The Role of Aquaporin 1 in Water Retention Mechanism of Arachnoid Cysts: Insights from 3 Case Reports.

BACKGROUND Although arachnoid cysts are common lesions, the pathogenesis of their continuous growth remains unclear. We aimed to identify the role of aquaporins in arachnoid cyst specimens. CASE REPORT We selected 3 cases from our own facility and examined arachnoid cyst wall specimens, which were sampled intraoperatively. Patients presented with variable symptoms, a 52-year-old man with a "heavy sensation" in the head and dysesthesia on the left hand, a 68-year-old man with unsteady gait, and finally a 26-year-old woman with a history of intermittent headaches for 10 years. Intraoperative specimens were obtained and examined. Evaluation techniques were light microscopy, immunohistochemical staining for aquaporin, and electron microscopy. Light microscopy showed that cells were arranged in epithelium-like structures forming several thick lamellae, with visible connective tissue among them. Under electron microscopic examination, cells with many or few cell organelles and with spindle-like nuclei were arranged in lamellar or flattened structures. Many vacuolizations were seen in between. Interdigitation of cells and many desmosomes were observed. All 3 cases were positive for aquaporin 1. CONCLUSIONS Our study showed that water transportation through aquaporin 1 has a potential role in the formation and expansion of arachnoid cysts.

Dexmedetomidine improves excessive extracellular glutamate-induced synaptic depression (BRAINRES-D-21-00941).

We investigated the effects of dexmedetomidine, a selective α2-adrenergic agonist and a sedative, on excessive glutamate-induced depressions of central excitatory synaptic transmissions in vitro. From the CA1 in rat hippocampal slices, orthodromically elicited population spikes (PSs) and field excitatory postsynaptic potentials (fEPSPs) at 0.1 Hz were simultaneously recorded. ANOVA was used for statistics, and p < 0.05 was accepted as significant. Glutamate (10 mM for 10 min) completely depressed PSs and fEPSPs, which were partially recovered by the following washout for 40 min (57.4 ± 10.2% and 59.9 ± 9.8% of the control, respectively, p < 0.01, n = 6). The recoveries in PSs and fEPSPs were improved by pre-treatment and simultaneous treatment with dexmedetomidine (p < 0.01, n = 6) but were not altered by post-treatment. Dexmedetomidine alone did not alter PSs and fEPSPs. Simultaneous treatment with isoproterenol or dobutamine exacerbated the recoveries in PSs and fEPSPs (p < 0.01, n = 6), but simultaneous treatment with salbutamol, propranolol, phenylephrine or phentramine did not influence the recoveries. Simultaneous treatment with AP5 improved the recoveries in PSs and fEPSPs that were depressed by glutamate alone and by glutamate with dexmedetomidine, isoproterenol or dobutamine (p < 0.01, n = 6). Excessive glutamate depresses glutamatergic excitatory synaptic transmissions by mainly mediating NMDA receptors, and the depressed transmissions are improved by α2-adrenoceptor stimulation but are exacerbated by ß1-adrenoceptor stimulation. Dexmedetomidine has a protective effect on neuronal dysfunctions induced by excessive glutamate, which is one of the main mechanisms of the secondary damage in the central nervous system.

Effects of propofol on IPSCs in CA1 and dentate gyrus cells of rat hippocampus: Propofol effects on hippocampal cells' IPSCs.

Propofol (2, 6-diisopropylphenol) is one of the most popular intravenous anesthetic agents. In this study, we compared the effects of propofol on inhibitory postsynaptic currents (IPSCs) induced by single and paired electrical stimulations in CA1 pyramidal cells (CA1-PCs) and dentate gyrus granule cells (DG-GCs) in rat hippocampal slices using the whole cell patch-clamp technique. In the absence of propofol, the amplitude of evoked IPSC by single stimulation and decay time constants were stable in both CA1-PCs and DG-GCs for 30 min. Propofol (1 µM and 10 µM) increased both IPSC amplitude in CA1-PCs, but not in DG-GCs. Further, using a paired pulse stimulation protocol, the ratio of IPSC amplitudes (the second response: A2/the first response: A1) was increased by propofol in CA1, but not in DG-GCs. These results suggest that propofol selectively affects IPSCs in CA1-PCs, which is similar to previously reported actions of benzodiazepines.

