MCAO Group Research Articles

Abstract WP110: TLR5 Is Related To Neuroprotective Mechanism Of Postconditioning Through NF-κB-Akt Survival Pathway In Cerebral Ischemia

Background and Purpose: Although postconditioning following stroke has indicated neuroprotective mechanisms, little is known about the mechanisms that lead to neuroprotection. Using flagellin, NF-kB activators and agonists of TLR5, we tested whether TLR5 plays an integral role in NF-kB activation and postconditioning-induced neuroprotection. Method: For the postconditioning group, 30 min of MCAO was induced, then 5 min of reperfusion was performed, after which the MCA was again occluded for 5 min. Using an anaerobic chamber, bEnd.3 and BV-2 cells in the postconditioning group were subjected to 180 min OGD (oxygen and glucose deprivation) and were allowed to recover for 10 min before being subjected to 10 more min of OGD. The control group was subjected to 180 min of OGD. Flagellin, an agonist of TLR5, was used to clarify the association between TLR5 and postconditioning in vivo (ICV; 50, 100 ng/mouse) and in vitro (0.1, 0.25, 0.5, 1 ng/ ml) experiments. Immunoprecipitation and immunoblotting were used to determine the interactions of TLR5, MyD88, p-Akt, and NF-κB. Results: Animals treated with postconditioning showed significant differences in infarct volumes compared with the MCAO group up to 60.51%. Postconditioning elevated NF-κB translocation to the nuclei (p<0.001) as early as 1 hour after postconditioning following tFCI and OGD. The protein interactions and expressions of TLR5, MyD88 and p-Akt (p<0.05) were increased in in vivo and in vitro postconditioning. Additionally, inhibition of Akt phosphorylation by Akt inhibitor IV decreased NF-κB translocation after postconditioning. To clarify the role of NF-κB in postconditioning, flagellin was used as a postconditioning mimicking agent. The treatment of flagellin reduced hypoxic-ischemic injury and increased nuclear accumulation of NF-κB and activation of Akt up to 4 hr. Conclusions: Postconditioning has neuroprotective effects by activating NF-κB and Akt survival pathway under TLR5 after stroke. Agonist of TLR5, flagellin simulated NF-κB and Akt survival pathways in cerebral ischemia. Our results suggested new mechanisms of postconditioning through TLR-5 and NF-κB, which leads to the possibility of development of a postconditioning mimicking agent using NF-κB activators such as flagellin.

The protection by Octreotide against experimental ischemic stroke: Up-regulated transcription factor Nrf2, HO-1 and down-regulated NF-κB expression

BackgroundInflammatory and oxidative damage play a pivotal role in cerebral ischemic pathogenesis and may represent a therapeutic target. Octreotide (OCT) has been proved to elicit a variety of biological effects through its anti-inflammatory and anti-oxidant properties in the treatment of severe acute pancreatitis and ischemia-reperfusion injury in retina and intestine. However little is known regarding the effect of OCT in ischemic stroke. Here, we designed this study to investigate the protective effect of OCT in ischemic stroke and explore the potential underlying mechanisms. Methods: Male Sprague-Dawley rats were subjected to permanent middle cerebral artery occlusion (pMCAO) and randomly divided into four groups: Sham (sham-operated), MCAO (pMCAO+0.9% saline), OCT-L (pMCAO+OCT 50μg/kg) and OCT-H (pMCAO+OCT 100μg/kg) groups. OCT was administered intraperitoneally immediately after stroke. Neurological deficit scores, infarct volume and brain water content were measured at 24h after stroke. Immunohistochemical staining and western blot were used to analyze the expressions of Nrf2, HO-1 and NF-κB. SOD and MDA were measured by spectrophotometer. Results: Compared with MCAO group, OCT significantly alleviated neurological deficit, lessened infarct volume and brain edema (P<0.05), upregulated the expression of Nrf2, HO-1 and SOD (P<0.05), and decreased the expression of NF-κB and MDA (P<0.05). Conclusions: OCT protected the brain against cerebral ischemic damage; this effect may be through upregulation of transcription factor Nrf2, HO-1 and downregulation of NF-κB expression.

