title: Effect of inducible nitric oxide synthase on cerebral blood flow after experimental traumatic brain injury in mice.
abstract: Inducible nitric oxide synthase (iNOS) has been suggested to play a complex role in the response to central nervous system insults such as traumatic brain injury (TBI) and cerebral ischemia. In the current study, we quantified maps of regional cerebral blood flow (CBF) using an arterial spin-labeling magnetic resonance imaging (MRI) technique, at 24 and 72 h after experimental TBI in iNOS knockout (KO) and wild-type (WT) mice. Our hypothesis was that iNOS would contribute to the level of CBF at 72 h after experimental TBI in mice. Comparing anatomical brain regions of interest (ROIs) at 24-h post controlled cortical impact (CCI), there were significant reductions in CBF in the hemisphere, cortex, and contusion-rich area of the cortex of injured animals versus naive, regardless of genotype. Regional assessment of CBF at 72 h after injury demonstrated that recovery of CBF was reduced in the ipsilateral hippocampus, thalamus, and amygdala/piriform cortex in iNOS KO versus WT mice by 26%, 15%, and 21%, respectively; this attenuated recovery was restricted to structures outside the contusion. These regions with reduced CBF in iNOS KO mice represented ROIs where CBF in the WT was either numerically or statistically greater than that seen in respective WT naive, suggesting a contribution of iNOS to delayed posttraumatic hyperemia. However, pixel analysis denoted that the contribution of iNOS to CBF at 72 h was not limited to hyperemia flows. In conclusion, iNOS plays a role in the recovery of CBF after CCI in mice. Questions remain if this effect represents a homeostatic component of CBF recovery, pathologic vasodilatation linked to inflammation, or NO-mediated facilitation of angiogenesis.
authors: Pittsburgh NMR Center for Biomedical Research, Carnegie Mellon University, Pittsburgh, Pennsylvania, USA.
authors: Lesley M
authors: LM
authors: Foley
authors: T Kevin
authors: TK
authors: Hitchens
authors: John A
authors: JA
authors: Melick
authors: Hülya
authors: H
authors: Bayir
authors: Chien
authors: C
authors: Ho
authors: Patrick M
authors: PM
authors: Kochanek
mesh_terms: D000818:Animals; D001930:Brain Injuries / Q000201:enzymology* / Q000473:pathology / Q000503:physiopathology*; D002560:Cerebrovascular Circulation / Q000502:physiology*; D004578:Electron Spin Resonance Spectroscopy; D007427:Intracranial Pressure / Q000502:physiology; D008279:Magnetic Resonance Imaging; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D052247:Nitric Oxide Synthase Type II / Q000502:physiology*; D020127:Recovery of Function / Q000502:physiology*; D013997:Time Factors
chemical_list: D052247:Nitric Oxide Synthase Type II