BackgroundPrevailingly, adult mammalian neurogenesis is thought to occur in discrete, separate locations known as neurogenic niches that are best characterized in the subgranular zone (SGZ) of the dentate gyrus and in the subventricular zone (SVZ). The existence of adult human neurogenic niches is controversial.MethodsThe existence of neurogenic niches was investigated with neurogenesis marker immunostaining in histologically normal human brains obtained from autopsies. Twenty-eight adult temporal lobes, specimens from limbic structures and the hypothalamus of one newborn and one adult were examined.ResultsThe neural stem cell marker nestin stained circumventricular organ cells and the immature neuronal marker doublecortin (DCX) stained hypothalamic and limbic structures adjacent to circumventricular organs; both markers stained a continuous structure running from the hypothalamus to the hippocampus. The cell proliferation marker Ki-67 was detected predominately in structures that form the septo-hypothalamic continuum. Nestin-expressing cells were located in the fimbria-fornix at the insertion of the choroid plexus; ependymal cells in this structure expressed the putative neural stem cell marker CD133. From the choroidal fissure in the temporal lobe, a nestin-positive cell layer spread throughout the SVZ and subpial zone. In the subpial zone, a branch of this layer reached the hippocampal sulcus and ended in the SGZ (principally in the newborn) and in the subiculum (principally in the adults). Another branch of the nestin-positive cell layer in the subpial zone returned to the optic chiasm. DCX staining was detected in the periventricular and middle hypothalamus and more densely from the mammillary body to the subiculum through the fimbria-fornix, thus running through the principal neuronal pathway from the hippocampus to the hypothalamus. The column of the fornix forms part of this pathway and appears to coincide with the zone previously identified as the human rostral migratory stream. Partial co-labeling with DCX and the neuronal marker βIII-tubulin was also observed.ConclusionsCollectively, these findings suggest the existence of an adult human neurogenic system that rises from the circumventricular organs and follows, at minimum, the circuitry of the hypothalamus and limbic system.

BackgroundTo assess whether circadian patterns of temperature correlate with further values of intracranial pressure (ICP) in severe brain injury treated with hypothermia.MethodsWe retrospectively analyzed temperature values in subarachnoid hemorrhage patients treated with hypothermia by endovascular cooling. The circadian patterns of temperature were correlated with the mean ICP across the following day (ICP24).ResultsWe analyzed data from 17 days of monitoring of three subarachnoid hemorrhage patients that underwent aneurysm coiling, sedation and hypothermia due to refractory intracranial hypertension and/or cerebral vasospasm. ICP24 ranged from 11.5 ± 3.1 to 24.2 ± 6.2 mmHg. The ratio between the coefficient of variation of temperature during the nocturnal period (18:00–6:00) and the preceding diurnal period (6:00–18:00) [temperature variability (TV)] ranged from 0.274 to 1.97. Regression analysis showed that TV correlated with ICP24 (Pearson correlation = −0.861, adjusted R square = 0.725, p < 0.001), and that ICP24 = 6 (4–TV) mmHg or, for 80% prediction interval,  mmHg. The results indicate that the occurrence of ICP24 higher than 20 mmHg is unlikely after a day with TV ≥1.0.ConclusionsTV correlates with further ICP during hypothermia regardless the strict range that temperature is maintained. Further studies with larger series could clarify whether intracranial hypertension in severe brain injury can be predicted by analysis of oscillation patterns of autonomic parameters across a period of 24 h or its harmonics.Electronic supplementary materialThe online version of this article (doi:10.1186/s12967-017-1272-y) contains supplementary material, which is available to authorized users.

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BACKGROUND:Stroke, including subarachnoid hemorrhage (SAH), is one of the leading causes of morbidity and mortality worldwide. The mortality rate of poor-grade SAH ranges from 34% to 52%. In an attempt to improve SAH outcomes, clinical research on multimodality monitoring has been performed, as has basic science research on inflammation and neuroregeneration (which can occur due to injury-induced neurogenesis). Nevertheless, the current literature does not focus on the integrated study of these fields. Multimodality monitoring corresponds to physiological data obtained during clinical management by both noninvasive and invasive methods. Regarding inflammation and neuroregeneration, evidence suggests that, in all types of stroke, a proinflammatory phase and an anti-inflammatory phase occur consecutively; these phases affect neurogenesis, which is also influenced by other pathophysiological features of stroke, such as ischemia, seizures, and spreading depression.OBJECTIVE:To assess whether injury-induced neurogenesis is a prognostic factor in poor-grade SAH that can be monitored and modulated.METHODS:We propose a protocol for multimodality monitoring-guided hypothermia in poor-grade SAH in which cellular and molecular markers of inflammation and neuroregeneration can be monitored in parallel with clinical and multimodal data.EXPECTED OUTCOMES:This study may reveal correlations between markers of inflammation and neurogenesis in blood and cerebrospinal fluid, based on clinical and multimodality monitoring parameters.DISCUSSION:This protocol has the potential to lead to new therapies for acute, diffuse, and severe brain diseases.ABBREVIATIONS:BBB, blood-brain barrierCPP, cerebral perfusion pressureEEG, electroencephalographyICP, intracranial pressureIL, interleukinMCA, middle cerebral arterySAH, subarachnoid hemorrhageSD, spreading depressionSGZ, subgranular zoneSVZ, subventricular zoneTCD, transcranial Doppler

