Early cell death in the brain of fetal preterm lambs after hypoxic–ischemic injury

Goñi‐de‐Cerio, Felipe; Álvarez, Antonia; Caballero, A; Mielgo, Victoria; Álvarez, Francisco J.; Rey-Santano, M C; Gastiasoro, Elena; Valls‐i‐Soler, Adolf; Bilbao, Juan; Hilario, Enrique

doi:10.1016/j.brainres.2007.03.013

Cited by 26 publications

(43 citation statements)

References 49 publications

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“…Leakage is accompanied by a decrease in the percentage of cells which are S-100 immunoreactive ( fig. 3 ), which is not accompanied by an increase in its expression [55] , suggesting a depletion of S-100 in brain cells.…”

Section: Astrocytesmentioning

confidence: 93%

Hypoxic-Ischemic Injury in the Immature Brain – Key Vascular and Cellular Players

et al. 2007

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Over the past decade, much has been learned about the cellular and molecular mechanisms underlying hypoxic-ischemic (H-I) injury in the preterm human brain. The pathogenesis of H-I brain injury is now understood to be multifactorial and quite complex, depending on (i) the severity, intensity and timing of asphyxia, (ii) selective ischemic vulnerability, (iii) the degree of maturity of the brain, and (iv) the characteristics of the ensuing reoxygenation/reperfusion phase. Each of these factors has differential effects on the distinct cell populations in the brain, with certain specific cell types being particularly vulnerable in the developing brain. In this review, we discuss the role of the blood vessels and the distinct cell populations, which are the mayor constitutive elements of the immature brain, in the pathophysiology of H-I lesion. The presence of fragile and poorly anastomosed blood vessels and the existence of disturbances in the blood-brain barrier alter blood flow, vascular tone and nutrient delivery. Brain cells are sensitive to the overstimulation of neurotransmitter receptors, particularly glutamate receptors, which can provoke excitotoxicity leading to the death of neurons and other cells such as astrocytes and oligodendrocyte progenitors. Microglial activation by means of excitatory amino acids and by leukocyte migration initiates the inflammatory response giving rise to an increase in regional cerebral blood flow and promoting astrocyte and oligodendrocyte injuries. A better understanding of these aspects of H-I injury will contribute to more efficient strategies for the management of the associated damage.

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Section: Astrocytesmentioning

confidence: 93%

Hypoxic-Ischemic Injury in the Immature Brain – Key Vascular and Cellular Players

et al. 2007

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“…Involuting mammary gland sections were used as positive controls for the TUNEL method (not shown). Apoptotic cells were detected [11,33] as fragmented deoxyribonucleic acid combined with the use of morphological criteria (regularly shaped, round condensed or fragmented chromatin, cytoplasmic shrinkage and apoptotic bodies). When evaluating TUNEL positivity, a few cells containing diffusely stained or irregularly fragmented chromatin or breakdown of nuclear and plasma membranes or swollen cytoplasms were observed.…”

Section: Tunel Methodsmentioning

confidence: 99%

“…The experimental protocol met the European Union regulations for animal research (EU 86/609) and has been described elsewhere [11,[32][33][34]. Our model of intrauterine asphyxia of the fetus by means of partial cord occlusion [32] pretends to be similar to the situation of the neonatal or pediatric critical care unit.…”

Section: Surgical Proceduresmentioning

confidence: 99%

“…Using a lamb model of perinatal asphyxia, we have previously reported that the reduction of the umbilical blood flow leads to brain damage [11,32] and that the administration of the cannabinoid agonist WIN 55,212-2 decreases brain injury reducing both delayed cell death and glial damage [33].…”

Section: Introductionmentioning

confidence: 99%

“…Anaerobic metabolism leads to a rapid depletion of adenosine triphosphate (ATP), accumulation of lactic acid and failure of ion pumps, resulting in a massive entry of sodium, calcium, and water into the cells. Afterwards, multiple and diverse downstream biochemical reactions aggravate the pathogenesis of hypoxicischemic brain damage, being the most important, among others, the massive increase in free cytosolic calcium concentrations, the production of reactive oxygen species leading to oxidative stress by lipid peroxidation, and the drop in mitochondrial function triggering the activation of apoptotic pathways, DNA fragmentation and cell death [6][7][8][9][10][11]. Such a complexity of neonatal hypoxic-ischemic pathophysiology determines that successful neuroprotection could be achieved only by multi-therapeutic approaches [3] and optimizing therapy for neonatal brain injury will require capitalizing on multiple pathways which prevent cell death [12].…”

Section: Introductionmentioning

confidence: 99%

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The Cannabinoid WIN 55212-2 Mitigates Apoptosis and Mitochondrial Dysfunction After Hypoxia Ischemia

Alonso-Alconada

Álvarez

et al. 2011

Neurochem Res

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Perinatal hypoxia-ischemia has significant mortality and morbidity due to there is still no specific treatment as a consequence of the complexities of hypoxic-ischemic pathophysiology. The aim of this work was to evaluate the effects of the cannabinoid agonist WIN 55212-2 on apoptotic cell death and mitochondrial dysfunction after perinatal asphyxia in fetal lambs. Animals were assigned to: one SHAM group and two hypoxic-ischemic groups that received a dose of 0.01 μg/kg WIN 55,212-2 (HI + WIN) or not (HI + VEH) after 60 min of partial occlusion of the umbilical cord, and sacrificed 3 h later. Different brain regions were separated for morphological studies, and the same territories were dissociated and analyzed by flow cytometry to quantify apoptosis, to determine mitochondrial integrity and transmembrane potential and to analyze intracellular calcium levels. Our results showed that WIN 55,212-2 reduced apoptotic cell death in all regions studied through the maintenance of mitochondrial integrity and functionality.

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Cell Death

2009

Ultrastructural Pathology the Comparative Cellular Basis of Disease

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Early cell death in the brain of fetal preterm lambs after hypoxic–ischemic injury

Cited by 26 publications

References 49 publications

Hypoxic-Ischemic Injury in the Immature Brain – Key Vascular and Cellular Players

Hypoxic-Ischemic Injury in the Immature Brain – Key Vascular and Cellular Players

The Cannabinoid WIN 55212-2 Mitigates Apoptosis and Mitochondrial Dysfunction After Hypoxia Ischemia

Cell Death

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