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Biomedical subjects

Yuchuan Ding

Publications and source records attributed to Yuchuan Ding.

26 records · Page 2Linked to original sources

Regional brain cooling induced by vascular saline infusion into ischemic territory reduces brain inflammation in stroke.

The neuroprotective effect of hypothermia has long been recognized. Use of hypothermia for stroke therapy, which is currently being induced by whole body surface cooling, has been largely limited because of management problems and severe side effects (i.e., pneumonia). Our recent studies have demonstrated the significant therapeutic value of local brain cooling in the ischemic territory prior to reperfusion in stroke. The goal of this study was to determine if cerebral local cooling infusion could reduce stroke-mediated brain injury by inhibiting inflammatory responses. A hollow filament was used to block the middle cerebral artery (MCA) for 3 hours, and then to locally infuse the ischemic territory with 6 ml cold saline (20 degrees C) for 10 min prior to 48-h reperfusion. This cold saline infusion significantly ( P<0.01) reduced temperature of the MCA supplied territory (in cerebral cortex from 37.2+/-0.1 degrees C to 33.4+/-0.4 degrees C, in striatum from 37.5+/-0.2 degrees C to 33.9+/-0.4 degrees C), with the hypothermia remaining for at least 45 min after reperfusion. Consequently, significant ( P<0.01) reductions in endothelial expression of intracellular adhesion molecule-1 (ICAM-1), the key step for inflammatory progress, as well as leukocyte infiltration, were evident in both cortex and striatum after reperfusion. As a control, ischemic rats received the same amount of cold saline systemically through a femoral artery. A mild hypothermia was induced in the cerebral cortex (35.3+/-0.2 degrees C) but not in the striatum (36.8+/-0.2 degrees C). The reduced cortical temperature returned to normal within 5 min. Brain temperature in ischemic rats perfused locally with saline at 37 degrees C remained normal. Intensive expression of ICAM-1 and accumulation of leukocytes was observed in ischemic control groups without brain cooling infusion. In conclusion, brain hypothermia induced by local pre-reperfusion infusion ameliorated brain inflammation from stroke.

Analysis of Variance↗

Neurochemical comparison of synaptic arrangements of parvocellular, magnocellular, and koniocellular geniculate pathways in owl monkey (Aotus trivirgatus) visual cortex.

As in other primates, the lateral geniculate nucleus (LGN) of owl monkeys contains three anatomically and physiologically distinct relay cell classes, the magnocellular (M), parvocellular (P), and koniocellular (K) cells. M and P LGN cells send axons to the upper and lower tiers of layer IV, and K cells send axons to the cytochrome oxidase (CO) blobs of layer III and to layer I of primary visual cortex (V1). Our objective was to compare the synaptic arrangements made by these axon classes. M, P, and K axons were labeled in adult owl monkeys by means of injections of wheat germ agglutinin-horseradish peroxidase into the appropriate LGN layers. The neurochemical content of both pre- and postsynaptic profiles were identified by postembedding immunocytochemistry for gamma-aminobutyric acid (GABA) and glutamate. Our key finding is that the synaptic arrangements made by M, P, and K axons in owl monkey exhibit more similarities than differences. They are exclusively presynaptic, contain glutamate and form asymmetric synapses mainly with glutamate-positive dendritic spines. The majority of the remaining axons synapse with glutamatergic dendritic shafts. There are also differences between LGN pathways. M and P terminals are significantly larger and more likely to make multiple synapses than K axons, although M and P axons do not differ from each other in either of these characteristics. Of interest, a larger percentage of M and K axons than P axons make synapses with GABAergic dendritic shafts. Cells directly postsynaptic to M and K axons are known to exhibit orientation selectivity and, in some cases, direction selectivity. Cells postsynaptic to P axons do not show these properties, but instead tend to reflect their LGN inputs more faithfully; therefore, it is possible that these physiologic differences seen in the cortical cells postsynaptic to different LGN pathways reflect the differential involvement of inhibitory circuits.

Animals↗

Synaptic plasticity in thalamic nuclei enhanced by motor skill training in rat with transient middle cerebral artery occlusion.

