Regulation of the Cerebral Circulation During Development

Koehler, Raymond C.

doi:10.1002/cphy.c200028

Cited by 6 publications

(9 citation statements)

References 528 publications

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“…Regulation of CBF in the brain is distinct when comparing premature, neonatal, infant, adolescent, and adult brain ( Rhee et al, 2018 ). CBF regulation begins in utero , and its development continues during the neonatal, infant, and childhood periods ( Koehler, 2021 ). In animal models, multiple studies have found evidence of at least partially functional CBFAR in the fetus ( Tweed et al, 1982 ; Papile et al, 1985 ; Tweed et al, 1986 ) and effective CBFAR in the neonate ( Leffler et al, 1986 ; Brady et al, 2007 ).…”

Section: Discussionmentioning

confidence: 99%

Cerebral Blood Flow Autoregulation in Offspring From Experimentally Preeclamptic Rats and the Effect of Age

et al. 2022

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Preeclampsia is a hypertensive disorder of pregnancy that causes significant, long term cardiovascular effects for both the mother and offspring. A previous study demonstrated that middle cerebral arteries in offspring from an experimental rat model of preeclampsia were smaller, stiffer, and did not enlarge over the course of maturation, suggesting potential hemodynamic alterations in these offspring. Here we investigated the effect of experimental preeclampsia on cerebral blood flow autoregulation in juvenile and adult offspring that were born from normal pregnant or experimentally preeclamptic rats. Relative cerebral blood flow was measured using laser Doppler flowmetry, and cerebral blood flow autoregulation curves were constructed by raising blood pressure and controlled hemorrhage to lower blood pressure. Immunohistochemistry was used to assess middle cerebral artery size. Heart rate and blood pressure were measured in awake adult offspring using implanted radiotelemetry. Serum epinephrine was measured using enzyme-linked immunosorbent assay. Offspring from both groups showed maturation of cerebral blood flow autoregulation as offspring aged from juvenile to adulthood as demonstrated by the wider autoregulatory plateau. Experimental preeclampsia did not affect cerebral blood flow autoregulation in juvenile offspring, and it had no effect on cerebral blood flow autoregulation in adult offspring over the lower range of blood pressures. However, experimental preeclampsia caused a right shift in the upper range of blood pressures in adult offspring (compared to normal pregnant). Structurally, middle cerebral arteries from normal pregnant offspring demonstrated growth with aging, while middle cerebral arteries from experimentally preeclamptic offspring did not, and by adulthood normal pregnant offspring had significantly larger middle cerebral arteries. Middle cerebral artery lumen diameters did not significantly change as offspring aged. Serum epinephrine was elevated in juvenile experimentally preeclamptic offspring, and a greater degree of hemorrhage was required to induce hypotension, suggesting increased sympathetic activity. Finally, despite no evidence of increased sympathetic activity, adult experimentally preeclamptic offspring were found to have persistently higher heart rate. These results demonstrate a significant effect of experimental preeclampsia on the upper range of autoregulation and cerebrovascular structure in juvenile and adult offspring that could have an important influence on brain perfusion under conditions of hypo and/or hypertension.

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Section: Discussionmentioning

confidence: 99%

Cerebral Blood Flow Autoregulation in Offspring From Experimentally Preeclamptic Rats and the Effect of Age

et al. 2022

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“…In humans, postnatal increases in cerebral blood flow are matched with postnatal increases in energy metabolism and presumably heat production, and this principle holds in other species during development. 30 Perhaps factors such as the distance between cephalic arteries and veins and their blood flow may become rate-limiting for heat transfer in the 15-kg piglets.…”

Section: Discussionmentioning

confidence: 99%

“…Other developmental factors that could affect the rate of brain cooling are the size of the brain, cerebral blood flow, and cerebral metabolic heat production resulting from developmental changes in energy production. 30 Before application to pediatric CPR, it is important to determine efficacy of transnasal cooling of brain in different age groups in an animal model of comparable mass to neonates, infants and young children who are most vulnerable to cardiac arrest among the pediatric population. 2 We chose piglets as a pediatric animal model because their body mass, brain mass, and cerebral blood flow scales more closely to these parameters in humans during development than rodent models.…”

Section: Introductionmentioning

confidence: 99%

Rapid, selective and homogeneous brain cooling with transnasal flow of ambient air for pediatric resuscitation

