Abstract |
Calpains and cathepsins are two families of proteases that play an important role in ischemic cell death. In this study, we investigated the effect of E64d, a mu-calpain and cathepsin B inhibitor, in the prevention of neuronal and endothelial apoptotic cell death after focal cerebral ischemia in rats. Rats underwent 2 hr of transient focal ischemia from middle cerebral artery occlusion (MCAO) and were sacrificed 24 hr later. E64d (5 mg/ kg intraperitoneally) was administered 30 min before MCAO. Assessment included neurological function, infarction volume, brain water content, blood-brain barrier permeability, histology, and immunohistochemistry. The E64d-treated rats had significant brain protection against ischemic damage. We observed a reduction of infarction volume, brain edema, and improved neurological scores in E64d-treated rats compared with the nontreated control. Furthermore, there was a remarkable reduction in both proteases and caspase-3 activation and apoptotic changes in both neurons and endothelial cells in E64d-treated rats. These results suggest that E64d protects the brain against ischemic/ reperfusion injury by attenuating neuronal and endothelial apoptosis.
|
Authors | Tamiji Tsubokawa, Mitsuo Yamaguchi-Okada, John W Calvert, Ihsan Solaroglu, Norihito Shimamura, Kenichiro Yata, John H Zhang |
Journal | Journal of neuroscience research
(J Neurosci Res)
Vol. 84
Issue 4
Pg. 832-40
(Sep 2006)
ISSN: 0360-4012 [Print] United States |
PMID | 16802320
(Publication Type: Comparative Study, Journal Article, Research Support, N.I.H., Extramural)
|
Chemical References |
- Neuroprotective Agents
- Tetrazolium Salts
- triphenyltetrazolium
- Cathepsins
- Calpain
- Casp3 protein, rat
- Caspase 3
- Caspases
- mu-calpain
- Phosphopyruvate Hydratase
- Leucine
- aloxistatin
|
Topics |
- Analysis of Variance
- Animals
- Apoptosis
(drug effects)
- Brain Edema
(drug therapy)
- Brain Infarction
(etiology, pathology, prevention & control)
- Brain Ischemia
(etiology, prevention & control)
- Calpain
(metabolism)
- Caspase 3
- Caspases
(metabolism)
- Cathepsins
(metabolism)
- Endothelium, Vascular
(drug effects)
- Functional Laterality
(physiology)
- Gene Expression
(drug effects)
- Immunohistochemistry
(methods)
- In Situ Nick-End Labeling
(methods)
- Infarction, Middle Cerebral Artery
(complications, pathology)
- Leucine
(analogs & derivatives, therapeutic use)
- Male
- Neurologic Examination
(methods)
- Neurons
(drug effects)
- Neuroprotective Agents
(therapeutic use)
- Phosphopyruvate Hydratase
(metabolism)
- Rats
- Rats, Sprague-Dawley
- Tetrazolium Salts
|