Protective Effect of Luteolin in Experimental Ischemic Stroke: Upregulated SOD1, CAT, Bcl-2 and Claudin-5, Down-Regulated MDA and Bax Expression

Luteolin recently has been proved to elicit a vanity of biological effects through its antioxidant and anti-apoptosis properties. Oxidative and apoptosis damage play an important role in cerebral ischemic pathogenesis and may represent a target for treatment. The aim of this study was to evaluate the neuroprotective effects of luteolin and the underlying mechanisms in cerebral ischemia. Focal cerebral ischemia was induced in adult male Sprague-Dawley rats by permanent middle cerebral artery occlusion (pMCAO). Luteolin was injected intraperitoneally at different doses of 10 or 25mg/kg immediately after pMCAO. Experiment 1, luteolin's neuroprotective effect was analyzed. Neurological deficits, brain water content and infarct volume were evaluated at 24 and 72h after pMCAO. SOD1, Bcl-2, and Bax expression were measured by immunohistochemistry, western blot and reverse transcription-polymerase chain reaction. Experiment 2, luteolin's anti-oxidative activities were evaluated. SOD1, CAT activities, and MDA content were measured by spectrophotometer. Experiment 3, the influence of luteolin on claudin-5 was detected. Compared with MCAO group, luteolin significantly increased the activities of SOD1, CAT, Bcl-2 and claudin-5 (P<0.05), decreased the levels of MDA and Bax (P<0.05), and alleviated the neurological deficits, infarct volume and brain water content (P<0.05). The results indicated that luteolin protected the brain from ischemic damage, and this effect may be through reduction of oxidative stress and apoptosis, and upregulation of the expressions of claudin-5.

Spatiotemporal Characteristics of Postischemic Hyperperfusion with Respect to Changes in T1, T2, Diffusion, Angiography, and Blood–Brain Barrier Permeability

The spatiotemporal dynamics of postischemic hyperperfusion (HP) remains incompletely understood. Diffusion, perfusion, T2, T1, angiographic, dynamic susceptibility-contrast magnetic resonance imaging (MRI) and magnetic resonance angiography were acquired longitudinally at multiple time points up to 7 days after stroke in rats subjected to 30-, 60-, and 90-minutes middle cerebral artery occlusion (MCAO). The spatiotemporal dynamics of postischemic HP was analyzed and compared with T1, T2 and blood-brain barrier (BBB) changes. No early HP within 3 hours after recanalization was observed. Late (12 hours) HP was present in all animals of the 30-minute MCAO group (N=20), half of the animals in the 60-minute MCAO group (N=8), and absent in the 90-minute MCAO group (N=9). Dynamic susceptibility-contrast MRI and magnetic resonance angiography corroborated HP. Hyperperfusion preceded T2 increase in some animals, but HP and T2 changes temporally coincided in others. T2 peaked first at 24 hours whereas HP peaked at 48 hours after occlusion, and HP resolved by day 7 in most animals at which point the arteries became tortuous. Pixel-by-pixel tracking analysis showed that tissue did not infarct (migrated from core or mismatch at 30 minutes to normal at 48 hours) showed normal cerebral blood flow (CBF), whereas infarct tissue (migrated from core or mismatch at 30 minutes to infarct at 48 hours) showed exaggerated CBF, indicating that HP was associated with poor outcome.

Acupuncture attenuates neuronal cell death in middle cerebral artery occlusion model of focal ischemia

Objectives: This study was designed to investigate the neuroprotective effect of acupuncture in the middle cerebral artery occlusion-induced ischemia model.Methods: Sprague–Dawley rats were randomly divided into two experimental groups: middle cerebral artery occlusion group (MCAO, n=8), and middle cerebral artery occlusion plus acupuncture group (MCAO + Acu, n=8). Acupuncture stimulation was given immediately after reperfusion. The effect of its stimulation to both GB34 and GB39 on the size of the brain infarct and the functional status of the brain cells after middle cerebral artery occlusion was examined by nissl staining and neuron-specific nuclear protein immunohistochemistry.Results: The infarction volume was significantly decreased in the MCAO + Acu group (16.4 ± 4.8%), compared with the MCAO group (39.9 ± 10.2%). The number of neuron-specific nuclear protein-positive cells in the MCAO group was significantly decreased by 42.3 ± 12.6% in the striatum and by 45.8 ± 5.8% in the motor cortex, but the neuron-specific nuclear protein-positive cells in the MCAO + Acu group were rescued by 67.0 ± 3.8% in the striatum and by 68.1 ± 4.5% in the motor cortex, compared with the contralateral side (100%).Discussion: This study showed that acupuncture had neuroprotective effects against focal ischemia in the middle cerebral artery occlusion model.