Koehler

Reyes

Hopkins

et al. 2023

J Cereb Blood Flow Metab

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Neurologic outcome from out-of-hospital pediatric cardiac arrest remains poor. Although therapeutic hypothermia has been attempted in this patient population, a beneficial effect has yet to be demonstrated, possibly because of the delay in achieving target temperature. To minimize this delay, we developed a simple technique of transnasal cooling. Air at ambient temperature is passed through standard nasal cannula with an open mouth to produce evaporative cooling of the nasal passages. We evaluated efficacy of brain cooling with different airflows in different size piglets. Brain temperature decreased by 3°C within 25 minutes with nasal airflow rates of 16, 32, and 16 L/min in 1.8-, 4-, and 15-kg piglets, respectively, whereas rectal temperature lagged brain temperature. No substantial spatial temperature gradients were seen along the neuroaxis, suggesting that heat transfer is via blood convection. The evaporative cooling did not reduce nasal turbinate blood flow or sagittal sinus oxygenation. The rapid and selective brain cooling indicates a high humidifying capacity of the nasal turbinates is present early in life. Because of its simplicity, portability, and low cost, transnasal cooling potentially could be deployed in the field for early initiation of brain cooling prior to maintenance with standard surface cooling after pediatric cardiac arrest.

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“…In addition, one major consideration is the potential age-dependent effect of what constitutes an optimal or dangerous ICP and CPP [ 8 , 9 ]. The range of normal arterial blood pressure (ABP) or CPP as well as the capacity and plateau level for cerebral pressure autoregulation vary extensively throughout childhood [ 10 ]. Although a “safe” lower CPP threshold may be anticipated on an epidemiological level for certain pediatric age groups in TBI, adequate cerebral blood flow (CBF) cannot be guaranteed [ 9 , 10 ].…”

Section: Introductionmentioning

confidence: 99%

“…The range of normal arterial blood pressure (ABP) or CPP as well as the capacity and plateau level for cerebral pressure autoregulation vary extensively throughout childhood [ 10 ]. Although a “safe” lower CPP threshold may be anticipated on an epidemiological level for certain pediatric age groups in TBI, adequate cerebral blood flow (CBF) cannot be guaranteed [ 9 , 10 ]. What defines a sufficient CBF in pediatric TBI in different age groups is not well-determined, since “normal” CBF is highly varied throughout childhood during the different phases of cerebral development and maturation [ 9 , 10 ].…”

Section: Introductionmentioning

confidence: 99%

ICP, PRx, CPP, and ∆CPPopt in pediatric traumatic brain injury: the combined effect of insult intensity and duration on outcome

et al. 2023

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Purpose The aim was to investigate the combined effect of insult intensity and duration, regarding intracranial pressure (ICP), pressure reactivity index (PRx), cerebral perfusion pressure (CPP), and optimal CPP (CPPopt), on clinical outcome in pediatric traumatic brain injury (TBI). Method This observational study included 61 pediatric patients with severe TBI, treated at the Uppsala University Hospital, between 2007 and 2018, with at least 12 h of ICP data the first 10 days post-injury. ICP, PRx, CPP, and ∆CPPopt (actual CPP-CPPopt) insults were visualized as 2-dimensional plots to illustrate the combined effect of insult intensity and duration on neurological recovery. Results This cohort was mostly adolescent pediatric TBI patients with a median age at 15 (interquartile range 12–16) years. For ICP, brief episodes (minutes) above 25 mmHg and slightly longer episodes (20 min) of ICP 20–25 mmHg correlated with unfavorable outcome. For PRx, brief episodes above 0.25 as well as slightly lower values (around 0) for longer periods of time (30 min) were associated with unfavorable outcome. For CPP, there was a transition from favorable to unfavorable outcome for CPP below 50 mmHg. There was no association between high CPP and outcome. For ∆CPPopt, there was a transition from favorable to unfavorable outcome when ∆CPPopt went below −10 mmHg. No association was found for positive ∆CPPopt values and outcome. Conclusions This visualization method illustrated the combined effect of insult intensity and duration in relation to outcome in severe pediatric TBI, supporting previous notions to avoid high ICP and low CPP for longer episodes of time. In addition, higher PRx for longer episodes of time and CPP below CPPopt more than −10 mmHg were associated with worse outcome, indicating a potential role for autoregulatory-oriented management in pediatric TBI.

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Regulation of the Cerebral Circulation During Development

Cited by 6 publications

References 528 publications

Cerebral Blood Flow Autoregulation in Offspring From Experimentally Preeclamptic Rats and the Effect of Age

Cerebral Blood Flow Autoregulation in Offspring From Experimentally Preeclamptic Rats and the Effect of Age

Rapid, selective and homogeneous brain cooling with transnasal flow of ambient air for pediatric resuscitation

ICP, PRx, CPP, and ∆CPPopt in pediatric traumatic brain injury: the combined effect of insult intensity and duration on outcome

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