title: Repetitive intraperitoneal caspase-3 inhibitor and anesthesia reduces neuronal damage.
abstract: Caspase inhibitors are usually administered intracranially. There's very limited evidence showing that they can be used intraperitoneally, and still have a beneficial effect. We tested the hypothesis that, during focal cerebral ischemia, caspase inhibitors when used in combination with an anesthetic agent results in a significantly reduction in the neuronal damage. Male Sprague Dawley rats were randomly divided into six different groups: control, Isoflurane, Propofol, Isoflurane and Caspase-3 inhibitor intraperitoneally (IP), propofol and Caspase-3 inhibitor IP and only caspase-3 inhibitor, during post-ischemia. Neurological evaluation and histochemical analysis was assessed post-ischemia. The treatment proposed, resulted in a significant decrease in the cerebral infarction volume. Combination of treatments, and caspase-3 inhibitor alone significantly decreased the number of TUNEL and cleaved caspase-3 positive cells in the boundary area of cortical infarction. IP administration appears to reach cerebral targets similarly to intracerebral model. This combination reduces the neurological damage caused by focal cerebral ischemia.
authors.affiliation: University of South Florida, Molecular Pharmacology and Physiology , Tampa, FL , USA .
authors.forename: Eduardo
authors.initials: E
authors.lastname: Chaparro
authors.forename: Diana
authors.initials: D
authors.lastname: Erasso
authors.forename: Carolina
authors.initials: C
authors.lastname: Quiroga
authors.forename: Gerardo
authors.initials: G
authors.lastname: Bosco
authors.forename: Andrea
authors.initials: A
authors.lastname: Parmagnani
authors.forename: Alessandro
authors.initials: A
authors.lastname: Rubini
authors.forename: Devanand
authors.initials: D
authors.lastname: Mangar
authors.forename: Enrico
authors.initials: E
authors.lastname: Camporesi
mesh_terms: D000758:Anesthesia; D000818:Animals; D002545:Brain Ischemia / Q000188:drug therapy* / Q000473:pathology*; D053148:Caspase 3 / Q000378:metabolism*; D061945:Caspase Inhibitors / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D007274:Injections, Intraperitoneal; D008297:Male; D009474:Neurons / Q000187:drug effects* / Q000473:pathology; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013329:Structure-Activity Relationship
chemical_list: D061945:Caspase Inhibitors; D018696:Neuroprotective Agents; D053148:Caspase 3