Neuropeptide release influences brain edema formation after diffuse traumatic brain injury.
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.
Vink
R
R
Department of Pathology, The University of Adelaide, Adelaide, SA, Australia. Robert.Vink@adelaide.edu.au
Young
A
A
Bennett
C J
CJ
Hu
X
X
Connor
C O
CO
Cernak
I
I
Nimmo
A J
AJ
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
D009479:Neuropeptides; D002211:Capsaicin