scholarly journals Mesenchymal stromal cell-derived small extracellular vesicles promote neurological recovery and brain remodeling after distal middle cerebral artery occlusion in aged rats

GeroScience ◽  
2021 ◽  
Author(s):  
Danut-Adrian Dumbrava ◽  
Roxana Surugiu ◽  
Verena Börger ◽  
Mihai Ruscu ◽  
Tobias Tertel ◽  
...  
Keyword(s):  
Middle Cerebral Artery ◽  
Middle Cerebral Artery Occlusion ◽  
Brain Tissue ◽  
Motor Coordination ◽  
Artery Occlusion ◽  
Neurological Recovery ◽  
Aged Rats ◽  
Brdu Immunohistochemistry ◽  
Cerebral Artery Occlusion ◽  
Brain Macrophage

AbstractSmall extracellular vesicles (sEVs) obtained from mesenchymal stromal cells (MSCs) promote neurological recovery after middle cerebral artery occlusion (MCAO) in young rodents. Ischemic stroke mainly affects aged humans. MSC-sEV effects on stroke recovery in aged rodents had not been assessed. In a head-to-head comparison, we exposed young (4–5 months) and aged (19–20 months) male Sprague–Dawley rats to permanent distal MCAO. At 24 h, 3 and 7 days post-stroke, vehicle or MSC-sEVs (2 × 106 or 2 × 107 MSC equivalents/kg) were intravenously administered. Neurological deficits, ischemic injury, brain inflammatory responses, post-ischemic angiogenesis, and endogenous neurogenesis were evaluated over 28 days. Post-MCAO, aged vehicle-treated rats exhibited more severe motor-coordination deficits evaluated by rotating pole and cylinder tests and larger brain infarcts than young vehicle-treated rats. Although infarct volume was not influenced by MSC-sEVs, sEVs at both doses effectively reduced motor-coordination deficits in young and aged rats. Brain macrophage infiltrates in periinfarct tissue, which were evaluated as marker of a recovery-aversive inflammatory environment, were significantly stronger in aged than young vehicle-treated rats. sEVs reduced brain macrophage infiltrates in aged, but not young rats. The tolerogenic shift in immune balance paved the way for structural brain tissue remodeling. Hence, sEVs at both doses increased periinfarct angiogenesis evaluated by CD31/BrdU immunohistochemistry in young and aged rats, and low-dose sEVs increased neurogenesis in the subventricular zone examined by DCX/BrdU immunohistochemistry. Our study provides robust evidence that MSC-sEVs promote functional neurological recovery and brain tissue remodeling in aged rats post-stroke. This study encourages further proof-of-concept studies in clinic-relevant stroke settings.

scholarly journals Brain Tissue Concentrations of ATP, Phosphocreatine, Lactate, and Tissue pH in Relation to Reduced Cerebral Blood Flow following Experimental Acute Middle Cerebral Artery Occlusion

1988 ◽  
Vol 8 (6) ◽  
pp. 866-874 ◽  
Author(s):  
T. P. Obrenovitch ◽  
O. Garofalo ◽  
R. J. Harris ◽  
L. Bordi ◽  
M. Ono ◽  
...  
Keyword(s):  
Blood Flow ◽  
Middle Cerebral Artery ◽  
Middle Cerebral Artery Occlusion ◽  
Brain Tissue ◽  
Cerebral Artery ◽  
Artery Occlusion ◽  
Tissue Samples ◽  
Tissue Ph ◽  
Focal Ischaemia ◽  
Cerebral Artery Occlusion

Local CBF (LCBF) was compared with the corresponding local tissue concentration of ATP, phosphocreatine (PCr), and lactate in anaesthetized baboons subjected to focal ischaemia produced by middle cerebral artery occlusion (MCAO). LCBF hydrogen electrodes were implanted in cortical regions where MCAO had been previously shown to produce severe and penumbral ischaemia and in posterior regions where blood flow is not altered. Metabolites were assayed in small tissue samples collected either by cryoprobe biopsy in the regions where LCBFs were measured (series 1) or by sampling appropriate regions of the rapidly frozen brain (series 2). Subsequent topographical study of brain tissue pH with umbelliferone was performed in this latter series. The results from these two series are compared and discussed in terms of the more appropriate way to perform simultaneous electrode measurements and analysis of tissue samples for studying focal ischaemia in the primate brain. They confirm that the concentrations of ATP and PCr decrease, and that lactate level increases, with decreasing blood flow. These metabolites tended to change more rapidly below a blood flow threshold, rather than showing a steady decrease as the blood flow was reduced, although the variability of the data precluded us from establishing this with confidence. Topographical study of tissue pH often showed sharp boundaries between zones of very low pH and regions with normal pH.

scholarly journals Stage 1 Registered Report: Effect of deficient phagocytosis on neuronal survival and neurological outcome after temporary middle cerebral artery occlusion (tMCAo)

F1000Research ◽  
2017 ◽  
Vol 6 ◽  
pp. 1827 ◽  
Author(s):  
Julius V. Emmrich ◽  
Jonas J. Neher ◽  
Philipp Boehm-Sturm ◽  
Matthias Endres ◽  
Ulrich Dirnagl ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Middle Cerebral Artery ◽  
Middle Cerebral Artery Occlusion ◽  
Cerebral Artery ◽  
Neuronal Death ◽  
Neuronal Survival ◽  
Artery Occlusion ◽  
Neurological Recovery ◽  
Ischemic Brain ◽  
Cerebral Artery Occlusion

Stroke is a major cause of death and disability worldwide. In addition to neuronal death resulting directly from energy depletion due to lack of blood supply, inflammation and microglial activation following ischemic brain injury has been increasingly recognized to be a key contributor to the pathophysiology of cerebrovascular disease. However, our understanding of the cross talk between the ischemic brain and the immune system is limited. Recently, we demonstrated that following focal ischemia, death of mature viable neurons can be executed through phagocytosis by microglial cells or recruited macrophages, i.e. through phagoptosis. It was shown that inhibition of phagocytic signaling pathways following endothelin-1 induced focal cerebral ischemia leads to increased neuronal survival and neurological recovery. This suggests that inhibition of specific phagocytic pathways may prevent neuronal death during cerebral ischemia. To further explore this potential therapeutic target, we propose to assess the role of phagocytosis in an established model of temporary (45min) middle cerebral artery occlusion, and to evaluate neuronal survival and neurological recovery in mice with deficient phagocytosis.

Ischemic Brain Tissue Water Content: CT Monitoring during Middle Cerebral Artery Occlusion and Reperfusion in Rats1

Radiology ◽  
2007 ◽  
Vol 243 (3) ◽  
pp. 720-726 ◽  
Author(s):  
Imanuel Dzialowski ◽  
Ernst Klotz ◽  
Sophia Goericke ◽  
Arnd Doerfler ◽  
Michael Forsting ◽  
...  
Keyword(s):  
Middle Cerebral Artery ◽  
Water Content ◽  
Middle Cerebral Artery Occlusion ◽  
Brain Tissue ◽  
Artery Occlusion ◽  
Tissue Water Content ◽  
Tissue Water ◽  
Ischemic Brain ◽  
Ischemic Brain Tissue ◽  
Cerebral Artery Occlusion
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