scholarly journals Delayed Reperfusion Deficits after Experimental Stroke Account for Increased Pathophysiology

2014 ◽  
Vol 35 (2) ◽  
pp. 277-284 ◽  
Author(s):  
Fiona E Burrows ◽  
Natasha Bray ◽  
Adam Denes ◽  
Stuart M Allan ◽  
Ingo Schiessl
Keyword(s):  
Ischemic Stroke ◽  
Artery Occlusion ◽  
Therapeutic Interventions ◽  
Experimental Stroke ◽  
Initial Increase ◽  
Significant Drop ◽  
Sham Surgery ◽  
Interleukin 1Α ◽  
Oxygen Perfusion ◽  
Cerebral Artery Occlusion

Cerebral blood flow and oxygenation in the first few hours after reperfusion following ischemic stroke are critical for therapeutic interventions but are not well understood. We investigate changes in oxyhemoglobin (HbO2) concentration in the cortex during and after ischemic stroke, using multispectral optical imaging in anesthetized mice, a remote filament to induce either 30 minute middle cerebral artery occlusion (MCAo), sham surgery or anesthesia alone. Immunohistochemistry establishes cortical injury and correlates the severity of damage with the change of oxygen perfusion. All groups were imaged for 6 hours after MCAo or sham surgery. Oxygenation maps were calculated using a pathlength scaling algorithm. The MCAo group shows a significant drop in HbO2 during occlusion and an initial increase after reperfusion. Over the subsequent 6 hours HbO2 concentrations decline to levels below those observed during stroke. Platelets, activated microglia, interleukin-1α, evidence of BBB breakdown and neuronal stress increase within the stroked hemisphere and correlate with the severity of the delayed reperfusion deficit but not with the ΔHbO2 during stroke. Despite initial restoration of HbO2 after 30 min MCAo there is a delayed compromise that coincides with inflammation and could be a target for improved stroke outcome after thrombolysis.

scholarly journals CD28 Superagonist-Mediated Boost of Regulatory T Cells Increases Thrombo-Inflammation and Ischemic Neurodegeneration during the Acute Phase of Experimental Stroke

2014 ◽  
Vol 35 (1) ◽  
pp. 6-10 ◽  
Author(s):  
Michael K Schuhmann ◽  
Peter Kraft ◽  
Guido Stoll ◽  
Kristina Lorenz ◽  
Sven G Meuth ◽  
...  
Keyword(s):  
T Cells ◽  
Ischemic Stroke ◽  
Regulatory T Cells ◽  
Thrombus Formation ◽  
Inflammatory Lesion ◽  
Artery Occlusion ◽  
Acute Stage ◽  
Experimental Stroke ◽  
Cerebral Artery Occlusion

While the detrimental role of non-regulatory T cells in ischemic stroke is meanwhile unequivocally recognized, there are controversies about the properties of regulatory T cells (Treg). The aim of this study was to elucidate the role of Treg by applying superagonistic anti-CD28 antibody expansion of Treg. Stroke outcome, thrombus formation, and brain-infiltrating cells were determined on day 1 after transient middle cerebral artery occlusion. Antibody-mediated expansion of Treg enhanced stroke size and worsened functional outcome. Mechanistically, Treg increased thrombus formation in the cerebral microvasculature. These findings confirm that Treg promote thrombo-inflammatory lesion growth during the acute stage of ischemic stroke.

scholarly journals Effects of Tetramethylpyrazine on Functional Recovery and Neuronal Dendritic Plasticity after Experimental Stroke

2015 ◽  
Vol 2015 ◽  
pp. 1-10 ◽  
Author(s):  
Jun-Bin Lin ◽  
Chan-Juan Zheng ◽  
Xuan Zhang ◽  
Juan Chen ◽  
Wei-Jing Liao ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Functional Recovery ◽  
Classical Model ◽  
Significant Negative Correlation ◽  
Artery Occlusion ◽  
Neurological Function ◽  
Experimental Stroke ◽  
Spine Density ◽  
Dendritic Plasticity ◽  
Cerebral Artery Occlusion