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We have recently found that the temperature variability (TV) in the day–night cycle may predict the mean intracranial pressure in the following 24 h (ICP24) in subarachnoid hemorrhage (SAH) patients under multimodality monitoring, sedation, and hypothermia (<35°C). Specifically, we found that ICP24 = 6 (4 − TV) mmHg. TV is the ratio between the coefficient of variation of temperature during the nocturnal and the preceding diurnal periods. This result suggests that the circadian clock reflects brain plasticity mechanisms and its malfunctioning leads to deterioration of the neurologic status. The sleep–wake cycle is absent in these patients and their circadian clock can function properly only by environment light-independent mechanisms. One mechanism involves the circadian clock proteins named cryptochromes (CRYs). CRYs are highly preserved and widespread in the evolutionary tree, are expressed in different cell types in humans [type II CRYs, in two forms: human cryptochrome 1 and 2 (hCRY1 and hCRY2)], and in certain species, respond to blue light and play role in magnetoreception. Interestingly, SAH outcome seems to correlate with inflammation, and CRYs decrease inflammatory activity. Our hypothesis derived from these observations is that CRYs modulate the circadian oscillation of temperature even during therapeutic hypothermia and improve outcome in SAH through decrease in inflammation. A strategy to test this hypothesis is to measure periodically during the acute phase of high-grade SAH the level of CRYs in cerebrospinal fluid (CSF) and circulating white blood cells, and to correlate these levels with outcome, TV, ICP24, and pro- and anti-inflammatory markers in CSF and blood. If this hypothesis is true, the development of therapies targeting inflammation in SAH could take advantage of cryptochrome properties. It has been shown that blue light phototherapy increases the expression of CRYs in blood mononuclear cells in jaundiced neonates. Likewise, visual stimulus with flashing light improves Alzheimer’s disease features in experimental model and there is a prominent expression of CRYs in the retina. Remarkably, recent evidence showed that hCRY2 responds to electromagnetic fields, which could be one elusive mechanism of action of transcranial magnetic stimulation and a reason for its use in SAH.

CONTEXT: Transperitoneal migration is a mechanism for oocyte retrieval that is generally demonstrated in certain cases of ectopic pregnancy. However, the association between these two conditions is debatable. The rare occasions on which intrauterine pregnancy following transperitoneal migration can be documented are an opportunity for studying this topic. CASE REPORT: We report the case of a female with a history of salpingectomy due to an ectopic pregnancy at 31 years of age. Two subsequent pregnancies were intrauterine. In both of them, ultrasound revealed that the corpus luteum was located in the ovary ipsilateral to the salpingectomy. CONCLUSION: To our knowledge, this is the first reported case of two intrauterine pregnancies following transperitoneal migration, carried to term, and resulting in the delivery of two healthy children. The clinical and physiological implications are discussed.resUMo CONTEXTO: A migração transperitoneal é um mecanismo de captação do oócito demonstrado, em geral, em determinados casos de gravidez ectópica. No entanto, a associação entre ambas é discutível. As raras ocasiões em que uma gestação intrauterina após migração transperitoneal pode ser documentada são uma oportunidade para o estudo deste tópico. RELATO DE CASO: Relatamos o caso de uma mulher com salpingectomia aos 31 anos, por gravidez ectó-pica. Duas gestações subsequentes foram intrauterinas. Em ambas, ultrassonografia evidenciou presença do corpo lúteo em ovário do mesmo lado da salpingectomia. CONCLUSÃO: No nosso conhecimento, trata-se do primeiro caso relatado com duas gestações intrauterinas após migração transperitoneal, terminadas com o nascimento de duas crianças saudáveis. As implicações clínicas e fisiológicas são discutidas.

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