are consistent with the hypothesis that the detectable neuronal damage is responsible for the severity of the observed behavioral impairment. Yet it is also true that this hypothesis has not been the target of very much systematic work. We encourage additional experimental work, especially in rats, that could further illuminate how to evaluate the behavioral effects of ischemic lesions.

Effects of Cerebrolysin on cytoskeletal proteins after focal ischemia in rats.

In previous studies it was shown that Cerebrolysin® has cerebroprotective effects after moderate global ischemia in rats. In order to investigate mechanisms of these effects, we studied the influence of Cerebrolysin® on dynamics of neurodegeneration of cytoskeletal proteins (MAP2 and alpha-tubulin) after focal brain ischemia in adult male Thomae rats. We used different combinations of ischemia/reperfusion-intervals (2 hrs/90 min and 3 hrs/15 min). Ischemia was induced by a reversible occlusion of the middle cerebral artery by insertion of a nylon monofilament thread. Spreading depressions, ischemic depolarisation, and ECoG were recorded above the core and penumbra of the infarct. CBF (cortical blood flow) was measured in the same regions by a two channel Laser Doppler flowmeter. After fixation procedure and paraffin embedding, the brains were sectioned in 24 slices, each 0.5 mm thick. Slices (5µm) from each plane were used for immunohistochemical staining against MAP2 and alpha-tubulin. The size of the infarction zone and the penumbra was calculated morphometrically. First results indicate that Cerebrolysin® may stabilize cytoskeletal structures. More details will be presented.KeywordsPublic HealthImmunohistochemical StainingMiddle Cerebral ArteryBrain IschemiaFederal RepublicThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Combined postischemic hypothermia and delayed MK-801 treatment attenuates neurobehavioral deficits associated with transient global ischemia in rats

The present study was designed to determine whether postischemic hypothermia, delayed MK-801 (dizocilpine) administration, or a combination of these treatments can provide lasting neurobehavioral protection following transient global ischemia in rats. Rats were subjected to 10 min of normothermic (37°C) ischemia induced by 2-vessel occlusion and hypotension (50 mmHg) or sham procedures. Ischemia was followed by either: (a) 3 h at normothermic brain temperatures, (b) 3 h of postischemic brain hypothermia at 30°C, (c) hypothermia coupled with MK-801 (4 mg/kg, i.p.) on postischemic days 3, 5 and 7, or (d) postischemic MK-801 treatment alone. Neurobehavioral evaluation 6–8 weeks following surgery showed that normothermic ischemia (NI) was associated with water maze navigational deficits, including performance on a simple place task involving finding a hidden platform maintained in one position for 6 days, and a learning set task in which the platform was moved to a different location each day (both P's< 0.02 vs. sham). NI was also associated with increased locomotion in an open field ( P < 0.01 vs. sham). A combination of postischemic hypothermia and delayed MK-801 injections provided partial protection from ischemic-associated hyperactivity in the open field ( P < 0.02 vs. NI), and robust protection from simple place task deficits ( P < 0.02 vs. NI). Evidence for significant protective effects of MK-801 or hypothermia alone was observed in the learning set, during the final trial blocks each day. These results provide further evidence for neuroprotective effects of these treatments at chronic survival intervals, and indicate that the therapeutic window for attenuating ischemic damage is considerably longer than has heretofore been appreciated.

Dynamic monitoring of cerebral metabolites during and after transient global ischemia in rats by quantitative proton NMR spectroscopy in vivo

Localized proton NMR spectroscopy was used to dynamically monitor alterations of cerebral metabolites before, during, and after a 10 min period of global forebrain ischemia in anesthetized rats. Metabolic assessment was based on user-independent determination of absolute brain concentrations at a nominal temporal resolution of 1.6 min. While the concentrations of N-acetyl aspartate (neuronal marker), creatines, cholines, and myo-inositol (glial marker) remained constant, ischemia induced a rapid decline of brain glucose. One hour after reperfusion, glucose recovered to 4.1 +/- 2.2 mmol/kg wet weight significantly above the basal value of 2.3 +/- 1.3 mmol/kg wet weight. Mirroring glucose depletion, lactate increased from 1.0 +/- 0.6 to 13.5 +/- 1.5 mmol/kg wet weight 10-15 min after the onset of ischemia. During reperfusion lactate clearance was characterized by a first-order rate constant of 0.03/min. The time courses of glucose and lactate reflect the rapid onset of anaerobic glycolysis during states of critically diminished blood flow. Assuming complete ischemia the production of lactate from glucose and cerebral glycogen stores yields a brain glycogen concentration of 4.7 +/- 0.9 mmol glycosyl unit/kg wet weight. Elevation of brain glucose during early reperfusion suggests a transient mismatch of glucose uptake and consumption during the first 1-2 hours post ischemia.

