title: Combined damage produced by multiple mild cerebral insults assessed using MRI in neonatal rats.
abstract: OBJECTIVE
  To determine whether damage to neonatal brain is exacerbated with multiple mild cerebral insults as detected with MRI and corroborated using histology.
  
  
  METHODS
  The combined brain injury produced by multiple procedures was compared in neonatal rats having: Sham surgery at P5, Sham surgery at P5 plus a diffuse mild transient unilateral cerebral hypoxia ischemia (HI) at P7, HI alone, and a minor photothrombotic (PT) stroke at P5 followed by HI. MRI after the ischemic insults was followed by final histology.
  
  
  RESULTS
  PT produced lesions with increased T2and decreased apparent diffusion coefficient for water (ADC) but no significant effects of a second HI. However, near the PT lesion/parietal cortex there were patchy areas of enhanced T2and decreased ADC in 6/9, 3/8 and 0/8 animals in the PT+HI, Sham+HI and HI groups, respectively (P<0.05). Patches corresponded histologically to increased vacuolation and cell death and were more pronounced in the PT+HI and Sham+PT groups than the HI group.
  
  
  CONCLUSIONS
  The extent of damage produced by a minor neonatal stroke followed by a diffuse HI two days later results in heterogeneous enhancement of T2, ADC and histological injury near the lesion. Surgical procedures including mechanical head manipulation followed by HI also produced some enhanced heterogeneity of hypoxic-ischemic injury affirming the need for sham controls.
authors.affiliation: Department of Physiology and Pharmacology, Hotchkiss Brain Institute, Faculty of Medicine, University of Calgary, 3280 Hospital Dr, NW, Calgary, T2N 2T8, Canada. Electronic address: utuor@ucalgary.ca.
authors.forename: Ursula I
authors.initials: UI
authors.lastname: Tuor
authors.affiliation: Department of Physiology and Pharmacology, Hotchkiss Brain Institute, Faculty of Medicine, University of Calgary, 3280 Hospital Dr, NW, Calgary, T2N 2T8, Canada.
authors.forename: Manasi
authors.initials: M
authors.lastname: Sule
authors.affiliation: Department of Physiology and Pharmacology, Hotchkiss Brain Institute, Faculty of Medicine, University of Calgary, 3280 Hospital Dr, NW, Calgary, T2N 2T8, Canada.
authors.forename: Min
authors.initials: M
authors.lastname: Qiao
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000473:pathology; D020925:Hypoxia-Ischemia, Brain / Q000150:complications / Q000473:pathology*; D020767:Intracranial Thrombosis / Q000150:complications / Q000473:pathology*; D002546:Ischemic Attack, Transient / Q000150:complications / Q000473:pathology*; D008027:Light; D008279:Magnetic Resonance Imaging; D017208:Rats, Wistar; D020521:Stroke / Q000150:complications / Q000473:pathology*
keywords: Brain injury; Hypoxia-ischemia; Magnetic resonance imaging; Neonate; Rat; Stroke