Results of Therapy Using Oral Anticoagulants in the Acute Phase after Mechanical Thrombectomy.

Objective: The usage of oral anticoagulants (OACs) in the acute phase of cerebral infarction has increased, but the optimal timing for starting OACs after mechanical thrombectomy (MT) is unclear. We report the usage of OACs after MT at our hospital and evaluated the outcomes. Methods: OACs were selected as secondary preventive drugs for 64 patients who underwent MT for anterior circulatory embolism between July 2016 and January 2019. Of the 64 patients, 28 and 36 received direct oral anticoagulants (DOACs) and warfarin (Wf), respectively. We compared the frequency of intracranial hemorrhage in the acute phase and that of recurrent cerebral infarction within 30 days. Results: The median diffusion-weighted imaging-Alberta Stroke Program Early Computed Tomography Scores + white matter (DWI-ASPECTS + W) score at admission was 7.5 (IQR 6-9)/8 (IQR, 6-9) in the DOACs group/Wf group. The rate of recanalization with modified thrombolysis in cerebral infarction (TICI) ≥2B by MT was 89.3/80.6%. In patients with subarachnoid hemorrhage (SAH) associated with MT and patients with hemorrhagic transformation (HT) on MRI the next day, administration was started after hemostasis. The median timing of the first anticoagulant administration was 3 (IQR, 2-4)/2 (IQR, 1-4) days. In the case of no HT the next day, the rate of new HT after 1 week was 7.1%/29.1%. In the case of HT the next day, the rate of HT deterioration the next day was 7.1%/16.6%. The percentage of symptomatic bleeding was 0%/2.8%. The percentage of recurrent cerebral infarction within 30 days was 0%/2.8%. Conclusion: OACs in the acute phase after MT can be safely used and are expected to be effective at preventing recurrence.

[Preventing Crying after Revascularization Surgery in Pediatric Patients with Moyamoya Disease:Sedation with Dexmedetomidine].

BACKGROUND: Hyperventilation is a well-known risk factor of ischemic events in pediatric patients with moyamoya disease. For young children, it is important to avoid crying to prevent ischemic events because of their unstable postoperative hemodynamics. To prevent crying in pediatric patients, we used dexmedetomidine(DEX)for sedation immediately after revascularization surgery. OBJECTIVE: We investigated the effects of postoperative DEX use on hemodynamic changes and the avoidance of crying and hypocapnia in pediatric patients with moyamoya disease. CASE: Ten consecutive patients(5 boys and 5 girls)who underwent surgical revascularization were enrolled, and 16 hemispheres(8 boys and 8 girls)were sedated with DEX postoperatively between August 2011 and August 2016. METHODS: During extubation after revascularization, DEX was started at 0.4µg/kg/hr under spontaneous breathing and its dose was increased depending on the degree of consciousness, to maintain sedation of at least 3 on the Ramsay scale. DEX administration was terminated the next morning. RESULTS: Sedation was maintained well in all patients without hypocapnia, and no ischemic complications were observed. One patient cried and needed additional intravenous DEX injections and was immediately re-sedated;no hypocapnia developed. Respiratory depression did not occur and changes in respiratory rate and decreases in SpO2 were not observed. No significant changes in systolic blood pressure and heart rate were observed. CONCLUSION: Dexmedetomidine is safe and useful for postoperative sedation in children with moyamoya disease.

Identification of autotaxin as a neurite retraction-inducing factor of PC12 cells in cerebrospinal fluid and its possible sources.

Abstract Cerebrospinal fluid (CSF) induced neurite retraction of differentiated PC12 cells; the action was observed in 15 min (a rapid response) and the activity further increased until 6 h (a long-acting response) during exposure of CSF to the cells. The CSF action was sensitive to monoglyceride lipase and diminished by homologous desensitization with lysophosphatidic acid (LPA) and by pretreatment with an LPA receptor antagonist Ki16425. Although fresh CSF contains LPA to some extent, the LPA content in the medium was increased during culture of PC12 cells with CSF. The rapid response was mimicked by exogenous LPA, and a long-acting response was duplicated by a recombinant autotaxin, lysophospholipase D (lyso-PLD). Although the lyso-PLD substrate lysophosphatidylcholine (LPC) was not detected in CSF, lyso-PLD activity and an approximately 120-kDa autotaxin protein were detected in CSF. On the other hand, LPC but not lyso-PLD activity was detected in the conditioned medium of a PC12 cell culture without CSF. Among neural cells examined, leptomeningeal cells expressed the highest lyso-PLD activity and autotaxin protein. These results suggest that leptomeningeal cells may work as one of the sources for autotaxin, which may play a critical role in LPA production and thereby regulate axonal and neurite morphological change.

