title: Substance P-induced changes in cell genesis following diffuse traumatic brain injury.
abstract: Inhibition of substance P (SP) activity through the use of NK1 receptor antagonists has been shown to be a promising neuroprotective therapy following traumatic brain injury (TBI). Conversely, recent research has implicated SP in the stimulation of neurogenesis, suggesting that the neuropeptide has the potential to promote recovery following TBI. This study characterised the effects of SP and the NK1 antagonist, n-acetyl tryptophan (NAT), on cell proliferation following diffuse TBI. Adult male Sprague-Dawley rats were injured using the impact acceleration model of TBI and randomly assigned to one of five treatment groups: sham, vehicle control, NAT alone, SP alone or SP with NAT. Cellular proliferation was assessed with immunostaining for bromodeoxyuridine (BrdU) and cell-specific markers. Infusion of SP (±NAT) promoted cellular proliferation in the subventricular zone and dentate gyrus following TBI. This increase was largely associated with microglial proliferation and did not correspond with functional improvements. These results suggest that NAT treatment results in neuroprotection following TBI, mediated in part via inhibition of microglia.
authors.affiliation: Adelaide Centre for Neuroscience Research, School of Medical Sciences, The University of Adelaide, SA 5000, Australia.
authors.forename: H L
authors.initials: HL
authors.lastname: Carthew
authors.forename: J M
authors.initials: JM
authors.lastname: Ziebell
authors.forename: R
authors.initials: R
authors.lastname: Vink
mesh_terms: D000818:Animals; D001930:Brain Injuries / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control*; D002454:Cell Differentiation / Q000502:physiology; D008297:Male; D017628:Microglia / Q000473:pathology / Q000502:physiology*; D055495:Neurogenesis / Q000502:physiology*; D064729:Neurokinin-1 Receptor Antagonists; D018696:Neuroprotective Agents / Q000008:administration & dosage*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D018040:Receptors, Neurokinin-1 / Q000502:physiology; D013373:Substance P / Q000008:administration & dosage*; D014364:Tryptophan / Q000031:analogs & derivatives / Q000494:pharmacology
chemical_list: D064729:Neurokinin-1 Receptor Antagonists; D018696:Neuroprotective Agents; D018040:Receptors, Neurokinin-1; D013373:Substance P; C006392:N-acetyltryptophan; D014364:Tryptophan