Newborn piglets exposed to acute hypoxia-ischemia (HI) received i.v. cannabidiol (HI ϩ CBD) or vehicle (HI ϩ VEH). In HI ϩ VEH, 72 h post-HI brain activity as assessed by amplitudeintegrated EEG (aEEG) had only recovered to 42 Ϯ 9% of baseline, near-infrared spectroscopy (NIRS) parameters remained lower than normal, and neurobehavioral performance was abnormal (27.8 Ϯ 2.3 points, normal 36). In the brain, there were fewer normal and more pyknotic neurons, while astrocytes were less numerous and swollen. Cerebrospinal fluid concentration of neuronal-specific enolase (NSE) and S100␤ protein and brain tissue percentage of TNF␣(ϩ) cells were all higher. In contrast, in HI ϩ CBD, aEEG had recovered to 86 Ϯ 5%, NIRS parameters increased, and the neurobehavioral score normalized (34.3 Ϯ 1.4 points). HI induced histological changes, and NSE and S100␤ concentration and TNF␣(ϩ) cell increases were suppressed by CBD. In conclusion, post-HI administration of CBD protects neurons and astrocytes, leading to histological, functional, biochemical, and neurobehavioral improvements.

Despite advances in neonatal care, hypoxic-ischemic brain injury is still a serious clinical problem, which is responsible for many cases of perinatal mortality, cerebral palsy, motor impairment and cognitive deficits. Resveratrol, a natural polyphenol with important anti-oxidant and anti-inflammatory properties, is present in grapevines, peanuts and pomegranates. The aim of the present work was to evaluate the possible neuroprotective effect of resveratrol when administered before or immediately after a hypoxic-ischemic brain event in neonatal rats by analyzing brain damage, the mitochondrial status and long-term cognitive impairment. Our results indicate that pretreatment with resveratrol protects against brain damage, reducing infarct volume, preserving myelination and minimizing the astroglial reactive response. Moreover its neuroprotective effect was found to be long lasting, as behavioral outcomes were significantly improved at adulthood. We speculate that one of the mechanisms for this neuroprotection may be related to the maintenance of the mitochondrial inner membrane integrity and potential, and to the reduction of reactive oxygen species. Curiously, none of these protective features was observed when resveratrol was administered immediately after hypoxia-ischemia.

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.

One of the most common causes of mortality and morbidity in children is perinatal hypoxia-ischemia (HI). In spite of the advances in neonatology, its incidence is not diminishing, generating a pediatric population that will require an extended amount of chronic care throughout their lifetime. For this reason, new and more effective neuroprotective strategies are urgently required, in order to minimize as much as possible the neurological consequences of this encephalopathy. In this sense, interest has grown in the neuroprotective possibilities of melatonin, as this hormone may help to maintain cell survival through the modulation of a wide range of physiological functions. Although some of the mechanisms by which melatonin is neuroprotective after neonatal asphyxia remain a subject of investigation, this review tries to summarize some of the most recent advances related with its use as a therapeutic drug against perinatal hypoxic-ischemic brain injury, supporting the high interest in this indoleamine as a future feasible strategy for cerebral asphyctic events.

Hypoxic–ischemic brain damage is an alarming health and economic problem in spite of the advances in neonatal care. It can cause mortality or detrimental neurological disorders such as cerebral palsy, motor impairment and cognitive deficits in neonates. When hypoxia–ischemia occurs, a multi-faceted cascade of events starts out, which can eventually cause cell death. Lower levels of oxygen due to reduced blood supply increase the production of reactive oxygen species, which leads to oxidative stress, a higher concentration of free cytosolic calcium and impaired mitochondrial function, triggering the activation of apoptotic pathways, DNA fragmentation and cell death. The high incidence of this type of lesion in newborns can be partly attributed to the fact that the developing brain is particularly vulnerable to oxidative stress. Since antioxidants can safely interact with free radicals and terminate that chain reaction before vital molecules are damaged, exogenous antioxidant therapy may have the potential to diminish cellular damage caused by hypoxia–ischemia. In this review, we focus on the neuroprotective effects of antioxidant treatments against perinatal hypoxic–ischemic brain injury, in the light of the most recent advances.

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Isomere Fullerentrimere wurden mechanochemisch hergestellt und Langmuir‐Filme von ihnen auf Au(111)‐Oberflächen durch Rastertunnelmikroskopie (RTM) untersucht. Jedes der Isomere zeichnet sich durch eine andere Oberflächenmorphologie aus. Die beobachtete Verteilung der Isomere ist im Einklang mit MO‐Rechnungen zu ihrer Stabilität. Durch RTM können die einzelnen Isomere unterschieden werden (Beispiel siehe Bild), was mit spektroskopischen Methoden schwierig ist.

We have studied the expression of FGF1 and FGF2 during mouse odontogenesis by immunohistochemistry. FGF1 was detected in differentiated odontoblasts and at the secretory pole of ameloblasts. Localization of FGF2 was mainly observed within the basement membrane interposed between dental epithelium and dental mesenchyme. These findings indicate that FGF1 and FGF2 may participate in the control of odontoblast and ameloblast differentiation. Thereafter, we studied the ability of FGF1 and FGF2, alone or in combination with TGF beta 1, to induce polarization and/or functional differentiation of preodontoblasts. Dental papillae (DP) obtained from first lower molars of 17-day-old mouse embryo were cultured in the presence or the absence of growth factors. DP cultured with FGF1 + TGF beta 1 showed gradients of odontoblast-like cell differentiation, which displayed alkaline phosphatase reactivity. DP treated with FGF2 + TGF beta 1 exhibited pre-odontoblast cell polarization, and the cell bodies displayed long cytoplasm processes. However, following this treatment we did not observe extracellular matrix secretion, and alkaline phosphatase activity was completely inhibited. In summary, our results show that exogenous addition of FGF1 to pre-odontoblasts induces their terminal differentiation, by synergistically acting with TGF beta 1. In contrast, FGF2 may regulate the effect of TGF beta 1, permitting cell polarization but restraining pre-odontoblast functions.