Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism
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J. Cereb. Blood Flow Metab. · Aug 2017
Site-specific elevation of interleukin-1β and matrix metalloproteinase-9 in the Willis circle by hemodynamic changes is associated with rupture in a novel rat cerebral aneurysm model.
The pathogenesis of subarachnoid hemorrhage remains unclear. No models of cerebral aneurysms elicited solely by surgical procedures and diet have been established. Elsewhere we reported that only few rats in our original rat aneurysm model manifested rupture at the anterior and posterior Willis circle and that many harbored unruptured aneurysms at the anterior cerebral artery-olfactory artery bifurcation. ⋯ Notably, the level of matrix metalloproteinase-9 associated with interleukin-1β was augmented by the increase in the blood flow volume, suggesting that these molecules exacerbated the vulnerability of the aneurysmal wall. The current study first demonstrates that a site-specific increase in interleukin-1β and matrix metalloproteinase-9 elicited by hemodynamic changes is associated with rupture. Our novel rat model of rupture may help to develop pharmaceutical approaches to prevent rupture.
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J. Cereb. Blood Flow Metab. · Jul 2017
Intranasal administration of vitamin D attenuates blood-brain barrier disruption through endogenous upregulation of osteopontin and activation of CD44/P-gp glycosylation signaling after subarachnoid hemorrhage in rats.
In this study, we investigated the role of vitamin D3 (VitD3) on endogenous osteopontin (OPN), a neuroprotective glycoprotein, after subarachnoid hemorrhage (SAH). The endovascular perforation SAH model in Sprague-Dawley rats was used to study the effect of intranasal VitD3 (30 ng/kg) before (Pre-SAH + VitD3) and after (Post-SAH + VitD3) subarachnoid hemorrhage. Vitamin D3 (30, 60, 120 ng/kg/day) increased more than one fold endogenous OPN expression in astrocytes and endothelial cells of rat brain. ⋯ OPN expression was significantly higher in Pre-SAH + VitD3 rats, specifically A and C, but not B, isomers were upregulated in the astrocytes, leading to CD44 splicing, and P-gp glycosylation in brain endothelial cells. The results show that intranasal vitamin D3 attenuates blood-brain barrier (BBB) disruption through endogenous upregulation of OPN and subsequent CD44 and P-gp glycosylation signals in brain endothelial cells. Furthermore, this study identifies a novel strategy for the cost-effective management of subarachnoid hemorrhage.
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J. Cereb. Blood Flow Metab. · Jul 2017
Colony stimulating factor 1 receptor inhibition eliminates microglia and attenuates brain injury after intracerebral hemorrhage.
Microglia are the first responders to intracerebral hemorrhage, but their precise role in intracerebral hemorrhage remains to be defined. Microglia are the only type of brain cells expressing the colony-stimulating factor 1 receptor, a key regulator for myeloid lineage cells. Here, we determined the effects of a colony-stimulating factor 1 receptor inhibitor (PLX3397) on microglia and the outcome in the context of experimental mouse intracerebral hemorrhage. ⋯ Importantly, colony-stimulating factor 1 receptor inhibition attenuated neurodeficits and brain edema in two experimental models of intracerebral hemorrhage induced by injection of collagenase or autologous blood. The benefit of colony-stimulating factor 1 receptor inhibition was associated with reduced leukocyte infiltration in the brain and improved blood-brain barrier integrity after intracerebral hemorrhage, and each observation was independent of lesion size or hematoma volume. These results demonstrate that suppression of colony-stimulating factor 1 receptor signaling ablates microglia and confers protection after intracerebral hemorrhage.
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J. Cereb. Blood Flow Metab. · Jun 2017
Glymphatic clearance controls state-dependent changes in brain lactate concentration.
Brain lactate concentration is higher during wakefulness than in sleep. However, it is unknown why arousal is linked to an increase in brain lactate and why lactate declines within minutes of sleep. Here, we show that the glymphatic system is responsible for state-dependent changes in brain lactate concentration. ⋯ Concurrently, the same manipulations diminished accumulation of lactate in cervical, but not in inguinal lymph nodes when mice were anesthetized. Thus, our study suggests that brain lactate is an excellent biomarker of the sleep-wake cycle and increases further during sleep deprivation, because brain lactate is inversely correlated with glymphatic-lymphatic clearance. This analysis provides fundamental new insight into brain energy metabolism by demonstrating that glucose that is not fully oxidized can be exported as lactate via glymphatic-lymphatic fluid transport.
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J. Cereb. Blood Flow Metab. · May 2017
Multicenter StudyOxygen availability and spreading depolarizations provide complementary prognostic information in neuromonitoring of aneurysmal subarachnoid hemorrhage patients.
Multimodal neuromonitoring in neurocritical care increasingly includes electrocorticography to measure epileptic events and spreading depolarizations. Spreading depolarization causes spreading depression of activity (=isoelectricity) in electrically active tissue. If the depression is long-lasting, further spreading depolarizations occur in still isoelectric tissue where no activity can be suppressed. ⋯ Multiple regression showed that both peak total depression duration per recording day and mean baseline tissue partial pressure of oxygen were independent predictors of outcome. Moreover, tissue partial pressure of oxygen preceding spreading depolarization was similar and differences in tissue partial pressure of oxygen responses to spreading depolarization were only subtle between isoelectric spreading depolarizations and spreading depressions. This further supports that, similar to clustering of spreading depolarizations, long spreading depolarization-induced periods of isoelectricity are useful to detect energy compromise remotely, which is valuable because the exact location of future developing pathology is unknown at the time when the neurosurgeon implants recording devices.