Ubiquitin C‐terminal hydrolase‐L1 as a biomarker for ischemic and traumatic brain injury in rats

Ubiquitin C-terminal hydrolase-L1 (UCH-L1), also called neuronal-specific protein gene product 9.5, is a highly abundant protein in the neuronal cell body and has been identified as a possible biomarker on the basis of a recent proteomic study. In this study, we examined whether UCH-L1 was significantly elevated in cerebrospinal fluid (CSF) following controlled cortical impact (CCI) and middle cerebral artery occlusion (MCAO; model of ischemic stroke) in rats. Quantitative immunoblots of rat CSF revealed a dramatic elevation of UCH-L1 protein 48 h after severe CCI and as early as 6 h after mild (30 min) and severe (2 h) MCAO. A sandwich enzyme-linked immunosorbent assay constructed to measure UCH-L1 sensitively and quantitatively showed that CSF UCH-L1 levels were significantly elevated as early as 2 h and up to 48 h after CCI. Similarly, UCH-L1 levels were also significantly elevated in CSF from 6 to 72 h after 30 min of MCAO and from 6 to 120 h after 2 h of MCAO. These data are comparable to the profile of the calpain-produced alphaII-spectrin breakdown product of 145 kDa biomarker. Importantly, serum UCH-L1 biomarker levels were also significantly elevated after CCI. Similarly, serum UCH-L1 levels in the 2-h MCAO group were significantly higher than those in the 30-min group. Taken together, these data from two rat models of acute brain injury strongly suggest that UCH-L1 is a candidate brain injury biomarker detectable in biofluid compartments (CSF and serum).

Intravenous Administration of 99mTc-HMPAO-Labeled Human Mesenchymal Stem Cells after Stroke: In Vivo Imaging and Biodistribution

Human mesenchymal stem cells (hMSC) are a promising source for cell therapy after stroke. To deliver these cells, an IV injection appears safer than a local graft. We aimed to assess the whole-body biodistribution of IV-injected (99m)Tc-HMPAO-labeled hMSC in normal rats (n = 9) and following a right middle cerebral artery occlusion (MCAo, n = 9). Whole-body nuclear imaging, isolated organ counting (at 2 and 20 h after injection) and histology were performed. A higher activity was observed in the right damaged hemisphere of the MCAo group [6.5 +/- 0.9 x 10(-3) % of injected dose (ID)/g] than in the control group (3.6 +/- 1.2 x 10(-3) %ID/g), 20 h after injection. In MCAo rats, right hemisphere activity was higher than that observed in the contralateral hemisphere at 2 h after injection (11.6 +/- 2.8 vs. 9.8 +/- 1.7 x 10(-3) %ID/g). Following an initial hMSC lung accumulation, there was a decrease in pulmonary activity from 2 to 20 h after injection in both groups. The spleen was the only organ in which activity increased between 2 and 20 h. The presence of hMSC was documented in the spleen, liver, lung, and brain following histology. IV-injected hMSC are transiently trapped in the lungs, can be sequestered in the spleen, and are predominantly eliminated by kidneys. After 20 h, more hMSC are found in the ischemic lesion than into the undamaged cerebral tissue. IV delivery of hMSC could be the initial route for a clinical trial of tolerance.

