Calpain inhibitor AK295 attenuates motor and cognitive deficits following experimental brain injury in the rat
| Autor: | Tracy K. McIntosh, Douglas H. Smith, Hisayuki Murai, Kathryn E. Saatman, Neil Hayward, Raymond T. Bartus, Brian R. Perri |
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| Rok vydání: | 1996 |
| Předmět: |
Male
Experimental brain injury medicine.medical_specialty Central nervous system Morris water navigation task Cysteine Proteinase Inhibitors Calcium in biology Rats Sprague-Dawley Memory Internal medicine medicine Animals Cognitive deficit Multidisciplinary biology Calpain business.industry Cognition Dipeptides Rats Cognitive test Disease Models Animal medicine.anatomical_structure Endocrinology Brain Injuries biology.protein medicine.symptom Cognition Disorders business Psychomotor Performance Research Article |
| Zdroj: | Proceedings of the National Academy of Sciences. 93:3428-3433 |
| ISSN: | 1091-6490 0027-8424 |
| DOI: | 10.1073/pnas.93.8.3428 |
| Popis: | Marked increases in intracellular calcium may play a role in mediating cellular dysfunction and death following central nervous system trauma, in part through the activation of the calcium-dependent neutral protease calpain. In this study, we evaluated the effect of the calpain inhibitor AK295 [Z-Leu-aminobutyric acid-CONH(CH2)3-morpholine] on cognitive and motor deficits following lateral fluid percussion brain injury in rats. Before injury, male Sprague-Dawley rats (350-425 g) were trained to perform a beam-walking task and to learn a cognitive test using a Morris water maze paradigm. Animals were subjected to fluid percussion injury (2.2-2.4 atm; 1 atm = 101.3 kPa) and, beginning at 15 min postinjury, received a continuous intraarterial infusion of AK295 (120-140 mg/kg, n = 15) or vehicle (n= 16) for 48 hr. Sham (uninjured) animals received either drug (n = 5) or vehicle (n = 10). Animals were evaluated for neurobehavioral motor function at 48 hr and 7 days postinjury and were tested in the Morris water maze to evaluate memory retention at 7 days postinjury. At 48 hr, both vehicle- and AK295-treated injured animals showed significant neuromotor deficits (P< 0.005). At 7 days, injured animals that received vehicle continued to exhibit significant motor dysfunction (P< 0.01). However, brain-injured, AK295-treated animals showed markedly improved motor scores (P |
| Databáze: | OpenAIRE |
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