Behavioral performance of rats following neonatal hypoxia-ischemia.

Young, Robert S.; Kolonich, J.; Woods, Cynthia; Yagel, Susan K.

doi:10.1161/01.str.17.6.1313

Cited by 55 publications

(34 citation statements)

References 16 publications

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“…Previous studies have found that HI causes a number of functional deficits including slowing of various developmental milestones (eye opening, righting reflex), locomotor activity and sensorimotor and memory deficits (24,25,28,29). The present study used three different functional indices to assess behavioral deficits after HI and of these, the grip traction test which is used to assess forelimb muscle strength, appeared to be the most useful index relating to total lesion volume.…”

Section: Discussionmentioning

confidence: 77%

Long-Term Functional and Protective Actions of Preconditioning With Hypoxia, Cobalt Chloride, and Desferrioxamine Against Hypoxic-Ischemic Injury in Neonatal Rats

et al. 2008

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ABSTRACT:Preconditioning with hypoxia and hypoxia-mimetic compounds cobalt chloride (CoCl 2 ) and desferrioxamine (DFX) protects against hypoxic-ischemic (HI) injury in neonatal rat brain. We examined long-term functional and protective actions of preconditioning induced by hypoxia, CoCl 2 and DFX in a neonatal rat model of HI. Postnatal day six rat pups were exposed to preconditioning with hypoxia (8% oxygen) or injections of CoCl 2 , DFX or saline vehicle and 24 h later rats underwent HI or sham surgery. Behavioral tests were performed and at the conclusion of experiments, brains removed for morphologic analyses. HI resulted in a large unilateral lesion in the ipsilateral hemisphere compared with sham control rats. All preconditioning treatments significantly reduced the total lesion volume. Behavioral deficits were observed in HI rats compared with sham controls. The reduction in forelimb grasping strength in HI rats was attenuated by preconditioning with hypoxia, CoCl 2 and DFX. HI increased the number of foot faults in a grid-walking test and resulted in forelimb asymmetry in the cylinder test. Only preconditioning with hypoxia reversed all three functional deficits after HI. These findings indicate that preconditioning, especially when induced by hypoxia, has the potential to minimize the morphologic and functional effects of neonatal HI injury. (Pediatr Res 63: 620-624, 2008)

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Section: Discussionmentioning

confidence: 77%

Long-Term Functional and Protective Actions of Preconditioning With Hypoxia, Cobalt Chloride, and Desferrioxamine Against Hypoxic-Ischemic Injury in Neonatal Rats

et al. 2008

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“…Immediately after hypoxic exposure pups were exposed either to RA or 100% O 2 for 30 min at 25°C and then returned to their dams. Because it has been shown that carotid artery ligation without hypoxia (sham) produced neither brain damage, nor functional impairments in rodents (13,14), littermate naïve (no HI) mice were used as a control. Mice that died during hypoxia (n ϭ 8) or cannibalized (n ϭ 11) by their dams were excluded.…”

Section: Methodsmentioning

confidence: 99%

Reoxygenation with 100% Oxygen Versus Room Air: Late Neuroanatomical and Neurofunctional Outcome in Neonatal Mice with Hypoxic-Ischemic Brain Injury

et al. 2006

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Study investigated neuroutcome in mice subjected at 7-8 d of life to hypoxic-ischemic brain injury (HI) followed by 30 min of reoxygenation with 100% O 2 (Re-O 2 ) or room air (Re-Air). At 24 h of recovery, mouse reflexes were tested. At 7 wks after HI spatial orientation and memory were assessed in the same mice. Mortality rate was recorded at 24 h and at 7 wks of recovery. In separate cohort of mice, changes in cerebral blood flow (CBF) during HI-insult and reoxygenation were recorded. T he resuscitation of asphyxiated neonates is aimed to reestablish tissue oxygen delivery by restoring blood flow and increasing the arterial oxygen content. Use of 100% O 2 during neonatal resuscitation is currently recommended (1). However, Re-O 2 compared with Re-Air significantly exacerbates an oxidative stress in asphyxiated neonates (2), which is one of the mechanisms of HI-brain injury (3). To avoid hyperoxia-induced oxidative stress, the efficacy of resuscitation with room air (RA) instead of 100% O 2 is being extensively studied. To date, results of these studies are conflicting. For instance, it was reported that in asphyxiated pigs the Re-O 2 restored CBF significantly faster and more complete compared with Re-Air (4). Significantly higher levels of excitatory amino acids were found in the striatum of newborn HI-piglets Re-Air compared with Re-O 2 piglets which may be indicative of less favorable neurologic prognosis for Re-Air animals (5). However, Liu. Y and co-authors, using a canine model of cardiac arrest, demonstrated that Re-O 2 versus ReAir resulted in greater neurologic impairment assessed at 24 h of recovery (6). In contrast, the postischemic use of hyperbaric oxygenation, which produces substantial oxidative stress (7), significantly improved neurologic score following focal cerebral ischemia in adult rats and HI in neonatal rats (8,9). Hyperbaric oxygenation used as a mode of resuscitation from experimental heatstroke in rats was shown to be significantly neuroprotective (10). Meier and co-authors reported that hyperoxic ventilation significantly reduced short-term (6 h) mortality due to systemic ischemia following an acute hemorrhagic shock in pigs (11). The most recent meta-analysis indicates that there are not enough data to challenge current recommendation of using of pure O 2 during resuscitation (12).The assessment of long-term neurologic handicap following HI is of paramount clinical value to define the ultimate efficacy of Re-O2 versus Re-Air in an asphyxiated subject. There are no reports on late neurologic outcome and reoxygenation strategy following asphyxia. This work was undertaken to provide experimental data on short-and long-term neuropathological and neurofunctional outcomes in HIaffected mice re-oxygenated with either 100% O 2 or RA immediately following the index event. MATERIALS AND METHODSMurine model of HI. Three day old (p3) C57/BL6J mice of both genders were purchased from Jackson Laboratories (Bar Harbor, ME) with their birth mothers. All research was conducted according ...