Effects of the PDE5-inhibitor vardenafil in a mouse stroke model

Recent experimental studies in rodents suggest that treatment with inhibitors of phosphodiesterase type 5 (PDE5) (tadalafil, sildenafil, zaprinast) not only increases cerebral blood flow but also improves functional recovery after stroke. Here, we investigated in a mouse model of stroke the effects of vardenafil on survival, functional outcome and lesion size after experimental stroke. Mice were subjected to experimental stroke by occlusion of the middle cerebral artery (MCAO) for 45 min. A group of mice received vardenafil (twice 10 mg/kg body weight per day orally over 14 days) starting 3 h after MCAO. Control animals received the vehicle only. Survival, body weight, and behavior were monitored over 4 weeks and brain lesions were measured by T2-weighted MRI, hematoxylin/eosin — as well as GFAP-staining of cryostat sections, subsequently. The mortality in MCAO-operated animals amounted to 45% until day 10 after stroke and no significant difference in survival between the vardenafil- and vehicle-treatment groups was observed. Compared to sham-operated animals, MCAO-operated mice from both treatment groups demonstrated a significant weight loss until day 5 and regained their body weight by day 14 after ischemia. There was no significant difference between the vardenafil and vehicle-treated MCAO groups. In behavioral studies (sucrose consumption and pole test), analyzing sensorimotor functions as well as a parameter of depression-like symptoms, we observed no significant effect of vardenafil treatment on functional recovery in our model of stroke. Although we observed a trend towards less hemispherical atrophy in the vardenafil compared to the vehicle-treated group four weeks after MCAO our data do not suggest a functionally relevant CNS-tissue protective or regenerative effect in murine stroke.

The Effect Of Swimming Training On Neurogenesis In The Hippocampal Dentate Gyrus And Functional Ability After Focal Ischemic Stroke In Rats

The present study was aimed at investigating the effect of swimming training on brain function after focal cerebral ischemia in rats. PURPOSE: This study was examined on neurogenesis in dentate gyrus of hippocampus using 5-bromo-2′-deoxyuridine (BrdU) to label proliferating cells and assessed the neurological response following focal cerebral ischemia in rats using neurological motor behavioral test. METHODS: In an observer-blinded fashion twenty male Sprague-Dawley (280~310g, 7 weeks old) rats were divided into four groups: MCAO plus swimming group (ME, n1 =5), MCAO plus control group (MC, n2 =5), SHAM plus swimming group (SE, n3 =5), SHAM plus control group (SC, n4 =5). RESULTS: The limb placing time before and after swimming in the ME group were significantly longer than he MC group (p<.05), the SE group were significantly longer than the SC group (p<.01). The balance beam scores before and after swimming in the ME group was higher than the SE group, the MC group was higher than the SC group but was not significantly difference. The foot fault index before and after swimming training in ME group was significantly lower (i.e., im proved) than the MC group (p<.001) and the SE group (p<.001), the SE group was significantly lower (i.e., improved) than the SC group (p<.001). The mean number of BrdU-positive cells in the dentate gyrus in the ME group was significantly higher than the MC group (p<.001) and the SE group (p<.01). The MC group and the SE group was sig nificantly higher than the SC group (p<.001). There was significantly correlation between limb placing time and number of BrdU-positive cells on swimming training, there is positive correlation (r=0.807, p=.000) and between foot fault index and BrdU-positive cells number, there is negative correlation (r=−0.503, p=.05). However, between balance beam scores and BrdU-positive cells number, there is no correlation. CONCLUSION: The present study demonstrates that the role of swimming training improves behavioral motor function probably by enhancing cell proliferation in that hippocampus.

Comparison of two rat models of cerebral ischemia under hyperglycemic conditions

Hyperglycemia worsens outcome of stroke either in the clinical setting or in animal models. In the present study, two focal cerebral ischemia models, permanent middle cerebral artery occlusion (MCAO, 3-4 h) and reversible MCAO (1 h ischemia + 3 h reperfusion), under hyperglycemic conditions were compared. Using 2,3,5-triphenyltetrazolium chloride staining to define viable tissue, this resulted in the infarction area being confined primarily to the cerebral cortex in the permanent MCAO group, while it extended to the subcortical area in the reversible MCAO group, and the lesion areas were respectively 27.7 +/- 5.3% and 46.8 +/- 12.0% of the ipsilateral hemisphere (P = 0.012). Hyperglycemia accelerated the cerebral damage compared to normoglycemia and ascorbic acid pre-treatment maintained tissue viability during the acute phase of hyperglycemic MCAO. In conclusion, hyperglycemia combined with either of the two MCAO models resulted in rapid infarction associated with increased oxidative stress. The hyperglycemic models are suitable for pharmaceutical therapeutic studies of antioxidant efficacy.