Effects of interleukin-1beta and prostaglandin E2 on prostaglandin D synthase production in cultivated rat leptomeningeal cells.

Although the interleukin (IL)-1 receptor is densely distributed in the leptomeninges constituting the blood/cerebrospinal fluid barrier, its physiologic significance has remained unclear. In the present study, we show that in cultured leptomeningeal cells, IL-1beta, tumor necrosis factors, or lipopolysaccharide causes a prominent increase in the synthesis and release of prostaglandin (PG) D synthase, which catalyzes the final step in the biosynthesis of PGD2. Although significant increases in the amount of PGD synthase were also observed with cells exposed to somatostatin, thrombin, or ciliary neurotrophic factor, these were much smaller than were those induced by the proinflammatory cytokines. Other agents tested including IGF-I had no effect upon the enzyme levels in the culture media. Furthermore, we found that the increased secretion of PGD synthase by IL-1beta was completely inhibited by 10(-7) M PGE2. The same dose of PGD2 or 15-deoxy-Delta(12-14)PGJ2 had no effect upon the IL-1beta action. In addition, PGE2 increased the level of fibronectin and eliminated the expression of zonula occludentes-1, a tight junction-associated protein from cultured cells, effects likely reflecting a loss of barrier integrity. These results demonstrate the importance of inflammatory stimuli as a physiologic regulator of the leptomeningeal cell function.

Chain-length dependence of alpha-helix to beta-sheet transition in polylysine: model of protein aggregation studied by temperature-tuned FTIR spectroscopy.

The chain-length dependence of the alpha-helix to beta-sheet transition in poly(L-lysine) is studied by temperature-tuned FTIR spectroscopy. This study shows that heterogeneous samples of poly(L-lysine), comprising polypeptide chains with various lengths, undergo the alpha-beta transition at an intermediate temperature compared to homogeneous ingredients. This holds true as long as each individual fraction of the polypeptide is capable of adopting an antiparallel beta-sheet structure. The tendency is that the longer chain is, the lower the alpha-beta transition temperature is, which has been linked to the presence of distorted or solvated helices with turns or beta sheets in elongating chains of poly(L-lysine). As such helical structures are apparently conducive to the alpha-beta transition, this draws a comparison to the hypothesis of metastable protein conformational states being a common stage in amyloid-formation pathways. The antiparallel architecture of the beta sheet is likely to reflect the pretransition interhelical interactions in poly(L-lysine). Namely, the chains are arranged in an antiparallel manner because of energetically favored antiparallel pre-assembly of dipolar alpha helices.

Assessment of the role of sphingosine 1-phosphate and its receptors in high-density lipoprotein-induced stimulation of astroglial cell function.

It has been suggested that lipoproteins in the central nervous system are involved in the regulation of several neural functions independent of cholesterol metabolism as well as those related to lipid metabolism. We recently demonstrated that lipoproteins are carriers for sphingosine 1-phosphate (S1P). This raised the possibility that S1P mediates the neural cell functions induced by lipoproteins. In the current study, we examined the effects of plasma high-density lipoprotein (HDL) on astroglial cell functions, focusing especially on the role of the lipoprotein-associated S1P. In rat type I astrocytes or C6 glioma cells, similar to S1P, HDL stimulated DNA synthesis and mRNA expression of fibroblast growth factor-2, a potent neurotrophic factor, which was associated with the activation of extracellular signal-regulated kinase (ERK) in a pertussis toxin-sensitive manner. The data from fractionation studies of HDL indicated that S1P may be a major component for the activation of ERK. In C6 glioma cells, HDL also induced phospholipase C-dependent intracellular Ca(2+) mobilization. Desensitization of the C6 glioma cells with S1P abolished these HDL-induced actions. Furthermore, overexpression of S1P receptors in C6 glioma cells led to a significant enhancement of HDL-induced ERK activation and Ca(2+) mobilization. Thus, at least some HDL-induced actions may be mediated by cell-surface S1P receptors in astroglial cells. These results imply that S1P might partially mediate lipoprotein-induced cholesterol metabolism-independent neural cell functions in the central nervous system.