The 2,3,5,6-tetramethylpyrazine (TMP) has been widely used in the treatment of ischemic stroke by Chinese doctors. Here, we report the effects of TMP on functional recovery and dendritic plasticity after ischemic stroke. A classical model of middle cerebral artery occlusion (MCAO) was established in this study. The rats were assigned into 3 groups: sham group (sham operated rats treated with saline), model group (MCAO rats treated with saline) and TMP group (MCAO rats treated with 20 mg/kg/d TMP). The neurological function test of animals was evaluated using the modified neurological severity score (mNSS) at 3 d, 7 d, and 14 d after MCAO. Animals were euthanized for immunohistochemical labeling to measure MAP-2 levels in the peri-infarct area. Golgi-Cox staining was performed to test effect of TMP on dendritic plasticity at 14 d after MCAO. TMP significantly improved neurological function at 7 d and 14 d after ischemia, increased MAP-2 level at 14 d after ischemia, and enhanced spine density of basilar dendrites. TMP failed to affect the spine density of apical dendrites and the total dendritic length. Data analyses indicate that there was significant negative correlation between mNSS and plasticity measured at 14 d after MCAO. Thus, enhanced dendritic plasticity contributes to TMP-elicited functional recovery after ischemic stroke.

scholarly journals The Hsp90 Inhibitor 17-DMAG Attenuates Hyperglycemia-Enhanced Hemorrhagic Transformation in Experimental Stroke

2021 ◽  
Vol 2021 ◽  
pp. 1-7
Author(s):  
Jiaming Zhang ◽  
Kai Wang ◽  
Jia Qi ◽  
Xiaodong Cao ◽  
Feng Wang
Keyword(s):  
Ischemic Stroke ◽  
Hsp90 Inhibitor ◽  
Hemorrhagic Transformation ◽  
Artery Occlusion ◽  
Vital Role ◽  
Experimental Stroke ◽  
Acute Hyperglycemia ◽  
Inflammatory Molecules ◽  
Cerebral Artery Occlusion ◽  
The Brain

Introduction. Hemorrhagic transformation (HT) is one of the most common complications of ischemic stroke which is exacerbated by hyperglycemia. Oxidative stress, inflammatory response, and matrix metalloproteinases (MMPs) have been evidenced to play a vital role in the pathophysiology of HT. Our previous study has reported that 17-DMAG, an Hsp90 inhibitor, protects the brain against ischemic injury via inhibiting inflammation and reducing MMP-9 after ischemia. However, whether 17-DMAG would attenuate HT in hyperglycemic middle cerebral artery occlusion (MCAO) rats is still unknown. Methods. Acute hyperglycemia was induced by an injection of 50% dextrose. Rats were pretreated with 17-DMAG before MCAO. Infarction volume, hemorrhagic volume neurological scores, expressions of inflammatory molecules and tight junction proteins, and activity of MMP-2 and MMP-9 were assessed 24 h after MCAO. Results. 17-DMAG was found to reduce HT, improve neurological function, and inhibit expressions of inflammatory molecules and the activation of MMPs at 24 h after MCAO. Conclusion. These results implicated that Hsp90 could be a novel therapeutic target in HT following ischemic stroke.

scholarly journals Improved reperfusion following alternative surgical approach for experimental stroke in mice

F1000Research ◽  
2020 ◽  
Vol 9 ◽  
pp. 188
Author(s):  
Melissa Trotman-Lucas ◽  
Raymond Wong ◽  
Stuart M. Allan ◽  
Claire L. Gibson
Keyword(s):  
Ischemic Stroke ◽  
Surgical Approach ◽  
Artery Occlusion ◽  
Laser Speckle ◽  
Experimental Stroke ◽  
Contrast Imaging ◽  
Ipsilateral Hemisphere ◽  
Cerebral Artery Occlusion ◽  
The Brain