The goal of this study was to determine if synaptic plasticity in the thalamus of rats subjected to stroke could be altered by motor training. Transient occlusion of right middle cerebral artery in adult female Sprague-Dawley rats (n = 35) was induced with an intraluminal filament followed by three training conditions, 1. motor skill training on Rota-rod requiring balance and coordination skills, 2. simple exercise on treadmill, and 3. nontrained controls. Synaptic plasticity in brain was evaluated by synapotophysin immunocytochemistry at 14 or 28 days after training procedures. Infarct volume was determined in Nissl stained sections. Both at 14 and 28 days after Rota-rod training, intense synaptophysin immunoreactivity was present in the right but not the left mediodorsal and ventromedial nuclei of thalamus of ischemic rats. In treadmill-trained animals, however, similarly intense synaptic plasticity in these two thalamic nuclei was seen only at 28 days. Immunostaining was found also in other brain regions adjacent to or remote from infarct site. The data suggest that motor training, particularly motor skill training involving balance and coordination, facilitates a uniquely lateralized synaptogenesis in the thalamus.

Animals↗

Impaired motor activity and motor learning function in rat with middle cerebral artery occlusion.

The poor quality of life after a stroke is largely attributed to deficits in cognitive-motor functioning. The goals of this study were to detect if damaged motor learning function were attributed to motor deficits in rats following a transient middle cerebral artery (MCA) occlusion. Stroke was induced by a 2-h occlusion of the MCA using an intraluminal filament. Motor functions were evaluated from 5 up to 28 days after reperfusion in ischemic and control rats. Motor function was detected by a series of motor tests (runway traversing and beam balancing, as well as foot fault placing, parallel bar crossing, rope and ladder climbing), and motor learning behavior was determined by analyzing the rate of improvement of impaired function during performance of the motor tasks. Significant (P<0.001) motor deficits were detected in the stroke group (n=10) while performing motor tasks that involve extensive coordination, in comparison to the controls (n=12). Although motor behavior was improved with repeated behavior testing, unparalleled rate of improvement of motor performance on rope and ladder climbing tests was found between the two groups, suggesting an impaired motor learning function. Brain tissue damage was detected in the ischemic animals 28 days after surgery, demonstrated by 40% infarct volume of contralateral hemisphere. Both motor learning and motor function were impaired in ischemic rats. The motor tests used in this study are sensitive, semi-quantitative, and reproducible measurements of functional impairment in rats following an ischemic stroke.

Animals↗

Cortical synaptic arrangements of the third visual pathway in three primate species: Macaca mulatta, Saimiri sciureus, and Aotus trivirgatus.

The koniocellular (K) pathway is one of three pathways from the lateral geniculate nucleus (LGN) to primate visual cortex (V1). K pathway projections to the cytochrome oxidase (CO) blobs of V1 suggest involvement in chromatic processing given reports that the CO blobs in diurnal primates contain cells selective for color. K LGN layers and CO blobs, however, are also well developed in nocturnal primates such as owl monkeys, which are likely to be color blind. Thus, the K pathway plays either different roles in different species or some as yet unidentified common role(s). Because synaptic arrangements underlie functional mechanisms, the purpose of this investigation was to compare the synaptic circuitry related to the K pathway within the CO blobs of two diurnal primates (macaque monkeys and squirrel monkeys) and one nocturnal primate (owl monkey). Presynaptic K axons were labeled with wheat germ agglutinin-HRP, and presynaptic and postsynaptic profiles in CO blobs were identified with post-embedding immunocytochemistry for GABA and glutamate. In all three species, K axon terminals are glutamatergic and larger than local axon terminals, suggesting that they have a greater impact on postsynaptic CO blob targets than signals arriving via layer IV from the P or M pathways. A greater proportion of K axons, however, synapse with larger glutamatergic shafts in the diurnal monkeys than in the nocturnal owl monkey, perhaps reflecting the importance of color within the K pathway of these diurnal species. Alternatively, the loss of color vision in the owl monkey could impact K pathway circuitry earlier in the pathway. The basic similarities between K axon circuitry within the CO blobs of the three primate species examined also could indicate that this pathway plays some common role or roles across species.

Animals↗

Prereperfusion saline infusion into ischemic territory reduces inflammatory injury after transient middle cerebral artery occlusion in rats.

