title: Early Recruitment of Cerebral Microcirculation by Neuronal Nitric Oxide Synthase Inhibition in a Juvenile Ischemic Rat Model.
abstract: BACKGROUND
  The development of collateral circulation is proposed as an inherent compensatory mechanism to restore impaired blood perfusion after ischemia, at least in the penumbra. We have studied the dynamic macro- and microcirculation after ischemia-reperfusion in the juvenile rat brain and evaluated the impact of neuronal nitric oxide synthase (nNOS) inhibition on the collateral flow.
  
  
  METHODS
  Fourteen-day-old (P14) rats were subjected to ischemia-reperfusion and treated with either PBS or 7-nitroindazole (7-NI, an nNOS inhibitor, 25 mg/kg). Arterial blood flow (BF) was measured using 2D-color-coded pulsed ultrasound imaging. Laser speckle contrast (LSC) imaging and sidestream dark-field videomicroscopy were used to measure cortical and microvascular BF, respectively.
  
  
  RESULTS
  In basal conditions, 7-NI reduced BF in the internal carotids (by ∼ 25%) and cortical (by ∼ 30%) BF, as compared to PBS. During ischemia, the increased mean BF velocity in the basilar trunk after both PBS and 7-NI demonstrated the establishment of collateral support and patency. Upon re-flow, BF immediately recovered to basal values in the internal carotid arteries under both conditions. The 7-NI group showed increased collateral flow in the penumbral tissue during early re-flow compared to PBS, as shown with both LSC imaging and side-stream dark-field videomicroscopy. The proportion of perfused capillaries was significantly increased under 7-NI as compared to PBS when given before ischemia (67.0 ± 3.9 vs. 46.8 ± 8.8, p < 0.01). Perfused capillaries (63.1 ± 17.7 vs. 81.1 ± 20.7, p < 0.001) and the BF index (2.4 ± 0.6 vs. 1.3 ± 0.1, p < 0.001) significantly increased under 7-NI given at the re-flow onset.
  
  
  CONCLUSIONS
  Collateral support in the penumbra is initiated during ischemia, and may be increased during early re-flow by neuronal NOS inhibition (given in pre- and post-treatment), which may preserve brain tissue in juvenile rats.
authors.affiliation: Universitx00E9; Paris Diderot, Sorbonne Paris Citx00E9;, INSERM UMR 1141, Paris, France.
authors.forename: P L
authors.initials: PL
authors.lastname: Leger
authors.forename: P
authors.initials: P
authors.lastname: Bonnin
authors.forename: R
authors.initials: R
authors.lastname: Moretti
authors.forename: S
authors.initials: S
authors.lastname: Tanaka
authors.forename: J
authors.initials: J
authors.lastname: Duranteau
authors.forename: S
authors.initials: S
authors.lastname: Renolleau
authors.forename: O
authors.initials: O
authors.lastname: Baud
authors.forename: C
authors.initials: C
authors.lastname: Charriaut-Marlangue
mesh_terms: D000818:Animals; D001783:Blood Flow Velocity / Q000187:drug effects; D001921:Brain / Q000098:blood supply / Q000187:drug effects*; D002545:Brain Ischemia; D002533:Cerebral Angiography; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D003097:Collateral Circulation / Q000187:drug effects*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006439:Hemodynamics / Q000187:drug effects*; D007191:Indazoles / Q000494:pharmacology*; D008833:Microcirculation / Q000187:drug effects*; D052248:Nitric Oxide Synthase Type I / Q000037:antagonists & inhibitors*; D051381:Rats; D015424:Reperfusion
chemical_list: D004791:Enzyme Inhibitors; D007191:Indazoles; D052248:Nitric Oxide Synthase Type I; C496322:Nos1 protein, rat; C080122:7-nitroindazole