A new model of focal cerebral ischemia in the miniature pig

The purpose of this set of studies is to design a minimally invasive, reproducible stroke model in the gyrencephalic brain. This paper provides information on both surgical technique and methods of quantification of ischemic damage to both gray and white matter in the miniature pig. Sixteen male miniature pigs were randomly divided into three groups and underwent transcranial surgery involving a frontotemporal approach with orbital rim osteotomy for permanent middle cerebral artery occlusion (MCAO; five animals), permanent internal carotid artery occlusion (ICAO; six animals), and a sham operation (five animals). Histological mapping and magnetic resonance (MR) imaging were used to delineate the areas of ischemic damage. The volumes of infarction measured directly from MR images were 16.2 +/- 1.1, 1.5 +/- 0.5, and 0.0 +/- 0.0 cm3 (mean +/- standard deviation [SD], p < 0.001) in the MCAO, ICAO, and sham-operated groups, respectively. The areas of ischemia identified through histological analysis and MR imaging showed a good correlation (r2 = 0.86, p < 0.0001). Immunohistochemical staining with an amyloid precursor protein (APP) antibody was used to evaluate axonal damage and calculate a total APP score for axonal damage of 44.8 +/- 2.9 in the MCAO, 13.2 +/- 6.6 in the ICAO, and 0.0 +/- 0.0 (mean +/- SD, p < 0.002) in the sham-operated animals. This new model of focal cerebral ischemia induces a reproducible amount of ischemic damage in both gray and white matter, and has significant utility for studies of the pathophysiology of ischemia in the gyrencephalic brain and for assessment of the therapeutic efficacy of drugs prior to the initiation of human clinical trials.

A temporal MRI assessment of neuropathology after transient middle cerebral artery occlusion in the rat: correlations with behavior.

The purpose of this study was to evaluate the temporal and spatial pathological alterations within ischemic tissue using serial magnetic resonance imaging (MRI) and to determine the extent and duration of functional impairment using objective behavioral tests after transient middle cerebral artery occlusion (tMCAO) in the rat. MRI signatures derived from specific anatomical regions of interest (ROI) were then appropriately correlated to the behavioral measures over the time course of the study (up to 28 days post-tMCAO). Sprague-Dawley rats (n = 12) were initially trained on the following behavioral tasks before surgery: bilateral sticky label test (for contralateral neglect); beam walking (for hindlimb coordination); staircase test (for skilled forelimb paw-reaching). Rats were then randomly assigned to receive either tMCAO (90 minutes, n = 6), by means of the intraluminal thread technique, or sham-control surgery (n = 6). Proton density, T2- and T2-diffusion-weighted MR images were acquired at 1, 7, 14, and 28 days post-tMCAO that were then smoothed into respective proton density, T2 relaxation, and apparent diffusion coefficient (ADC) maps. Apparent percent total lesion volume was assessed using T2W imaging. MR signatures were evaluated using the tissue maps by defining ROI for MCAO and sham-control groups, which corresponded to the caudate-putamen, forelimb, hindlimb, and lower parietal cortices both ipsilateral and contralateral to the occlusion site. Behavioral tests were undertaken daily from 1 to 28 days post-tMCAO. Results demonstrate that apparent percent lesion volume reduced from 1 to 7 days (P < 0.05) but then remained constant up to 28 days for the MCAO group. Pathological changes in the temporal profile of T2 and ADC tissue signatures were significantly altered in specific ROI across the time course of the study (P < 0.05 to <0.001), reflecting the progression of edema to necrosis and cavitation. Both T2 and ADC measures of ischemic pathology correlated with parameters defined by each of the functional tests (r > or =0.5, P < 0.05) across the time course. The staircase test revealed bilateral impairments for the MCAO group (P <0.001), which were best predicted by damage to the ipsilateral lower parietal cortex by means of hierarchical multiple regression analyses (R2 changes > or =0.21, P < or =0.03). Behavioral recovery was apparent on the beam walking test at 14 to 28 days post-MCAO, which was mirrored by MRI signatures within the hindlimb cortex returning to sham-control levels. This long-term study is the first of its kind in tracing the dynamic pathologic and functional consequences of tMCAO in the rat. Both serial MRI and objective behavioral assessment provide highly suitable outcome measures that can be effectively used to evaluate promising new antiischemic agents targeted for the clinic.