BACKGROUND AND PURPOSE: In ischemic stroke, the ischemic crisis activates a cascade of events that are potentiated by reperfusion, eventually leading to cell death. The chief aim in this study was to investigate whether our new experimental model for stroke therapy, flushing the ischemic territory with saline before reperfusion, could minimize this damage by (1) reducing the inflammatory reaction and (2) improving regional microcirculation. METHODS: Stroke in Sprague-Dawley rats (n=39) was induced by a 2-hour middle cerebral artery occlusion with the use of a novel intraluminal hollow filament. Before 48-hour reperfusion, 20 of the ischemic rats received 7 mL isotonic saline at 23 degrees C or 37 degrees C infused into the ischemic area through the filament. Regional cerebral blood flow in cortex supplied by the right middle cerebral artery was measured by laser-Doppler flowmetry during ischemia and reperfusion. Leukocyte infiltration, microvascular plugging, and infarct volume were compared with the use of hematoxylin and eosin staining. Expression of intercellular adhesion molecule 1 (ICAM-1) was determined by immunocytochemistry. Neurological deficits were evaluated. RESULTS: After the prereperfusion infusion of saline, significantly (P<0.001) improved cerebral blood flow (105+/-12% of baseline) was obtained up to 48 hours after reperfusion, compared with 45+/-7% at 24 hours and 25+/-3% at 48 hours after reperfusion without local saline infusion. Significant (P<0.001) reductions in leukocyte infiltration (61%), vascular plugging (45%), infarct volume (approximately 65%), and neurological deficits were also produced. ICAM-1 expression in the infarct region was significantly (P<0.05) minimized by 37%. CONCLUSIONS: The reduced brain infarct and neurological deficits may be attributed to adequate reperfusion and ameliorated inflammation induced by local prereperfusion infusion.

Animals↗

Functional improvement after motor training is correlated with synaptic plasticity in rat thalamus.

The goals of this study were to determine whether functional outcome after motor training in rats was linked to synaptic plasticity in thalamus, and whether the Rota-rod apparatus, widely used to test motor function, could be used as an easy and quantitative motor skill training procedure. Adult female Sprague-Dawley rats (n = 39) were evaluated under three training conditions: 1. Movement requiring balance and coordination skills on Rota-rod; 2. simple exercise on treadmill; 3. nontrained controls. Motor function was evaluated by a series of motor tests (foot fault placing, parallel bar crossing, rope and ladder climbing) before and 14 or 28 days after training procedure. Synaptic strength in brain was assessed by synaptophysin immunocytochemistry. After 14 days of training, Rota-rod-trained animals significantly (p < 0.01) improved motor performance, compared to treadmill and nontrained animals. Animals with up to 28 days of simple exercises on the treadmill did not show a significantly improved performance on most motor tasks, except for an improvement in foot fault placing. Intensive synaptophysin immunoreactivity was present in the right but not the left mediodorsal and ventromedial nuclei of thalamus in Rota-rod-trained rats at 14 and 28 days, and in treadmill-trained rats at 28 days. The data suggested that functional outcome is effectively improved by motor skill training rather than by simple exercises, and this may be related, at least partially, to uniquely lateralized synaptogenesis in the thalamus. Both Rota-rod and treadmill could be quantitatively used in rats for motor training of different complexity.

Animals↗

Prereperfusion flushing of ischemic territory: a therapeutic study in which histological and behavioral assessments were used to measure ischemia-reperfusion injury in rats with stroke.

OBJECT: In ischemic stroke, the ischemic crisis activates a cascade of traumatic events that are potentiated by reperfusion and eventually lead to neuronal degeneration. The primary aim of this study was to investigate a procedure that could minimize this damage by interfering with the interactions between reestablished blood flow and ischemically damaged tissue, as well as by improving regional microcirculation. METHODS: Using a novel hollow filament, the authors flushed the ischemic territory with heparinized saline before vascular reperfusion after occlusion of the middle cerebral artery (MCA). The results demonstrate a statistically significant (p < 0.001) reduction in infarct volume (75%; from 45.3 +/- 3.6% to 11.4 +/- 1.7%, determined with Nissl staining) in rats in which a 2-hour MCA occlusion was followed by a 48-hour reperfusion. Infarction and neuronal degeneration were confirmed using silver staining, which revealed a significantly larger infarct (36.3%, p < 0.05) than that detected with Nissl staining. The long-term neuroprotection of the prereperfusion flushing was also evaluated. This was determined by a series of motor behavior tasks (foot placing, parallel bar traversing, rope and ladder climbing) performed up to 28 days after reperfusion. Motor deficits were found to be significantly ameliorated in animals that underwent the flushing procedure (p < 0.001). In addition, neurological outcome was also improved significantly (p < 0.001) in the same animals. CONCLUSIONS: These results indicate that interaction between reperfusion and the metabolically and biochemically compromised tissue could be interrupted by the prereperfusion flushing procedure, which could lead to a reduction in brain injury from stroke. Mechanical reopening of the cerebral occlusion with local flushing and isolated reperfusion of the regionally injured brain might offer new treatment options for patients with stroke.

Animals↗