Article
Social interaction improves experimental stroke outcome.
Department of Psychology, The Ohio State University, Columbus, OH 43210, USA.
Stroke (impact factor:
5.73).
10/2005;
36(9):2006-11.
DOI:10.1161/01.STR.0000177538.17687.54
Source: PubMed
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Citations (0)
- Cited In (2)
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Article: Intranasal administration of a PARG inhibitor profoundly decreases ischemic brain injury.
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ABSTRACT: Cumulative evidence has indicated a critical role of poly(ADP-ribose) polymerase-1 activation in ischemic brain damage. Poly(ADP-ribose) glycohydrolase (PARG) is a key enzyme in poly(ADP-ribose) catabolism. Our previous studies showed that PARG inhibitors, gallotannin (GT) and nobotanin B, can profoundly decrease oxidative cell death in vitro. Here, we tested the hypothesis that intranasal delivery of GT can decrease ischemic brain damage by inhibiting PARG. Intranasal delivery of 25 mg / kg GT within 5 hours after a 2-hour focal brain ischemia markedly decreased the infarct formation and neurological deficits of rats. The GT administration also increased poly(ADP-ribose) in the ischemic brains, suggesting that GT acts as a PARG inhibitor in vivo. Furthermore, the GT treatment abolished nuclear translocation of apoptosis-inducing factor (AIF) in the ischemic brains, suggesting that prevention of AIF translocation may contribute to the protective effects of GT. In contrast, intravenous injection of GT, at 2 hours after ischemic onset, did not reduce ischemic brain damage. Collectively, our findings suggest that PARG inhibition can significantly decrease ischemic brain injury, possibly by blocking AIF translocation. This study also highlights distinct merits of intranasal drug delivery for treating CNS diseases.Frontiers in Bioscience 02/2007; 12:4986-96. · 3.52 Impact Factor -
Article: Intranasal administration with NAD+ profoundly decreases brain injury in a rat model of transient focal ischemia.
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ABSTRACT: Excessive poly(ADP-ribose) polymerase-1 (PARP-1) activation plays a significant role in ischemic brain damage. Increasing evidence has supported the hypothesis that PARP-1 induces cell death by depleting intracellular NAD+. Based on our in vitro finding that NAD+ treatment can abolish PARP-1-mediated cell death, we hypothesized that NAD+ administration may decrease ischemic brain injury. In this study, we used a rat model of transient focal ischemia to test this hypothesis. We observed that intranasal NAD+ delivery significantly increased NAD+ contents in the brains. Intranasal delivery with 10 mg/kg NAD+ at 2 hours after ischemic onset profoundly decreased infarct formation when assessed either at 24 or 72 hours after ischemia. The NAD+ administration also significantly attenuated ischemia-induced neurological deficits. In contrast, intranasal administration with 10 mg/kg nicotinamide did not decrease ischemic brain damage. These results provide the first in vivo evidence that NAD+ metabolism is a new target for treating brain ischemia, and that NAD+ administration may be a novel strategy for decreasing brain damage in cerebral ischemia and possibly other PARP-1-associated neurological diseases.Frontiers in Bioscience 02/2007; 12:2728-34. · 3.52 Impact Factor
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Keywords
60-minute MCAO males
90-minute MCAO females
affiliative social interactions
behavioral assays
Behavioral assessments
behavioral outcome
contralateral paw use
decreases ischemic damage
female C57BL/6 mice
female mice
intraischemic CRP concentration
ischemic outcomes
ovariectomized female
pair housing
pair-housed males
peri-ischemic period
profound effect
significant effect
Social interaction
transient intraluminal middle cerebral artery occlusion