{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,6]],"date-time":"2026-09-06T02:00:40Z","timestamp":1788660040851,"version":"build-2803163510"},"reference-count":44,"publisher":"Journal of Neurosurgery Publishing Group (JNSPG)","issue":"4","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JNS"],"published-print":{"date-parts":[[2011,4]]},"abstract":"\nObject<\/jats:title>\nThis study investigates a potential novel application of a selective cathepsin B and L inhibitor in experimental intracerebral hemorrhage (ICH) in rats.<\/jats:p><\/jats:sec>\n\nMethods<\/jats:title>\nForty adult male Wistar rats received an ICH by stereotactic injection of 100 \u03bcl of autologous blood or sham via needle insertion into the right striatum. The rats were treated with a selective cathepsin B and L inhibitor (CP-1) or 1% dimethyl sulfoxide sterile saline intravenously at 2 and 4 hours after injury. Modified neurological severity scores were obtained and corner turn tests were performed at 1, 4, 7, and 14 days after ICH. The rats were sacrificed at 3 and 14 days after ICH for immunohistological analysis of tissue loss, neurogenesis, angiogenesis, and apoptosis.<\/jats:p><\/jats:sec>\n\nResults<\/jats:title>\nThe animals treated with CP-1 demonstrated significantly reduced apoptosis as well as tissue loss compared with controls (p < 0.05 for each). Neurological function as assessed by modified neurological severity score and corner turn tests showed improvement after CP-1 treatment at 7 and 14 days (p < 0.05). Angiogenesis and neurogenesis parameters demonstrated improvement after CP-1 treatment compared with controls (p < 0.05) at 14 days.<\/jats:p><\/jats:sec>\n\nConclusions<\/jats:title>\nThis study is the first report of treatment of ICH with a selective cathepsin B and L inhibitor. Cathepsin B and L inhibition has been shown to be beneficial after cerebral ischemia, likely because of its upstream regulation of the other prominent cysteine proteases, calpains, and caspases. While ICH may not induce a major component of ischemia, the cellular stress in the border zone may activate these proteolytic pathways. The observation that cathepsin B and L blockade is efficacious in this model is provocative for further investigation.<\/jats:p><\/jats:sec>","DOI":"10.3171\/2010.6.jns091856","type":"journal-article","created":{"date-parts":[[2010,7,30]],"date-time":"2010-07-30T13:19:54Z","timestamp":1280495994000},"page":"1110-1116","source":"Crossref","is-referenced-by-count":18,"title":["Improvement in recovery after experimental intracerebral hemorrhage using a selective cathepsin B and L inhibitor"],"prefix":"10.3171","volume":"114","author":[{"given":"Dongmei","family":"Yang","sequence":"first","affiliation":[{"name":"Departments of Neurosurgery and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuxia","family":"Han","sequence":"additional","affiliation":[{"name":"Departments of Neurosurgery and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianfeng","family":"Zhang","sequence":"additional","affiliation":[{"name":"Departments of Neurosurgery and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher","family":"Ding","sequence":"additional","affiliation":[{"name":"Departments of Neurosurgery and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Anagli","sequence":"additional","affiliation":[{"name":"Pathology, and"},{"name":"Proteomics Core Facility, Henry Ford Hospital, Detroit, Michigan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donald M.","family":"Seyfried","sequence":"additional","affiliation":[{"name":"Departments of Neurosurgery and"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1754","reference":[{"key":"b1-jns091856","series-title":"Biochem Biophys Res Commun","first-page":"86","article-title":"Effects of cathepsins B and L inhibition on postischemic protein alterations in the brain","volume":"366","author":"Anagli","year":"2008"},{"key":"b2-jns091856","series-title":"Biochem J","first-page":"93","article-title":"Affinity labelling of the Ca(2+)-activated neutral proteinase (calpain) in intact human platelets","volume":"289","author":"Anagli","year":"1993"},{"key":"b3-jns091856","series-title":"Biochem J","first-page":"497","article-title":"Investigation of the role of calpain as a stimulus-response mediator in human platelets using new synthetic inhibitors","volume":"274","author":"Anagli","year":"1991"},{"key":"b4-jns091856","series-title":"J Med Chem","first-page":"216","article-title":"Inactivation of calpain by peptidyl fluoromethyl ketones","volume":"35","author":"Angliker","year":"1992"},{"key":"b5-jns091856","series-title":"Nat Med","first-page":"963","article-title":"Neuronal replacement from endogenous precursors in the adult brain after stroke","volume":"8","author":"Arvidsson","year":"2002"},{"key":"b6-jns091856","series-title":"J Cereb Blood Flow Metab","first-page":"1272","article-title":"Activation of proinflammatory caspases by cathepsin B in focal cerebral ischemia","volume":"24","author":"Benchoua","year":"2004"},{"key":"b7-jns091856","series-title":"Biochemistry","first-page":"2596","article-title":"The \u03b2- and \u03b3-CH2 of B27-WT's Leu11 and Ile18 side chains play a direct role in calpain inhibition","volume":"43","author":"Betts","year":"2004"},{"key":"b8-jns091856","series-title":"J Biol Chem","first-page":"7800","article-title":"Structural determinants of the calpain inhibitory activity of calpastatin peptide B27-WT","volume":"278","author":"Betts","year":"2003"},{"key":"b9-jns091856","series-title":"Circulation","first-page":"e391","article-title":"Guidelines for the management of spontaneous intracerebral hemorrhage in adults: 2007 update: a guideline from the American Heart Association\/American Stroke Association stroke council, high blood pressure research council, and the quality of care and outcomes in research interdisciplinary working group","volume":"116","author":"Broderick","year":"2007"},{"key":"b10-jns091856","series-title":"Neurol Res","first-page":"184","article-title":"Intracranial haemorrhage induced at arterial pressure in the rat. 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