Browsing by Author "Chaparro, Rafael E"

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    Hippocampal cellular loss after brief hypotension.
    (SpringerPlus, 2013-12) Chaparro, Rafael E; Quiroga, Carolina; Bosco, Gerardo; Erasso, Diana; Rubini, Alessandro; Mangar, Devanand; Parmagnani, Andrea; Camporesi, Enrico M
    Brief episodes of hypotension have been shown to cause acute brain damage in animal models. We used a rat hemorrhagic shock model to assess functional outcome and to measure the relative neuronal damage at 1, 4 and 14 days post-injury (3 min of hypotension). All rats underwent a neurological assessment including motor abilities, sensory system evaluation and retrograde memory at post-hypotensive insult. Brains were harvested and stained for Fluorojade C and Nissl. Stereology was used to analyze Fluorojade C and Nissl stained brain sections to quantitatively detect neuronal damage after the hypotensive insult. Statistical analysis was performed using Graphpad Prism 5 with the Bonferroni test at a 95% confidence interval after ANOVA. A Mixed Effect Model was used for the passive avoidance evaluation. Stereologically counted fluorojade positive cells in the hippocampus revealed significant differences in neuronal cell injury between control rats and rats that received 3 min of hypotension one day after insult. Quantification of Nissl positive neuronal cells showed a significant decrease in the number hippocampal cells at day 14. No changes in frontal cortical cells were evident at any time, no significative changes in neurological assessments as well. Our observations show that brief periods of hemorrhage-induced hypotension actually result in neuronal cell damage in Sprague-Dawley rats even if the extent of neuronal damage that was incurred was not significant enough to cause changes in motor or sensory behavior.
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    Sustained functional improvement by hepatocyte growth factor-like small molecule BB3 after focal cerebral ischemia in rats and mice.
    (Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism, 2015-06) Chaparro, Rafael E; Izutsu, Miwa; Sasaki, Toshihiro; Sheng, Huaxin; Zheng, Yi; Sadeghian, Homa; Qin, Tao; von Bornstadt, Daniel; Herisson, Fanny; Duan, Bin; Li, Jing-Song; Jiang, Kai; Pearlstein, Molly; Pearlstein, Robert D; Smith, David E; Goldberg, Itzhak D; Ayata, Cenk; Warner, David S
    Hepatocyte growth factor (HGF), efficacious in preclinical models of acute central nervous system injury, is burdened by administration of full-length proteins. A multiinstitutional consortium investigated the efficacy of BB3, a small molecule with HGF-like activity that crosses the blood-brain barrier in rodent focal ischemic stroke using Stroke Therapy Academic Industry Roundtable (STAIR) and Good Laboratory Practice guidelines. In rats, BB3, begun 6 hours after temporary middle cerebral artery occlusion (tMCAO) reperfusion, or permanent middle cerebral artery occlusion (pMCAO) onset, and continued for 14 days consistently improved long-term neurologic function independent of sex, age, or laboratory. BB3 had little effect on cerebral infarct size and no effect on blood pressure. BB3 increased HGF receptor c-Met phosphorylation and synaptophysin expression in penumbral tissue consistent with a neurorestorative mechanism from HGF-like activity. In mouse tMCAO, BB3 starting 10 minutes after reperfusion and continued for 14 days improved neurologic function that persisted for 8 weeks in some, but not all measures. Study in animals with comorbidities and those exposed to common stroke drugs are the next steps to complete preclinical assessment. These data, generated in independent, masked, and rigorously controlled settings, are the first to suggest that the HGF pathway can potentially be harnessed by BB3 for neurologic benefit after ischemic stroke.
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    Video training and certification program improves reliability of postischemic neurologic deficit measurement in the rat.
    (Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism, 2016-12) Taninishi, Hideki; Pearlstein, Molly; Sheng, Huaxin; Izutsu, Miwa; Chaparro, Rafael E; Goldstein, Larry B; Warner, David S
    Scoring systems are used to measure behavioral deficits in stroke research. Video-assisted training is used to standardize stroke-related neurologic deficit scoring in humans. We hypothesized that a video-assisted training and certification program can improve inter-rater reliability in assessing neurologic function after middle cerebral artery occlusion in rats. Three expert raters scored neurologic deficits in post-middle cerebral artery occlusion rats using three published systems having different complexity levels (3, 18, or 48 points). The system having the highest point estimate for the correlation between neurologic score and infarct size was selected to create a video-assisted training and certification program. Eight trainee raters completed the video-assisted training and certification program. Inter-rater agreement ( Κ: score) and agreement with expert consensus scores were measured before and after video-assisted training and certification program completion. The 48-point system correlated best with infarct size. Video-assisted training and certification improved agreement with expert consensus scores (pretraining = 65 ± 10, posttraining = 87 ± 14, 112 possible scores, P < 0.0001), median number of trainee raters with scores within ±2 points of the expert consensus score (pretraining = 4, posttraining = 6.5, P < 0.01), categories with Κ:  > 0.4 (pretraining = 4, posttraining = 9), and number of categories with an improvement in the Κ: score from pretraining to posttraining (n = 6). Video-assisted training and certification improved trainee inter-rater reliability and agreement with expert consensus behavioral scores in rats after middle cerebral artery occlusion. Video-assisted training and certification may be useful in multilaboratory preclinical studies.