Amino acid transport after transient global ischemia in rats: Quantitative autoradiographic study using 3-[ 125I]iodo-alpha-methyl- l-tyrosine

We studied the influence of reperfusion on amino acid transport of the brain after transient global ischemia in rats. The animals were subjected to 30-min four-vessel occlusion according to the procedures developed by Pulsinelli prior to recirculation for 3, 6, 24, 48 and 72 h. We used 3-[ 125I]iodo-alpha-methyl- l-tyrosine as an autoradiographic tracer for selective cerebral amino acid transport maker. Following 30-min global ischemia, uptakes of 3-[ 125I]iodo-alpha-methyl- l-tyrosine were significantly (P < 0.05) lower in substantia nigra, striatum and ventral tegmental area (6, 24, 48 and 72 h post-reperfusion), but significantly (P < 0.05) higher in cortex and thalamus (3 and 6 h post-reperfusion). The influence of transient global ischemia on cerebral amino acid transport manifested region-specific three different patterns; namely, suppression, acceleration and no change in amino acid transport. The influence of transient ischemia on catecholamine-synthesizing brain sites is most remarkable.

Neuroprotective effects of Ginkgo biloba constituents

The neuroprotective effects of Ginkgo biloba extract (EGb 761) and some of its constituents were tested by using the mouse and the rat model of focal cerebral ischemia, the rat model of global cerebral ischemia and primary cultures of neurons obtained from newborn rat hippocampi and chick embryo telencephalic hemispheres. In the models of focal ischemia, 2 days after occlusion of the middle cerebral artery the infarct area on the mouse brain surface and the infarct volume of the rat brain were measured. The infarct area on the mouse brain was dose-dependently (5–20 mg/kg, s.c.) reduced by bilobalide administered 60 min before ischemia. When administered immediately after ischemia, 10 mg/kg bilobalide also diminished the infarct area. The same dose of bilobalide administered to rats 60 min before occluding the middle cerebral artery reduced the cortical and the total infarct volume significantly. Ginkgolide A (50 mg/kg, s.c.) and ginkgolide B (100 mg/kg, s.c.) also had cerebroprotective effects in the mouse model of focal cerebral ischemia, but ginkgolides C and J did not. EGb 761 (2 × 100 mg/kg,i.v.) increased the cerebral blood flow after 10 min of global ischemia in rats but neuroprotection was not demonstrable. Ginkgolide B (1 μM) and bilobalide (10 μM) were shown to protect cultured rat hippocampal neurons against damage caused by glutamate. Bilobalide (0.1 μM) also enhanced the percentage of viable neurons in primary cultures from chick embryo hemispheres when damaged with 1 mM cyanide. The results demonstrate different types of neuroprotective and cerebrovascular effects of the Ginkgo biloba extract and some of its constituents.

Posttreatment with EPC-K1, an inhibitor of lipid peroxidation and of phospholipase A2 activity, reduces functional deficits after global ischemia in rats

In this study the effect of an inhibitor of lipid peroxidation and of phospholipase A2 activity, EPC-K1, on spatial learning deficit and neuronal damage following transient cerebral ischemia was evaluated. Global ischemia was induced by four-vessel occlusion (4VO) for 20 min in rats. EPC-K1 (10 mg/kg IP) was administered either a) 15 min before induction of ischemia, b) immediately after, or c) 30 min after onset of repertusion. One week after surgery spatial learning was tested in the Morris water maze. EPC-K1 reduced the deficit in spatial learning when given immediately or 30 min after the onset of reperfusion but not when applied 15 min before ischemia. Neuronal damage in the CA1 sector of the hippocampus produced by 4VO was slightly, but not significantly attenuated by posttreatment. The present data demonstrate that posttreatment with EPC-K1 exerts a protective effect on deficits in spatial learning induced by 4VO. These results support the hypothesis that lipid peroxidation and activation of phospholipase A2 contribute to functional alterations of the brain during reperfusion following forebrain ischemia.

Cortical hypoperfusion after global forebrain ischemia in rats is not caused by microvascular leukocyte plugging.

We tested the hypothesis that cerebral hypoperfusion after experimental global cerebral ischemia is caused by plugging of the microcirculation with activated leukocytes using in vivo microscopic observation of the behavior of leukocytes in the cortical microcirculation during the transition from postischemic hyperperfusion to hypoperfusion. Anesthetized and ventilated rats (n = 24) were equipped with a closed cranial window. Physiological variables and cortical regional cerebral blood flow (laser-Doppler flowmetry) were measured continuously. Leukocytes were labeled intravitally with rhodamine 6G and visualized in the microcirculation of the brain surface and outer layers of the cortex with confocal laser scanning microscopy from preischemia to 4 hours after reperfusion that followed 10 minutes of global cerebral ischemia (rCBF < 10% of control). In controls (n = 8), there were no signs of leukocyte activation over the 4-hour observation period. In ischemic rats (n = 16), during the transition from hyperperfusion to hypoperfusion there was no change in the behavior of leukocytes. Most notably, no capillary pluggers were seen. In the postischemic period only a slight increase of the number of leukocytes rolling along or sticking to the venular endothelium was seen, and very few capillaries were plugged by leukocytes. Extravasation of leukocytes into the brain tissue was observed in 8 rats beginning 2 hours after ischemia with a variable degree between animals. Because there was only mild activation of leukocyte-endothelium interaction within the first hours of reperfusion after 10 minutes of global forebrain ischemia, because no leukocytes plugged superficial cortical capillaries during the transition from hyperperfusion to hypoperfusion, and because the regional cerebral blood flow transition was very rapid, we speculate that leukocyte plugging is not responsible for the early cortical hypoperfusion seen after brief global ischemia in rats.