The Glycine Antagonist GV150526 Protects Somatosensory Evoked Potentials and Reduces the Infarct Area in the MCAo Model of Focal Ischemia in the Rat

The neuroprotective activity of the novel, selective glycine antagonist GV150526 was assessed in the middle artery occlusion (MCAo) model of focal ischemia. Postischemia administration of GV150526 (3 mg/kg iv) up to 6 h post-MCAo resulted in a significant reduction of the infarct volume measured histologically 24 h later. The neuronal protection by GV150526 was accompanied by functionally significant protection determined by somatosensory evoked potential (SEP) responses recorded from the primary somatosensory cortex of rats under urethane anesthesia. Experimental occlusion of the MCA 7 days prior to electrophysiological testing induced a clear reduction in the SEP amplitude. GV150526 (3mg/kg, iv) was able to protect SEP responses recorded from the hindpaw cortical field in two groups of animals treated either 1 (n=9) or 6 h (n=10) post-MCAo. SEP responses recorded from the forepaw cortical field, an area closer to the core of the ischemic damage, were significantly protected only in the group treated 1 h post-MCAo. Histological evaluation of the rat brain regions showed a correlated decrease in the ischemic area of GV150526-treated groups. The volumes of the ischemic brains of both GV150526 groups were statistically different from the MCAo group (P<0.05). These findings demonstrate that GV150526 is able to prevent the ischemic damage assessed histologically and affect the functional correlates of the ischemia evaluated by the electrophysiological SEP measurements.

Effects of protein kinase C agonists on Na,K-ATPase activity in rat brain microvessels.

In order to study the possible role of C kinase (PKC) on sodium pump of cerebral vessels, we used diacylglycerol (diC8: sn-1,2-dioctanoylglycerol) and phorbol esters (PMA: phorbol 12-myr-istate 13-acetate; PDA: phorbol 12,13-diacetate; 4 oc-P: 4-alpha phorbol) as PKC activators, and examined their effects on Na, KATPase activity in rat brain microvessels (MVs). Rats were divided into non-treated (control; n = 9), four-vessel occlusion (4VO; 30-30 minutes ischemia and recirculation, n = 5), and middle cerebral artery occlusion (MCAO, n = 3) groups. MVs were passed through nylon meshes and were obtained by ultracentrifuge at 58000 g. Na,K-ATPase activity in MVs was determined by the phosphomolybdate method. DiC8 enhanced Na,K-ATPase activity at 10-4M in the control group, the 4VO group and the contralateral hemispheres of the MCAO group (139% ± 0.06**, 135% ± 0.2*, 133% ± 0.18, mean ± SE, * p < 0.05, ** p < 0.01, Wilcoxon rank sum) respectively, but had no effects on MVs in the ipsilateral hemispheres of MCAO group (-74% ± 0.04). This activation by diC8 was inhibited by PKC inhibitors, staurosporine (3 x 10-8M) and H7 (l0-6M) in the control MVs. By contrast, PMA suppressed Na, KATPase at 10-5M in the control group (-25% ±0.07*), but it tended to activate Na,K-ATPase activity in the ipsilateral hemispheres of the MCAO groups (33% ± 0.09). PDA and 4 α-P did not have any consistent effects at the concentration examined. The cause of difference between the effects of diC8 and PMA is unclear at present, but it may stem from the mode of lipid-membrane interaction in these agents and the difference in the condition of cells as well.

CJ89-34. A study of negative pressures in oil films and the load carrying mechanism of oil film between two rough surfaces : By Wu Chengwei and Zheng Linqing (Tsinghua University, Beijing, China). Chinese J. Mech. Engng25, No. 3 (Sept., 1989), pp. 19–23

Characterization of functional outcome in animal stroke models is essential to improve preclinical drug screenings. Operant procedures showed promising results for the identification of long-lasting functional deficits. In particular, a suppression of lever-pressing in high ratio schedules has been consistently found in rodent models of ischemic stroke. In the present work, we attempted to replicate these isolated observations, by submitting C57Bl/6J mice to a progressive fixed-ratio schedule of reinforcement three weeks after MCAO or sham surgery. Results showed a significant lever-pressing impairment in the MCAO group. Motivational factors (longer post-reinforcement pause, lesser appeal for food rewards) seemed accountable for the deficit, while motor abilities appeared preserved. These findings resemble fatigue-like states experienced by stroke survivors and may be used as long-term measures of behavioral outcome following experimental stroke.

