title: Neuropeptide release influences brain edema formation after diffuse traumatic brain injury.
abstract: The mechanisms associated with edema formation after traumatic brain injury (TBI) have not been fully elucidated. In peripheral tissue injury, the neurogenic component of inflammation plays a significant role in increased vascular permeability and edema formation. However, few studies have examined the role of neuropeptide induced neurogenic inflammation following TBI. Adult male Sprague-Dawley rats were either left untreated, or pre-treated with capsaicin (125 mg/kg s.c.) or equal volume vehicle, and injured 14 days later using the 2-meter impact-acceleration model. Subgroups of animals were assessed for blood brain barrier (BBB) permeability (Evans Blue), brain edema (wet weight/dry weight) and functional outcome (Barnes maze and Rotarod) for up to 2 weeks post-trauma. Increased BBB permeability was present in untreated animals between 3 and 6 h after injury but not at later time-points. Edema was maximal at 5 h after trauma, declined and then significantly increased over the 5 days post-trauma. In contrast, capsaicin pre-treated, neuropeptide-depleted animals exhibited no significant increase in BBB permeability or edema compared to vehicle treated animals after injury. Notably, motor and cognitive impairments were significantly reduced in the capsaicin-pretreated animals. We conclude that neurogenic inflammation contributes to the development of edema and posttraumatic deficits after diffuse TBI.
authors.affiliation: Department of Pathology, The University of Adelaide, Adelaide, SA, Australia. Robert.Vink@adelaide.edu.au
authors.forename: R
authors.initials: R
authors.lastname: Vink
authors.forename: A
authors.initials: A
authors.lastname: Young
authors.forename: C J
authors.initials: CJ
authors.lastname: Bennett
authors.forename: X
authors.initials: X
authors.lastname: Hu
authors.forename: C O
authors.initials: CO
authors.lastname: Connor
authors.forename: I
authors.initials: I
authors.lastname: Cernak
authors.forename: A J
authors.initials: AJ
authors.lastname: Nimmo
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects; D001929:Brain Edema / Q000209:etiology*; D001930:Brain Injuries / Q000150:complications* / Q000378:metabolism* / Q000503:physiopathology; D002199:Capillary Permeability / Q000187:drug effects; D002211:Capsaicin / Q000494:pharmacology; D003071:Cognition / Q000187:drug effects; D003072:Cognition Disorders / Q000517:prevention & control; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D009069:Movement Disorders / Q000517:prevention & control; D009479:Neuropeptides / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D009479:Neuropeptides; D002211:Capsaicin