Background: Following ischemic stroke, recanalisation and restoration of blood flow to the affected area of the brain is critical and directly correlates with patient recovery.  In vivo models of ischemic stroke show high variability in outcomes, which may be due to variability in reperfusion.  We previously reported that a surgical refinement in the middle cerebral artery occlusion (MCAO) model of stroke, via repair of the common carotid artery (CCA), removes the reliance on the Circle of Willis for reperfusion and reduced infarct variability.  Here we further assess this refined surgical approach on reperfusion characteristics following transient MCAO in mice. Methods: Mice underwent 60 min of MCAO, followed by either CCA repair or ligation at reperfusion.  All mice underwent laser speckle contrast imaging at baseline, 24 h and 48 h post-MCAO. Results: CCA ligation reduced cerebral perfusion in the ipsilateral hemisphere compared to baseline (102.3 ± 4.57%) at 24 h (85.13 ± 16.09%; P < 0.01) and 48 h (75.04 ± 12.954%; P < 0.001) post-MCAO. Repair of the CCA returned perfusion to baseline (94.152 ± 2.44%) levels and perfusion was significantly improved compared to CCA ligation at both 24 h (102.83 ± 8.41%; P < 0.05) and 48 h (102.13 ± 9.34%; P < 0.001) post-MCAO. Conclusions: Our findings show CCA repair, an alternative surgical approach for MCAO, results in improved ischemic hemisphere perfusion during the acute phase.

scholarly journals Infarct Growth Precedes Cerebral Thrombosis Following Experimental Stroke in Mice

2021 ◽  
Author(s):  
Vanessa Göb ◽  
Maximilian G. Voll ◽  
Lena Zimmermann ◽  
Katherina Hemmen ◽  
Guido Stoll ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Tissue Damage ◽  
Thrombus Formation ◽  
Brain Slices ◽  
Light Sheet ◽  
Artery Occlusion ◽  
Experimental Stroke ◽  
Cerebral Thrombosis ◽  
Cerebral Artery Occlusion ◽  
Kinetics Of

Abstract Ischemic stroke is among the leading causes of disability and death worldwide. In acute ischemic stroke, successful recanalization of occluded vessels is the primary therapeutic aim, but even if it is achieved, not all patients benefit. Although blockade of platelet aggregation did not prevent infarct progression, cerebral thrombosis as cause of secondary infarct growth has remained a matter of debate. As cerebral thrombi are frequently observed after experimental stroke, a thrombus-induced impairment of the brain microcirculation is considered to contribute to tissue damage. Here, we combine the model of transient middle cerebral artery occlusion (tMCAO) with light sheet fluorescence microscopy and immunohistochemistry of brain slices to investigate the kinetics of thrombus formation and infarct progression. Our data reveal that tissue damage already peaks after 8 h of reperfusion following 60 min MCAO, while cerebral thrombi are only observed at later time points. Thus, cerebral thrombosis is not causative for secondary infarct growth during ischemic stroke.

scholarly journals Improved reperfusion following alternative surgical approach for experimental stroke in mice

F1000Research ◽  
2020 ◽  
Vol 9 ◽  
pp. 188
Author(s):  
Melissa Trotman-Lucas ◽  
Raymond Wong ◽  
Stuart M. Allan ◽  
Claire L. Gibson
Keyword(s):  
Ischemic Stroke ◽  
Surgical Approach ◽  
Artery Occlusion ◽  
Laser Speckle ◽  
Experimental Stroke ◽  
Contrast Imaging ◽  
Ipsilateral Hemisphere ◽  
Cerebral Artery Occlusion ◽  
The Brain

