Neurogenic inflammation is associated with development of edema and functional deficits following traumatic brain injury in rats.
The present study has used capsaicin-induced neuropeptide depletion to examine the role of neurogenic inflammation in the development of edema and functional deficits following traumatic brain injury (TBI). Adult, male rats were treated with capsaicin (neuropeptide-depleted) or equal volume vehicle (controls) 14 days prior to induction of moderate/severe diffuse TBI. Injury in vehicle treated control animals resulted in acute (4-5 h) edema formation, which was confirmed as being vasogenic in origin by diffusion weighted magnetic resonance imaging and the presence of increased permeability of the blood-brain barrier (BBB) to Evans blue dye. There was also a significant decline in brain magnesium concentration, as assessed by phosphorus magnetic resonance spectroscopy, and the development of profound motor and cognitive deficits. In contrast, capsaicin pre-treatment resulted in a significant reduction in post-traumatic edema formation (p < 0.001), BBB permeability (p < 0.001), free magnesium decline (p < 0.01) and both motor and cognitive deficits (p < 0.001). We conclude that neurogenic inflammation may play an integral role in the development of edema and functional deficits following TBI, and that neuropeptides may be a novel target for development of interventional pharmacological strategies.
School of Pharmacy and Molecular Sciences, James Cook University, Townsville, Qld., Australia.
A J
AJ
Nimmo
I
I
Cernak
D L
DL
Heath
X
X
Hu
C J
CJ
Bennett
R
R
Vink
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects; D001834:Body Water / Q000378:metabolism; D001923:Brain Chemistry / Q000502:physiology; D001929:Brain Edema / Q000209:etiology / Q000473:pathology*; D001930:Brain Injuries / Q000150:complications / Q000473:pathology* / Q000503:physiopathology*; D001931:Brain Mapping; D002211:Capsaicin / Q000494:pharmacology; D003072:Cognition Disorders / Q000209:etiology*; D004058:Diffusion; D004660:Encephalitis / Q000209:etiology / Q000473:pathology*; D008279:Magnetic Resonance Imaging; D008297:Male; D009069:Movement Disorders / Q000209:etiology*; D009479:Neuropeptides / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology; D004856:Postural Balance / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley
D009479:Neuropeptides; D000255:Adenosine Triphosphate; D002211:Capsaicin