Mildronate treatment improves functional recovery following middle cerebral artery occlusion in rats

2011 ◽  
Vol 222 (1) ◽  
pp. 26-32 ◽  
Author(s):  
Baiba Svalbe ◽  
Liga Zvejniece ◽  
Edijs Vavers ◽  
Osvalds Pugovics ◽  
Ruta Muceniece ◽  
...  
Keyword(s):  
Middle Cerebral Artery ◽  
Middle Cerebral Artery Occlusion ◽  
Cerebral Artery ◽  
Functional Recovery ◽  
Artery Occlusion ◽  
Cerebral Artery Occlusion

scholarly journals Brain Cleanup as a Potential Target for Poststroke Recovery

Stroke ◽  
2020 ◽  
Vol 51 (3) ◽  
pp. 958-966 ◽  
Author(s):  
Shun-Ming Ting ◽  
Xiurong Zhao ◽  
Guanghua Sun ◽  
Lidiya Obertas ◽  
Mercedes Ricote ◽  
...  
Keyword(s):  
Middle Cerebral Artery ◽  
Middle Cerebral Artery Occlusion ◽  
Cerebral Artery ◽  
Functional Recovery ◽  
Artery Occlusion ◽  
Therapeutic Window ◽  
Peroxisome Proliferator ◽  
Phagocytic Cells ◽  
Peroxisome Proliferator Activated Receptor ◽  
Cerebral Artery Occlusion

Background and Purpose— Phagocytic cells, such as microglia and blood-derived macrophages, are a key biological modality responsible for phagocytosis-mediated clearance of damaged, dead, or displaced cells that are compromised during senescence or pathological processes, including after stroke. This process of clearance is essential to eliminate the source of inflammation and to allow for optimal brain repair and functional recovery. Transcription factor, RXR (retinoic-X-receptor) is strongly implicated in phagocytic functions regulation, and as such could represent a novel target for brain recovery after stroke. Methods— Primary cultured microglia and bone marrow macrophages were used for phagocytic study. Mice with deleted RXR-α in myeloid phagocytes (Mac-RXR-α −/− ) were subjected to transient middle cerebral artery occlusion to mimic ischemic stroke and then treated with RXR agonist bexarotene. RNA-sequencing and long-term recovery were evaluated. Results— Using cultured microglia, we demonstrated that the RXR-α promotes the phagocytic functions of microglia toward apoptotic neurons. Using mice with deleted RXR-α in myeloid phagocytes (Mac-RXR-α −/− ), we have shown that despite behaving similarly to the control at early time points (up to 3 days, damage established histologically and behaviorally), these Mac-RXR-α −/− mice demonstrated worsened late functional recovery and developed brain atrophy that was larger in size than that seen in control mice. The RXR-α deficiency was associated with reduced expression of genes known to be under control of the prominent transcriptional RXR partner, PPAR (peroxisome proliferator-activated receptor)-γ, as well as genes encoding for scavenger receptors and genes that signify microglia/macrophages polarization to a reparative phenotype. Finally, we demonstrated that the RXR agonist, bexarotene, administered as late as 1 day after middle cerebral artery occlusion, improved neurological recovery, and reduced the atrophy volume as assessed 28 days after stroke. Bexarotene did not improve outcome in Mac-RXR-α −/− mice. Conclusions— Altogether, these data suggest that phagocytic cells control poststroke recovery and that RXR in these cells represents an attractive target with exceptionally long therapeutic window.

scholarly journals Delayed Recanalization Promotes Functional Recovery in Rats Following Permanent Middle Cerebral Artery Occlusion

2018 ◽  
Vol 9 (2) ◽  
pp. 185-198 ◽  
Author(s):  
Devin William McBride ◽  
Guangyong Wu ◽  
Derek Nowrangi ◽  
Jerry J. Flores ◽  
Liang Hui ◽  
...  
Keyword(s):  
Middle Cerebral Artery ◽  
Middle Cerebral Artery Occlusion ◽  
Cerebral Artery ◽  
Functional Recovery ◽  
Artery Occlusion ◽  
Cerebral Artery Occlusion

scholarly journals Intranasal Administration of PACAP Is an Efficient Delivery Route to Reduce Infarct Volume and Promote Functional Recovery After Transient and Permanent Middle Cerebral Artery Occlusion

2021 ◽  
Vol 11 ◽  
Author(s):  
Asma Cherait ◽  
Julie Maucotel ◽  
Benjamin Lefranc ◽  
Jérôme Leprince ◽  
David Vaudry
Keyword(s):  
Middle Cerebral Artery ◽  
Middle Cerebral Artery Occlusion ◽  
Cerebral Artery ◽  
Functional Recovery ◽  
Infarct Volume ◽  
Neuroprotective Effect ◽  
Systemic Exposure ◽  
Artery Occlusion ◽  
Bioactive Molecules ◽  
Cerebral Artery Occlusion

Intranasal (IN) administration appears to be a suitable route for clinical use as it allows direct delivery of bioactive molecules to the central nervous system, reducing systemic exposure and sides effects. Nevertheless, only some molecules can be transported to the brain from the nasal cavity. This led us to compare the efficiency of an IN, intravenous (IV), and intraperitoneal (IP) administration of pituitary adenylate cyclase-activating polypeptide (PACAP) after transient or permanent middle cerebral artery occlusion (MCAO) in C57BL/6 mice. The results show that the neuroprotective effect of PACAP is much more efficient after IN administration than IV injection while IP injection had no effect. IN administration of PACAP reduced the infarct volume when injected within 6 h after the reperfusion and improved functional recovery up to at least 1 week after the ischemia.

Expression of neurocan after transient middle cerebral artery occlusion in adult rat brain

2005 ◽  
Vol 25 (1_suppl) ◽  
pp. S217-S217
Author(s):  
Kentaro Deguchi ◽  
Mikiro Takaishi ◽  
Takeshi Hayashi ◽  
Atsuhiko Oohira ◽  
Shoko Nagotani ◽  
...  
Keyword(s):  
Middle Cerebral Artery ◽  
Rat Brain ◽  
Middle Cerebral Artery Occlusion ◽  
Cerebral Artery ◽  
Artery Occlusion ◽  
Adult Rat ◽  
Adult Rat Brain ◽  
Cerebral Artery Occlusion
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