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“…We refrained from evaluating an additional group of animals with carotid artery ligation only, inasmuch as it has been demonstrated that ligation neither produced brain damage (22) nor functional impairments (13,28,29). A total of 62 rats were used in the experiment.…”

Section: Methodsmentioning

confidence: 99%

Delayed Postischemic Hypothermia Improves Long-Term Behavioral Outcome after Cerebral Hypoxia-Ischemia in Neonatal Rats

2002

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Hypothermia may be an ideal neuroprotective intervention in hypoxic-ischemic encephalopathy after perinatal asphyxia. The present study describes the long-term effects of prolonged resuscitative whole-body hypothermia initiated 2 h after hypoxicischemic injury on brain morphology and neuropsychological behavior in 7-d-old rats. After right common carotid artery ligation and exposure to hypoxia of 8% O 2 for 105 min, 10 animals were kept normothermic at 37°C and 10 animals were cooled to 30°C rectal temperature for 26 h, starting 2 h after the hypoxic-ischemic insult. All hypoxic-ischemic animals were gavage fed to guarantee long-term survival. Neuroprotection was evaluated by magnetic resonance imaging and behavioral testing. Hypothermia significantly reduced the final size of cerebral infarction by 23% at 6 wk after the insult. The most extended tissue rescue was found in the hippocampus (21%, p ϭ 0.031), followed by the striatum (13%, p ϭ 0.143) and the cortex (11%, p ϭ 0.160). Cooling salvaged spatial memory deficits verified at 5 wk of recovery with Morris Water Maze test; whereas circling abnormalities after apomorphine injection and sensory motor dysfunctions on rotating treadmill improved, yet did not reach statistical significance. When compared with controls, hypoxicischemic animals performed worse in all behavioral tests. Hypothermia did not influence functional outcome in controls. Significant correlations between behavioral performance and corresponding regional brain volumes were found. We conclude that 26 h of mild to moderate resuscitative hypothermia leads not only to brain tissue rescue, but most important to long-lasting behavioral improvement throughout brain maturation despite severity of injury and delayed onset of cooling. (1), a profound, hypoxic-ischemic insult in the human fetus and newborn with a high rate of permanent neuropsychological damage and mortality. A severe acute insult may predominantly affect the thalami, the basal ganglia, the hippocampus, and the brain stem with relative preservation of the cerebral cortex and the subcortical white matter (2). After birth, the clinical signs of perinatal asphyxia include neurologic abnormalities such as coma, seizures, or hypotonia, combined with cardiopulmonary compromise. The newly born infant often requires resuscitation and rapid transfer to the tertiary center for injury severity evaluation and neurologic intensive care. Such support could include specific interventions for hypoxic-ischemic encephalopathy 1 or 2 h into the reperfusion phase from cerebral HI. Despite the fact that perinatal asphyxia closely corresponds to experimental models of cerebral HI, where successful neuroprotective interventions were introduced, presently no agent has been proven useful to ameliorate the chronic handicapping conditions of perinatal asphyxia in the clinical setting (3).In the present clinical situation, neuroprotection can at best be initiated hours after perinatal asphyxia. Such a postischemic or resuscitative neuroprotective measure is hypot...

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Behavioral performance of rats following neonatal hypoxia-ischemia.

Cited by 55 publications

References 16 publications

Long-Term Functional and Protective Actions of Preconditioning With Hypoxia, Cobalt Chloride, and Desferrioxamine Against Hypoxic-Ischemic Injury in Neonatal Rats

Long-Term Functional and Protective Actions of Preconditioning With Hypoxia, Cobalt Chloride, and Desferrioxamine Against Hypoxic-Ischemic Injury in Neonatal Rats

Reoxygenation with 100% Oxygen Versus Room Air: Late Neuroanatomical and Neurofunctional Outcome in Neonatal Mice with Hypoxic-Ischemic Brain Injury

Delayed Postischemic Hypothermia Improves Long-Term Behavioral Outcome after Cerebral Hypoxia-Ischemia in Neonatal Rats

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