Selective reduction of blood flow to white matter during hypotension in newborn dogs: A possbile mechanism of periventricular leukomalacia

Richard, Serge; Hernández, M. J.; Yagel, Susan K.

doi:10.1002/ana.410120506

Cited by 142 publications

(10 citation statements)

References 12 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This is in agreement with a previous study, which showed that blood flow to many areas of white matter was impaired during severe systemic hypotension in young dogs, but blood flow to all gray matter areas was preserved. 8 A similar observation was also made in ischemic leukoaraiosis. 7…”

Section: Discussionsupporting

confidence: 64%

Two-photon microscopic imaging of capillary red blood cell flux in mouse brain reveals vulnerability of cerebral white matter to hypoperfusion

Ohtomo

Thunemann

et al. 2019

J Cereb Blood Flow Metab

View full text Add to dashboard Cite

Despite the importance of understanding the regulation of microvascular blood flow in white matter, no data on subcortical capillary blood flow parameters are available, largely due to the lack of appropriate imaging methods. To address this knowledge gap, we employed two-photon microscopy using a far-red fluorophore Alexa680 and photon-counting detection to measure capillary red blood cell (RBC) flux in both cerebral gray and white matter, in isoflurane-anesthetized mice. We have found that in control animals, baseline capillary RBC flux in the white matter was significantly higher than in the adjacent cerebral gray matter. In response to mild hypercapnia, RBC flux in the white matter exhibited significantly smaller fractional increase than in the gray matter. Finally, during global cerebral hypoperfusion, RBC flux in the white matter was reduced significantly in comparison to the controls, while RBC flux in the gray matter was preserved. Our results suggest that blood flow in the white matter may be less efficiently regulated when challenged by physiological perturbations as compared to the gray matter. Importantly, the blood flow in the white matter may be more susceptible to hypoperfusion than in the gray matter, potentially exacerbating the white matter deterioration in brain conditions involving global cerebral hypoperfusion.

show abstract

Section: Discussionsupporting

confidence: 64%

Two-photon microscopic imaging of capillary red blood cell flux in mouse brain reveals vulnerability of cerebral white matter to hypoperfusion

Ohtomo

Thunemann

et al. 2019

J Cereb Blood Flow Metab

View full text Add to dashboard Cite

show abstract

“…Several models of inflammatory postnatal brain injury have been developed in different species, including mouse ( 52 – 56 ), rat ( 57 – 59 ), rabbit ( 60 , 61 ), dog ( 62 ), and others ( 63 ). Rodent models are most widely used due to ease of use and relatively short reproductive cycle.…”

Section: Il-1ra and Pathogenic Models Of Postnatal Brain Injurymentioning

confidence: 99%

Interleukin-1 Receptor Blockade in Perinatal Brain Injury

2014

View full text Add to dashboard Cite

Interleukin-1 (IL-1) is a potent inflammatory cytokine that can be produced by a variety of cell types throughout the body. While IL-1 is a central mediator of inflammation and response to infection, the role of IL-1 signaling in adult and pediatric brain injury is becoming increasingly clear. Although the mechanisms of IL-1 expression are largely understood, the downstream effects and contributions to excitotoxicity and oxidative stress are poorly defined. Here, we present a review of mechanisms of IL-1 signaling with a focus on the role of IL-1 in perinatal brain injury. We highlight research models of perinatal brain injury and the use of interleukin-1 receptor antagonist (IL-1RA) as an agent of therapeutic potential in preventing perinatal brain injury due to exposure to inflammation.

show abstract

“…TLR-4 receptors were found in the immature brain, and LPS administration induced an increased expression of CD14 [69]. In addition to the inflammatory response [91,92], LPS induces hypoperfusion [93], hypoglycemia [93], hyperthermia [91] and lactic acidosis, which may important factors triggering brain damage. In fact, a high dose of LPS (12 mg/kg) induced hypotension (50% decrease) as well as decrease in cerebral blood flow (CBF) in white matter, suggesting that hypoperfusion is an important contributor to injury in this region [93].…”

Section: Animal Models Of Pvlmentioning

confidence: 99%

Animal Models of Periventricular Leukomalacia

et al. 2011

View full text Add to dashboard Cite

Periventricular leukomalacia, specifically characterized as white matter injury, in neonates is strongly associated with the damage of pre-myelinating oligodendrocytes. Clinical data suggest that hypoxia-ischemia during delivery and intrauterine or neonatal infection-inflammation are important factors in the etiology of periventricular leukomalacia including cerebral palsy, a serious case exhibiting neurobehavioral deficits of periventricular leukomalacia. In order to explore the pathophysiological mechanisms of white matter injury and to better understand how infectious agents may affect the vulnerability of the immature brain to injury, novel animal models have been developed using hypoperfusion, microbes or bacterial products (lipopolysaccharide) and excitotoxins. Such efforts have developed rat models that produce predominantly white matter lesions by adopting combined hypoxia-ischemia technique on postnatal days 1-7, in which unilateral or bilateral carotid arteries of animals are occluded (ischemia) followed by 1-2 hour exposure to 6-8% oxygen environment (hypoxia). Furthermore, low doses of lipopolysaccharide that by themselves have no adverse-effects in 7-day-old rats, dramatically increase brain injury to hypoxic-ischemic challenge, implying that inflammation sensitizes the immature central nervous system. Therefore, among numerous models of periventricular leukomalacia, combination of hypoxia-ischemia-lipopolysaccharide might be one of the most-acceptable rodent models to induce extensive white matter injury and ensuing neurobehavioral deficits for the evaluation of candidate therapeutics.

show abstract

Selective reduction of blood flow to white matter during hypotension in newborn dogs: A possbile mechanism of periventricular leukomalacia

Cited by 142 publications

References 12 publications

Two-photon microscopic imaging of capillary red blood cell flux in mouse brain reveals vulnerability of cerebral white matter to hypoperfusion

Two-photon microscopic imaging of capillary red blood cell flux in mouse brain reveals vulnerability of cerebral white matter to hypoperfusion

Interleukin-1 Receptor Blockade in Perinatal Brain Injury

Animal Models of Periventricular Leukomalacia

Contact Info

Product

Resources

About