CJ89-35. A new method to assess the stability in the dynamic performance of machine-tool : By Xiao Youyi and Peng Zemin (Tianjin University, Tianjin, China). Chinese J. Mech. Engng25, No. 3 (Sept., 1989), pp. 24–30

Characterization of functional outcome in animal stroke models is essential to improve preclinical drug screenings. Operant procedures showed promising results for the identification of long-lasting functional deficits. In particular, a suppression of lever-pressing in high ratio schedules has been consistently found in rodent models of ischemic stroke. In the present work, we attempted to replicate these isolated observations, by submitting C57Bl/6J mice to a progressive fixed-ratio schedule of reinforcement three weeks after MCAO or sham surgery. Results showed a significant lever-pressing impairment in the MCAO group. Motivational factors (longer post-reinforcement pause, lesser appeal for food rewards) seemed accountable for the deficit, while motor abilities appeared preserved. These findings resemble fatigue-like states experienced by stroke survivors and may be used as long-term measures of behavioral outcome following experimental stroke.

CJ89-32. A study of surface formation in cutting process of fine ceramics : By Jin Dongxie (Harbin University of Science and Technology, Harbin, Heilongjiang, China). Chinese J. Mech. Engng25, No. 3 (Sept., 1989), pp. 8–12

Characterization of functional outcome in animal stroke models is essential to improve preclinical drug screenings. Operant procedures showed promising results for the identification of long-lasting functional deficits. In particular, a suppression of lever-pressing in high ratio schedules has been consistently found in rodent models of ischemic stroke. In the present work, we attempted to replicate these isolated observations, by submitting C57Bl/6J mice to a progressive fixed-ratio schedule of reinforcement three weeks after MCAO or sham surgery. Results showed a significant lever-pressing impairment in the MCAO group. Motivational factors (longer post-reinforcement pause, lesser appeal for food rewards) seemed accountable for the deficit, while motor abilities appeared preserved. These findings resemble fatigue-like states experienced by stroke survivors and may be used as long-term measures of behavioral outcome following experimental stroke.

CJ89-31. A study of the criterion for ceramic tool fracture in intermittent turning steel : By Ai Xing and Xia Chuanbo (Shandong Polytechnic University, Jinan, Shandong, China). Chinese J. Mech. Engng25, No. 3 (Sept., 1989), pp. 1–7

Characterization of functional outcome in animal stroke models is essential to improve preclinical drug screenings. Operant procedures showed promising results for the identification of long-lasting functional deficits. In particular, a suppression of lever-pressing in high ratio schedules has been consistently found in rodent models of ischemic stroke. In the present work, we attempted to replicate these isolated observations, by submitting C57Bl/6J mice to a progressive fixed-ratio schedule of reinforcement three weeks after MCAO or sham surgery. Results showed a significant lever-pressing impairment in the MCAO group. Motivational factors (longer post-reinforcement pause, lesser appeal for food rewards) seemed accountable for the deficit, while motor abilities appeared preserved. These findings resemble fatigue-like states experienced by stroke survivors and may be used as long-term measures of behavioral outcome following experimental stroke.

CJ89-33. A new approach to the mechanism of wear particle formation and growth : By Jia Chunde (Shenyang Institute of Technology, Shenyang, Liaonin, China) and J. S. Sheasby (The University of Western Ontario, Canada). Chinese J. Mech. Engng25, No. 3 (Sept., 1989), pp. 13–18

Characterization of functional outcome in animal stroke models is essential to improve preclinical drug screenings. Operant procedures showed promising results for the identification of long-lasting functional deficits. In particular, a suppression of lever-pressing in high ratio schedules has been consistently found in rodent models of ischemic stroke. In the present work, we attempted to replicate these isolated observations, by submitting C57Bl/6J mice to a progressive fixed-ratio schedule of reinforcement three weeks after MCAO or sham surgery. Results showed a significant lever-pressing impairment in the MCAO group. Motivational factors (longer post-reinforcement pause, lesser appeal for food rewards) seemed accountable for the deficit, while motor abilities appeared preserved. These findings resemble fatigue-like states experienced by stroke survivors and may be used as long-term measures of behavioral outcome following experimental stroke.