NMDA and non-NMDA receptor gene expression following global brain ischemia in rats: effect of NMDA and non-NMDA receptor antagonists.

Transient forebrain or global ischemia in rats induces selective and delayed damage of hippocampal CA1 neurons. In a previous study, we have shown that expression of GluR2, the kainate/alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor subunit that governs Ca2+ permeability, is preferentially reduced in CA1 at a time point preceding neuronal degeneration. Postischemic administration of the selective AMPA receptor antagonist, 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo(f)quinoxaline (NBQX), protects CA1 neurons against delayed death. In this study we examined the effects of NBQX (at a neuroprotective dose) and of MK-801 (a selective NMDA receptor antagonist, not protective in this model) on kainate/AMPA receptor gene expression changes after global ischemia. We also examined the effects of transient forebrain ischemia on expression of the NMDA receptor subunit NMDAR1. In ischemic rats treated with saline, GluR2 and GluR3 mRNAs were markedly reduced in CA1 but were unchanged in CA3 or dentate gyrus. GluR1 and NMDAR1 mRNAs were not significantly changed in any region examined. Administration of NBQX or MK-801 did not alter the ischemia-induced changes in kainate/AMPA receptor gene expression. These findings suggest that NBQX affords neuroprotection by a direct blockade of kainate/AMPA receptors, rather than by a modification of GluR2 expression changes.

Neuronal protective effects of calcium antagonists in cerebral ischemia

We investigated the effects of calcium antagonists against ischemic injury in vivo and against excitotoxic damage in vitro. In vivo nimodipine protected significantly the CA1 hippocampal neurons from neurodegeneration after transient global ischemia in rats without changing the local cerebral blood flow. Furnidipine reduced the area of ischemia after permanent MCA-occlusion in mice. The results in vitro using the Ca 2+-sensitive dye fura-2 showed that nimodipine reduced in a dose-dependent manner the elevation of [Ca 2+] i in hippocampal neurons induced by K +-stimulation. The present in vitro and in vivo data show that calcium antagonists are potent agents in protecting neurons against the deleterious consequences of an excitotoxic or ischemic insult.

A new approach to the integrity of dual blood-brain barrier functions of global ischemic rats. Barrier and carrier functions.

We studied the influence of reperfusion on carrier and barrier functions of the blood-brain barrier after transient global ischemia in rats. We used iodine-125-labeled 3-iodo-alpha-methyl-L-tyrosine and carbon-14-labeled sucrose as tracers for studying carrier and barrier functions of the blood-brain barrier, respectively. Brain uptakes of these two tracers were measured in Wistar rats subjected to either 15- or 30-minute four-vessel occlusion developed by Pulsinelli and Brierly before recirculation for 3, 6, 24, 48, and 72 hours. Tracer (5 microCi) was injected intravenously in each rat 30 minutes before killing the animal. Following 15- or 30-minute ischemia, [14C]sucrose uptakes were significantly higher at 3 and 6 hours of reperfusion before recovery to control values after reperfusing for 24 to 48 hours in almost all brain regions. However, a rebound in radioligand uptake was significantly manifested in some sites at 72 hours after reperfusion (p < 0.05 to p < 0.01). Uptakes of 125I-3-iodo-alpha-methyl-L-tyrosine were brain site-dependent: significantly (p < 0.05) higher in cortex (3 and 48 hours after reperfusion) and thalamus (3, 6, and 48 hours after reperfusion) but significantly (p < 0.05 to p < 0.01) lower in striatum, cortex (72 hours after reperfusion), and midbrain (6, 24, and 72 hours after reperfusion). Because the [14C]sucrose uptake in brain was 10% lower than that of 125I-3-iodo-alpha-methyl-L-tyrosine, the change in absolute transport of the latter tracer was approximated to its brain uptake. The carrier and barrier functions of the blood-brain barrier should be evaluated separately. The radioligand 125I-3-iodo-alpha-methyl-L-tyrosine may serve as a useful tool to evaluate the carrier function of the blood-brain barrier after transient cerebral ischemia in rats.

Switch in glutamate receptor subunit gene expression in CA1 subfield of hippocampus following global ischemia in rats

Switch in glutamate receptor subunit gene expression in CA1 subfield of hippocampus following global ischemia in rats