Background: Following ischemic stroke, recanalisation and restoration of blood flow to the affected area of the brain is critical and directly correlates with patient recovery.  In vivo models of ischemic stroke show high variability in outcomes, which may be due to variability in reperfusion.  We previously reported that a surgical refinement in the middle cerebral artery occlusion (MCAO) model of stroke, via repair of the common carotid artery (CCA), removes the reliance on the Circle of Willis for reperfusion and reduced infarct variability.  Here we further assess this refined surgical approach on reperfusion characteristics following transient MCAO in mice. Methods: Mice underwent 60 min of MCAO, followed by either CCA repair or ligation at reperfusion.  All mice underwent laser speckle contrast imaging at baseline, 24 h and 48 h post-MCAO. Results: CCA ligation reduced cerebral perfusion in the ipsilateral hemisphere compared to baseline (102.3 ± 4.57%) at 24 h (85.13 ± 16.09%; P < 0.01) and 48 h (75.04 ± 12.954%; P < 0.001) post-MCAO. Repair of the CCA returned perfusion to baseline (94.152 ± 2.44%) levels and perfusion was significantly improved compared to CCA ligation at both 24 h (102.83 ± 8.41%; P < 0.05) and 48 h (102.13 ± 9.34%; P < 0.001) post-MCAO. Conclusions: Our findings show CCA repair, an alternative surgical approach for MCAO, results in improved ischemic hemisphere perfusion during the acute phase.

scholarly journals Improved reperfusion following alternative surgical approach for experimental stroke in mice

F1000Research ◽  
2020 ◽  
Vol 9 ◽  
pp. 188
Author(s):  
Melissa Trotman-Lucas ◽  
Raymond Wong ◽  
Stuart M. Allan ◽  
Claire L. Gibson
Keyword(s):  
Ischemic Stroke ◽  
Surgical Approach ◽  
Artery Occlusion ◽  
Laser Speckle ◽  
Experimental Stroke ◽  
Contrast Imaging ◽  
Ipsilateral Hemisphere ◽  
Cerebral Artery Occlusion ◽  
The Brain

Background: Following ischemic stroke, recanalisation and restoration of blood flow to the affected area of the brain is critical and directly correlates with patient recovery.  In vivo models of ischemic stroke show high variability in outcomes, which may be due to variability in reperfusion.  We previously reported that a surgical refinement in the middle cerebral artery occlusion (MCAO) model of stroke, via repair of the common carotid artery (CCA), removes the reliance on the Circle of Willis for reperfusion and reduced infarct variability.  Here we further assess this refined surgical approach on reperfusion characteristics following transient MCAO in mice. Methods: Mice underwent 60 min of MCAO, followed by either CCA repair or ligation at reperfusion.  All mice underwent laser speckle contrast imaging at baseline, 24 h and 48 h post-MCAO. Results: CCA ligation reduced cerebral perfusion in the ipsilateral hemisphere compared to baseline (102.3 ± 4.57%) at 24 h (85.13 ± 16.09%; P < 0.01) and 48 h (75.04 ± 12.954%; P < 0.001) post-MCAO. Repair of the CCA returned perfusion to baseline (94.152 ± 2.44%) levels and perfusion was significantly improved compared to CCA ligation at both 24 h (102.83 ± 8.41%; P < 0.05) and 48 h (102.13 ± 9.34%; P < 0.001) post-MCAO. Conclusions: Our findings show CCA repair, an alternative surgical approach for MCAO, results in improved ischemic hemisphere perfusion during the acute phase.

Plasma arginine-vasopressin following experimental stroke: effect of osmotherapy

2006 ◽  
Vol 100 (5) ◽  
pp. 1445-1451 ◽  
Author(s):  
Yi Chang ◽  
Tsung-Ying Chen ◽  
Chih-Hung Chen ◽  
Barbara J. Crain ◽  
Thomas J. K. Toung ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Middle Cerebral Artery ◽  
Water Content ◽  
Middle Cerebral Artery Occlusion ◽  
Cerebral Artery ◽  
Arginine Vasopressin ◽  
Artery Occlusion ◽  
Experimental Stroke ◽  
Plasma Arginine ◽  
Cerebral Artery Occlusion

