title: Monitoring of cerebral blood flow during hypoxia-ischemia and resuscitation in the neonatal rat using laser speckle imaging.
abstract: Neonatal hypoxic-ischemic encephalopathy (HIE) is associated with alterations in cerebral blood flow (CBF) as a result of perinatal asphyxia. The extent to whichCBFchanges contribute to injury, and whether treatments that ameliorate these changes might be neuroprotective, is still unknown. Higher throughput techniques to monitorCBFchanges in rodent models ofHIEcan help elucidate the underlying pathophysiology. We developed a laser speckle imaging (LSI) technique to continuously monitorCBFin six postnatal-day 10 (P10) rats simultaneously before, during, and after unilateral hypoxia-ischemia (HI, ligation of the left carotid artery followed by hypoxia in 8% oxygen). After ligation,CBFto the ligated side fell by 30% compared to the unligated side (P < 0.0001). Hypoxia induced a bilateral 55% reduction inCBF, which was partially restored by resuscitation. Compared to resuscitation in air, resuscitation in 100% oxygen increasedCBFto the ligated side by 45% (P = 0.033). Individual variability inCBFresponse to hypoxia between animals accounted for up to 24% of the variability in hemispheric area loss to the ligated side. In both P10 and P7 models of unilateralHI, resuscitation in 100% oxygen did not affect hemispheric area loss, or hippocampalCA1 pyramidal neuron counts, after 1-week survival. ContinuousCBFmonitoring usingLSIin multiple rodents simultaneously can screen potential treatment modalities that affectCBF, and provide insight into the pathophysiology ofHI.
authors.affiliation: Department of Physiology, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway.
authors.forename: Thomas
authors.initials: T
authors.lastname: Wood
authors.affiliation: Neonatal Neuroscience, School of Clinical Sciences, University of Bristol, Bristol, United Kingdom.
authors.forename: Elisa
authors.initials: E
authors.lastname: Smit
authors.affiliation: Department of Physiology, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway.
authors.forename: Elke
authors.initials: E
authors.lastname: Maes
authors.affiliation: Department of Physiology, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway.
authors.forename: Damjan
authors.initials: D
authors.lastname: Osredkar
authors.affiliation: Department of Physiology, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway.
authors.forename: Mari
authors.initials: M
authors.lastname: Falck
authors.affiliation: Department of Physiology, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway.
authors.forename: Maja
authors.initials: M
authors.lastname: Elstad
authors.affiliation: Department of Physiology, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway Neonatal Neuroscience, School of Clinical Sciences, University of Bristol, Bristol, United Kingdom marianne.thoresen@medisin.uio.no.
authors.forename: Marianne
authors.initials: M
authors.lastname: Thoresen
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001783:Blood Flow Velocity; D056547:CA1 Region, Hippocampal / Q000098:blood supply* / Q000473:pathology; D002339:Carotid Arteries / Q000503:physiopathology / Q000601:surgery; D016923:Cell Death; D002560:Cerebrovascular Circulation; D054022:Cerebrum / Q000098:blood supply* / Q000473:pathology; D004195:Disease Models, Animal; D020925:Hypoxia-Ischemia, Brain / Q000175:diagnosis* / Q000473:pathology / Q000503:physiopathology / Q000628:therapy; D017078:Laser-Doppler Flowmetry; D008026:Ligation; D010102:Oxygen Inhalation Therapy; D017966:Pyramidal Cells / Q000473:pathology; D017208:Rats, Wistar; D012039:Regional Blood Flow; D012151:Resuscitation / Q000379:methods*; D013997:Time Factors
keywords: Cerebral blood flow; hypoxia‐ischemia; neonatal; oxygen; resuscitation