Use of Diffusion-Weighted MRI and Neurological Deficit Scores to Demonstrate Beneficial Effects of Isradipine in a Rat Model of Focal Ischemia

Pharmacology ◽  
1999 ◽  
Vol 58 (6) ◽  
pp. 292-299 ◽  
Author(s):  
Sudeep Chandra ◽  
Ray F. White ◽  
Daryl Everding ◽  
Giora Z. Feuerstein ◽  
Robert W. Coatney ◽  
...  
2016 ◽  
Vol 19 (4) ◽  
pp. 540-549 ◽  
Author(s):  
Sandra Heskamp ◽  
Linda Heijmen ◽  
Danny Gerrits ◽  
Janneke D. M. Molkenboer-Kuenen ◽  
Edwin G. W. ter Voert ◽  
...  

2011 ◽  
Vol 31 (12) ◽  
pp. 2363-2374 ◽  
Author(s):  
Yi-Je Chen ◽  
Girija Raman ◽  
Silke Bodendiek ◽  
Martha E O'Donnell ◽  
Heike Wulff

Microglia and brain infiltrating macrophages significantly contribute to the secondary inflammatory damage in the wake of ischemic stroke. Here, we investigated whether inhibition of KCa3.1 (IKCa1/KCNN4), a calcium-activated K+ channel that is involved in microglia and macrophage activation and expression of which increases on microglia in the infarcted area, has beneficial effects in a rat model of ischemic stroke. Using an HPLC/MS assay, we first confirmed that our small molecule KCa3.1 blocker TRAM-34 effectively penetrates into the brain and achieves micromolar plasma and brain concentrations after intraperitoneal injection. Then, we subjected male Wistar rats to 90 minutes of middle cerebral artery occlusion (MCAO) and administered either vehicle or TRAM-34 (10 or 40 mg/kg intraperitoneally twice daily) for 7 days starting 12 hours after reperfusion. Both compound doses reduced infarct area by ∼50% as determined by hematoxylin & eosin staining on day 7 and the higher dose also significantly improved neurological deficit. We further observed a significant reduction in ED1+-activated microglia and TUNEL-positive neurons as well as increases in NeuN+ neurons in the infarcted hemisphere. Our findings suggest that KCa3.1 blockade constitutes an attractive approach for the treatment of ischemic stroke because it is still effective when initiated 12 hours after the insult.


2015 ◽  
Vol 42 (4) ◽  
pp. 990-998 ◽  
Author(s):  
Peter Boor ◽  
Michael Perkuhn ◽  
Martin Weibrecht ◽  
Stephanie Zok ◽  
Ina V. Martin ◽  
...  

1994 ◽  
Vol 7 (1-2) ◽  
pp. 96-100 ◽  
Author(s):  
H. B. Verheul ◽  
R. Balazs ◽  
J. W. Berkelbach van der Sprenkel ◽  
C. A. F. Tulleken ◽  
K. Nicolay ◽  
...  

2015 ◽  
Vol 35 (10) ◽  
pp. 1601-1609 ◽  
Author(s):  
Evelyn MR Lake ◽  
Joydeep Chaudhuri ◽  
Lynsie Thomason ◽  
Rafal Janik ◽  
Milan Ganguly ◽  
...  

To aid in development of chronic stage treatments for sensorimotor deficits induced by ischemic stroke, we investigated the effects of GABA antagonism on brain structure and fine skilled reaching in a rat model of focal ischemia induced via cortical microinjections of endothelin-1 (ET-1). Beginning 7 days after stroke, animals were administered a gamma-aminobutyric acid (GABAA) inverse agonist, L-655,708, at a dose low enough to afford α5-GABAA receptor specificity. A week after stroke, the ischemic lesion comprised a small hypointense necrotic core (6 ± 1 mm3) surrounded by a large (62 ± 11 mm3) hyperintense perilesional region; the skilled reaching ability on the Montoya staircase test was decreased to 34% ± 2% of the animals' prestroke performance level. On L-655,708 treatment, animals showed a progressive decrease in total stroke volume (13 ± 4 mm3 per week), with no change in animals receiving placebo. Concomitantly, treated animals' skilled reaching progressively improved by 9% ± 1% per week, so that after 2 weeks of treatment, these animals performed at 65% ± 6% of their baseline ability, which was 25% ± 11% better than animals given placebo. These data indicate beneficial effects of delayed, sustained low-dose GABAA antagonism on neuroanatomic injury and skilled reaching in the chronic stage of stroke recovery in an ET-1 rat model of focal ischemia.


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