Neurohumoral responses have been implicated in the pathogenesis of ischemia-evoked cerebral edema. In a well-characterized animal model of ischemic stroke, the present study was undertaken to 1) study the profile of plasma arginine-vasopressin (AVP), and 2) determine whether osmotherapy with mannitol and various concentrations of hypertonic saline (HS) solutions influence plasma AVP levels. Halothane-anesthetized adult male Wistar rats were subjected to 2 h of middle cerebral artery occlusion with the intraluminal filament technique. Plasma AVP levels (means ± SD) were significantly elevated at 24 h (42 ± 21 pg/ml), 48 h (50 ± 28 pg/ml), and 72 h (110 ± 47 pg/ml), and returned to baseline at 96 h (22 ± 15 pg/ml) following middle cerebral artery occlusion compared with sham-operated controls (14 ± 7 pg/ml). Plasma AVP levels at 72 h were significantly attenuated with 7.5% HS (37 ± 8 pg/ml; 360 ± 11 osmol/l) compared with 0.9% saline (73 ± 6; 292 ± 6 osmol/l), 3% HS (66 ± 8 pg/ml; 303 ± 12 osmol/l), or mannitol (74 ± 9 pg/ml; 313 ± 14 osmol/l) treatment. HS (7.5%) significantly attenuated water content in the ipsilateral and contralateral hemispheres compared with surgical shams, 0.9% saline, 3% HS, and mannitol treatments. Peak plasma AVP levels were not associated with direct histopathological injury to the anterior hypothalamus. Attenuation of brain water content with 7.5% HS treatment coincides with attenuated serum AVP levels, and we speculate that this may represent one additional mechanism by which osmotherapy attenuates edema associated with ischemic stroke.

scholarly journals Infarct growth precedes cerebral thrombosis following experimental stroke in mice

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Vanessa Göb ◽  
Maximilian G. Voll ◽  
Lena Zimmermann ◽  
Katherina Hemmen ◽  
Guido Stoll ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Tissue Damage ◽  
Thrombus Formation ◽  
Brain Slices ◽  
Light Sheet ◽  
Artery Occlusion ◽  
Experimental Stroke ◽  
Cerebral Thrombosis ◽  
Cerebral Artery Occlusion ◽  
Kinetics Of

AbstractIschemic stroke is among the leading causes of disability and death worldwide. In acute ischemic stroke, successful recanalization of occluded vessels is the primary therapeutic aim, but even if it is achieved, not all patients benefit. Although blockade of platelet aggregation did not prevent infarct progression, cerebral thrombosis as cause of secondary infarct growth has remained a matter of debate. As cerebral thrombi are frequently observed after experimental stroke, a thrombus-induced impairment of the brain microcirculation is considered to contribute to tissue damage. Here, we combine the model of transient middle cerebral artery occlusion (tMCAO) with light sheet fluorescence microscopy and immunohistochemistry of brain slices to investigate the kinetics of thrombus formation and infarct progression. Our data reveal that tissue damage already peaks after 8 h of reperfusion following 60 min MCAO, while cerebral thrombi are only observed at later time points. Thus, cerebral thrombosis is not causative for secondary infarct growth during ischemic stroke.

Energy-Sensing Pathways in Ischemia: The Counterbalance Between AMPK and mTORC

2020 ◽  
Vol 25 (45) ◽  
pp. 4763-4770
Author(s):  
Angel Cespedes ◽  
Mario Villa ◽  
Irene Benito-Cuesta ◽  
Maria J. Perez-Alvarez ◽  
Lara Ordoñez ◽  
...  
Keyword(s):  
Blood Flow ◽  
Ischemic Stroke ◽  
Middle Cerebral Artery ◽  
Cause Of Death ◽  
Artery Occlusion ◽  
Brain Pathology ◽  
Common Cause ◽  
Specific Analysis ◽  
Energy Sensing ◽  
Cerebral Artery Occlusion

: Stroke is an important cause of death and disability, and it is the second leading cause of death worldwide. In humans, middle cerebral artery occlusion (MCAO) is the most common cause of ischemic stroke. The damage occurs due to the lack of nutrients and oxygen contributed by the blood flow. : The present review aims to analyze to what extent the lack of each of the elements of the system leads to damage and which mechanisms are unaffected by this deficiency. We believe that the specific analysis of the effect of lack of each component could lead to the emergence of new therapeutic targets for this important brain pathology.

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