title: Epsilon Aminocaproic Acid Pretreatment Provides Neuroprotection Following Surgically Induced Brain Injury in a Rat Model.
abstract: Neurosurgical procedures can damage viable brain tissue unintentionally by a wide range of mechanisms. This surgically induced brain injury (SBI) can be a result of direct incision, electrocauterization, or tissue retraction. Plasmin, a serine protease that dissolves fibrin blood clots, has been shown to enhance cerebral edema and hemorrhage accumulation in the brain through disruption of the blood brain barrier. Epsilon aminocaproic acid (EAA), a recognized antifibrinolytic lysine analogue, can reduce the levels of active plasmin and, in doing so, potentially can preserve the neurovascular unit of the brain. We investigated the role of EAA as a pretreatment neuroprotective modality in a SBI rat model, hypothesizing that EAA therapy would protect brain tissue integrity, translating into preserved neurobehavioral function. Male Sprague-Dawley rats were randomly assigned to one of four groups: sham (n = 7), SBI (n = 7), SBI with low-dose EAA, 150 mg/kg (n = 7), and SBI with high-dose EAA, 450 mg/kg (n = 7). SBI was induced by partial right frontal lobe resection through a frontal craniotomy. Postoperative assessment at 24 h included neurobehavioral testing and measurement of brain water content. Results at 24 h showed both low- and high-dose EAA reduced brain water content and improved neurobehavioral function compared with the SBI groups. This suggests that EAA may be a useful pretherapeutic modality for SBI. Further studies are needed to clarify optimal therapeutic dosing and to identify mechanisms of neuroprotection in rat SBI models.
authors.affiliation: Department of Anesthesiology, Loma Linda University School of Medicine, Loma Linda, CA, USA.
authors.forename: Esther S
authors.initials: ES
authors.lastname: Komanapalli
authors.affiliation: Department of Physiology and Pharmacology, Loma Linda University School of Medicine, Loma Linda, CA, USA.
authors.forename: Prativa
authors.initials: P
authors.lastname: Sherchan
authors.affiliation: Department of Physiology and Pharmacology, Loma Linda University School of Medicine, Loma Linda, CA, USA.
authors.forename: William
authors.initials: W
authors.lastname: Rolland
authors.affiliation: Department of Anesthesiology, Loma Linda University School of Medicine, Loma Linda, CA, USA.
authors.forename: Nikan
authors.initials: N
authors.lastname: Khatibi
authors.affiliation: Department of Anesthesiology, Loma Linda University School of Medicine, Loma Linda, CA, USA.
authors.forename: Robert D
authors.initials: RD
authors.lastname: Martin
authors.affiliation: Department of Anesthesiology, Loma Linda University School of Medicine, Loma Linda, CA, USA.
authors.forename: Richard L
authors.initials: RL
authors.lastname: Applegate
authors.affiliation: Department of Physiology and Pharmacology, Loma Linda University School of Medicine, Loma Linda, CA, USA.
authors.forename: Jiping
authors.initials: J
authors.lastname: Tang
authors.affiliation: Department of Anesthesiology, Loma Linda University School of Medicine, Loma Linda, CA, USA. johnzhang3910@yahoo.com.|Department of Physiology and Pharmacology, Loma Linda University School of Medicine, Loma Linda, CA, USA. johnzhang3910@yahoo.com.|Departments of Anesthesiology, Physiology and Neurosurgery, Loma Linda University School of Medicine, 11234 Anderson Street, Room 2562B, Loma Linda, CA, 92354, USA. johnzhang3910@yahoo.com.|Department of Neurosurgery, Loma Linda University School of Medicine, Loma Linda, CA, USA. johnzhang3910@yahoo.com.
authors.forename: John H
authors.initials: JH
authors.lastname: Zhang
mesh_terms: D015119:Aminocaproic Acid / Q000494:pharmacology*; D000818:Animals; D000933:Antifibrinolytic Agents / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D001929:Brain Edema / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D001930:Brain Injuries / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D004195:Disease Models, Animal; D005625:Frontal Lobe / Q000601:surgery; D007431:Intraoperative Complications; D018696:Neuroprotective Agents / Q000494:pharmacology*; D019635:Neurosurgical Procedures; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000933:Antifibrinolytic Agents; D018696:Neuroprotective Agents; D015119:Aminocaproic Acid
keywords: Aminocaproic acid; Neurosurgery; Plasmin; Surgically induced brain injury (SBI); Tissue plasminogen activator