Monitoring of cerebral blood flow during hypoxia-ischemia and resuscitation in the neonatal rat using laser speckle imaging.

Thomas Wood,Maja Elstad,Elisa Smit,Mari Falck,Marianne Thoresen,Damjan Osredkar,Elke Maes

doi:10.14814/phy2.12749

Thomas Wood, Maja Elstad + Show 5 more

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https://doi.org/10.14814/phy2.12749

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Abstract

Neonatal hypoxic‐ischemic encephalopathy (HIE) is associated with alterations in cerebral blood flow (CBF) as a result of perinatal asphyxia. The extent to which CBF changes contribute to injury, and whether treatments that ameliorate these changes might be neuroprotective, is still unknown. Higher throughput techniques to monitor CBF changes in rodent models of HIE can help elucidate the underlying pathophysiology. We developed a laser speckle imaging (LSI) technique to continuously monitor CBF in 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, CBF to the ligated side fell by 30% compared to the unligated side (P < 0.0001). Hypoxia induced a bilateral 55% reduction in CBF, which was partially restored by resuscitation. Compared to resuscitation in air, resuscitation in 100% oxygen increased CBF to the ligated side by 45% (P = 0.033). Individual variability in CBF response 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 unilateral HI, resuscitation in 100% oxygen did not affect hemispheric area loss, or hippocampal CA1 pyramidal neuron counts, after 1‐week survival. Continuous CBF monitoring using LSI in multiple rodents simultaneously can screen potential treatment modalities that affect CBF, and provide insight into the pathophysiology of HI.

Highlights

Perinatal asphyxia is a major cause of morbidity and mortality, with 1–2 per 1000 infants born at term experiencing perinatal asphyxia that results in hypoxic-ischemic encephalopathy (HIE) (Kurinczuk et al 2010)
On the ligated side during the resuscitation period, median flux in the group resuscitated in 100% oxygen (396 au, range 260–592 au) was 45% greater than in the group resuscitated in 21% oxygen (274 au, 228– 540 au)
A trend (P = 0.093) toward increased flux in the group resuscitated in 100% oxygen remained

Summary

Introduction

Perinatal asphyxia is a major cause of morbidity and mortality, with 1–2 per 1000 infants born at term experiencing perinatal asphyxia that results in hypoxic-ischemic encephalopathy (HIE) (Kurinczuk et al 2010). The hypoxicischemic (HI) insult results in a primary energy failure, characterized by an inability to regenerate high-energy phosphates, and loss of regulated ATP-dependent processes in the brain, such as maintenance of ion homeostasis (Hansen 1985; Thoresen et al 1995; Wassink et al 2014) Though current treatments, such as TH, focus on the secondary effects of HI-induced brain injury in asphyxiated neonates, there is ongoing interest in studying cerebral blood flow (CBF) changes during HI and resuscitation, as knowledge regarding the restoration of CBF following neonatal HI is still limited. In order to test the feasibility of using this method to explore methods of resuscitation and their effect on CBF, a comparison of CBF changes in rats resuscitated in 21% or 100% oxygen, and how those changes correlate with neuropathology, was investigated

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