1998
DOI: 10.1161/01.str.29.1.152
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Six-Hour Window of Opportunity for Calpain Inhibition in Focal Cerebral Ischemia in Rats

Abstract: Background and Purpose-Stroke patients often experience a significant temporal delay between the onset of ischemia and the time to initiation of therapy. Thus, there is a need for neuroprotectants with a long therapeutic window of opportunity. The efficacy of a potent, central nervous system-penetrating calpain inhibitor (MDL 28,170) was evaluated in a temporary model of focal cerebral ischemia to determine the window of opportunity for intracellular protease inhibition. Methods-An ex vivo brain protease inhib… Show more

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Cited by 231 publications
(145 citation statements)
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References 42 publications
(20 reference statements)
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“…Accordingly, the participation of Cdk5 in excitotoxicity is concordant with the deregulated Ca 2ϩ , the prime effectors of excitotoxic damage. The link between excitotoxicity, calpains, and Cdk5 is strengthened by reports that calpain inhibition is also protective in focal models of stroke (32). Numerous substrates of Cdk5 have been reported.…”
Section: Discussionmentioning
confidence: 94%
“…Accordingly, the participation of Cdk5 in excitotoxicity is concordant with the deregulated Ca 2ϩ , the prime effectors of excitotoxic damage. The link between excitotoxicity, calpains, and Cdk5 is strengthened by reports that calpain inhibition is also protective in focal models of stroke (32). Numerous substrates of Cdk5 have been reported.…”
Section: Discussionmentioning
confidence: 94%
“…Inhibition of calpain I activity reduces the injury associated with ischemia reperfusion of the brain, [65][66][67] liver, 68 and heart. 69 -72 The mechanism by which inhibitors of calpain activity protect tissues/organs against reperfusion injury is not entirely clear.…”
Section: Discussionmentioning
confidence: 99%
“…Immediately after completion of the bolus, infusion of 15 mg/kg/h MDL-28170 or equivalent volume of vehicle was initiated and continued for 2.5 h. To achieve maximum calpain inhibition at time of injury, optic nerve stretch was performed 30 min after completion of the initial IV bolus (Markgraf et al, 1998;Thompson et al, 2010).…”
Section: Mdl-28170 Therapymentioning
confidence: 99%
“…Intravenous MDL-28170 has been demonstrated to penetrate into the parenchyma of uninjured brains as well as having neuroprotective properties after ischemic and traumatic brain injury (Markgraf et al, 1998;Thompson et al, 2010). The blood-optic nerve barrier is similar in structure to the blood-FIG.…”
Section: Calpain Inhibition In Tbimentioning
confidence: 99%