title: Role of histamine in brain protection in surgical brain injury in mice.
abstract: Surgical resection of brain tissue is associated with tissue damage at the resection margin. Studies of ischemic brain injury in rodents have shown that administration of L-histidine and thioperamide reduces ischemic tissue loss, in part by inhibition of apoptotic cell death. In this study we tested administration of L-histidine and thioperamide in surgical brain injury in mice. Mice were randomized to one of three groups: Sham surgery (n=18), surgical brain injury without treatment (SBI) (n=33), and surgical brain injury with combined l-histidine and thioperamide treatment (SBI+H) (n=29). Surgical brain injury was induced via right frontal craniotomy with resection of the right frontal lobe. L-histidine (1000 mg/kg) and thioperamide (5 mg/kg) were administered to the SBI+H group immediately following surgical resection. Postoperative assessment included neurobehavioral scores, Evans blue measurement of blood-brain barrier breakdown, brain water content, Nissl histology, and immunohistochemistry for IgG and cleaved caspase 3. Postoperative findings included equivalent neurobehavioral outcomes at 24 and 72 h in the SBI and SBI+H groups, similar histological outcomes between SBI and SBI+H, and similar qualitative staining for cleaved caspase 3. SBI+H had increased BBB breakdown on Evans blue analysis and a trend towards increased brain edema which was significant at 72 h. We conclude that combined treatment with l-histidine and thioperamide leads to increased BBB breakdown and brain edema in surgical brain injury.
authors.affiliation: Department of Physiology and Pharmacology, Loma Linda University School of Medicine, Risley Hall, Loma Linda, CA 92350, USA.
authors.forename: Thomas P
authors.initials: TP
authors.lastname: Bravo
authors.forename: Gerald A
authors.initials: GA
authors.lastname: Matchett
authors.forename: Vikram
authors.initials: V
authors.lastname: Jadhav
authors.forename: Robert D
authors.initials: RD
authors.lastname: Martin
authors.forename: Aliiah
authors.initials: A
authors.lastname: Jourdain
authors.forename: Austin
authors.initials: A
authors.lastname: Colohan
authors.forename: John H
authors.initials: JH
authors.lastname: Zhang
authors.forename: Jiping
authors.initials: J
authors.lastname: Tang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000502:physiology; D001834:Body Water / Q000502:physiology; D001923:Brain Chemistry / Q000187:drug effects; D001930:Brain Injuries / Q000209:etiology / Q000473:pathology*; D004396:Coloring Agents; D005070:Evans Blue; D007839:Functional Laterality / Q000502:physiology; D006632:Histamine / Q000502:physiology*; D006633:Histamine Antagonists / Q000627:therapeutic use*; D006639:Histidine / Q000627:therapeutic use*; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D019635:Neurosurgical Procedures / Q000009:adverse effects*; D010812:Physical Stimulation; D010880:Piperidines / Q000627:therapeutic use*; D011183:Postoperative Complications / Q000473:pathology / Q000517:prevention & control*; D014738:Vibrissae; D016138:Walking / Q000502:physiology
chemical_list: D004396:Coloring Agents; D006633:Histamine Antagonists; D010880:Piperidines; D005070:Evans Blue; D006639:Histidine; D006632:Histamine; C052075:thioperamide