Substance P is associated with the development of brain edema and functional deficits after traumatic brain injury.
Brain edema and swelling is a critical factor in the high mortality and morbidity associated with traumatic brain injury (TBI). Despite this, the mechanisms associated with its development are poorly understood and interventions have not changed in over 30 years. Although neuropeptides and neurogenic inflammation have been implicated in peripheral edema formation, their role in the development of central nervous system edema after brain trauma has not been investigated. This study examines the role of the neuropeptide, substance P (SP), in the development of edema and functional deficits after brain trauma in rats. After severe diffuse TBI in adult male rats, neuronal and perivascular SP immunoreactivity were increased markedly. Perivascular SP colocalized with exogenously administered Evans blue, supporting a role for SP in vascular permeability. Inhibition of SP action by administration of the neurokinin-1 (NK1) antagonist, N-acetyl-L-tryptophan, at 30 mins after trauma attenuated vascular permeability and edema formation. Administration of the NK1 antagonist also improved both motor and cognitive neurologic outcomes. These findings suggest that SP release is integrally linked to the increased vascular permeability and edema formation after brain trauma, and that treatment with an NK1 receptor antagonist reduces edema and improves neurologic outcome.
Donkin
James J
JJ
Discipline of Pathology, University of Adelaide, Adelaide, South Australia, Australia.
Nimmo
Alan J
AJ
Cernak
Ibolja
I
Blumbergs
Peter C
PC
Vink
Robert
R
D000818:Animals; D001929:Brain Edema / Q000209:etiology* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control; D001930:Brain Injuries / Q000150:complications* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D002199:Capillary Permeability / Q000187:drug effects; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D007150:Immunohistochemistry; D008279:Magnetic Resonance Imaging; D008297:Male; D018613:Microscopy, Confocal; D016253:Microscopy, Immunoelectron; D009043:Motor Activity / Q000187:drug effects*; D064729:Neurokinin-1 Receptor Antagonists; D051381:Rats; D017207:Rats, Sprague-Dawley; D013373:Substance P / Q000378:metabolism*; D014364:Tryptophan / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use
D064729:Neurokinin-1 Receptor Antagonists; D013373:Substance P; C006392:N-acetyltryptophan; D014364:Tryptophan