Substance P is associated with the development of brain edema and functional deficits after traumatic brain injury

• Published in: Journal of cerebral blood flow and metabolism 2009-08, Vol.29 (8), p.1388-1398
• Main Authors: Donkin, James J, Nimmo, Alan J, Cernak, Ibolja, Blumbergs, Peter C, Vink, Robert
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; Brain Edema - etiology; Brain Edema - metabolism; Brain Edema - pathology; Brain Edema - physiopathology; Brain Edema - prevention & control; Brain Injuries - complications; Brain Injuries - metabolism; Brain Injuries - pathology; Brain Injuries - physiopathology; Capillary Permeability - drug effects; Disease Models, Animal; Enzyme-Linked Immunosorbent Assay; Immunohistochemistry; Injuries of the nervous system and the skull. Diseases due to physical agents; Magnetic Resonance Imaging; Male; Medical sciences; Microscopy, Confocal; Microscopy, Immunoelectron; Motor Activity - drug effects; Neurokinin-1 Receptor Antagonists; Neurology; Rats; Rats, Sprague-Dawley; Substance P - metabolism; Traumas. Diseases due to physical agents; Tryptophan - analogs & derivatives; Tryptophan - pharmacology; Tryptophan - therapeutic use; Vascular diseases and vascular malformations of the nervous system
• ISSN: 0271-678X; 1559-7016
• DOI: 10.1038/jcbfm.2009.63

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 (NIC,) antagonist, N-acetyl-l-tryptophan, at 30 mins after trauma attenuated vascular permeability and edema formation. Administration of the NIC, 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 NIC, receptor antagonist reduces edema and improves neurologic outcome.