Load effect on background rhythms during motor execution: A magnetoencephalographic study.

We investigated the effect of load against self-paced movement on cortical involvement for motor execution. Ten right-handed healthy volunteers were requested to perform brisk extension of the right index finger at self-paced intervals exceeding 10s for three load conditions: 0g, 50g and 100g. Movement-related magnetic fields were recorded using an MEG system. The signals were band-pass-filtered through 18-23Hz and rectified before averaging with respect to EMG onset. We analyzed the time course and %change of peak amplitude with reference to the baseline amplitude in event-related desynchronization (ERD) or synchronization (ERS) in each hemisphere. Maximum response was observed around the left somatomotor area for all conditions. ERD did not show any significant difference before the movement onset among the three load conditions. For %change, ERS in the post-movement period was significantly larger for the 100g load condition than for the 0g load condition, and that was significantly greater over the left than over the right hemisphere. These findings indicate that the load has little effect on pre-movement desynchronization, whereas it affects the post-movement synchronization on background rhythms.

Modulation of alpha activity in the parieto-occipital area by distractors during a visuospatial working memory task: a magnetoencephalographic study.

Oscillatory brain activity is known to play an essential role in information processing in working memory. Recent studies have indicated that alpha activity (8-13 Hz) in the parieto-occipital area is strongly modulated in working memory tasks. However, the function of alpha activity in working memory is open to several interpretations, such that alpha activity may be a direct neural correlate of information processing in working memory or may reflect disengagement from information processing in other brain areas. To examine the functional contribution of alpha activity to visuospatial working memory, we introduced visuospatial distractors during a delay period and examined neural activity from the whole brain using magnetoencephalography. The strength of event-related alpha activity was estimated using the temporal spectral evolution (TSE) method. The results were as follows: (1) an increase of alpha activity during the delay period as indicated by elevated TSE curves was observed in parieto-occipital sensors in both the working memory task and a control task that did not require working memory; and (2) an increase of alpha activity during the delay period was not observed when distractors were presented, although TSE curves were constructed only from correct trials. These results indicate that the increase of alpha activity is not directly related to information processing in working memory but rather reflects the disengagement of attention from the visuospatial input.

Sarpogrelate dilates cerebral arteries in the absence of exogenous serotonin.

Vasoconstriction of arteries induced by serotonin (5-hydroxytryptamine: 5-HT) is mediated by 5-HT2A and 5-HT1B receptors localized on smooth muscle. The present study investigated the impact of sarpogrelate, a 5-HT2A receptor antagonist, on cerebral artery diameter in the presence and absence of exogenous 5-HT. Diameter measurements were obtained in vitro from rabbit cerebral arteries pressurized to 60 mmHg. In the absence of 5-HT, arteries exhibiting pressure-induced myogenic tone dilated to sarpogrelate in a concentration-dependent manner (half maximal inhibitory concentration [IC50] ≈ 2.3 µM). In a separate experimental series, exogenous application of 5-HT (0.01 µM) caused further constriction of myogenically active arteries, decreasing cerebral artery diameter by an additional 25%. In the presence of 5-HT, sarpogrelate caused concentration-dependent vasodilation (IC50 ≈ 2.3 µM) that was similar to that observed in the absence of exogenous 5-HT. Dilation induced by sarpogrelate was not affected by physical removal of the endothelium or inhibition of nitric oxide synthase with Nω-nitro L-arginine. The highest concentration of sarpogrelate (100 µM) induced near maximal dilation, comparable to dilation induced by the L-type voltage-dependent calcium channel antagonist diltiazem. These findings suggest that in rabbit cerebral arteries, sarpogrelate has direct vasodilator effects on vascular smooth muscle.

Oxyhemoglobin-induced suppression of voltage-dependent K+ channels in cerebral arteries by enhanced tyrosine kinase activity.

Cerebral vasospasm following aneurysmal subarachnoid hemorrhage (SAH) has devastating consequences. Oxyhemoglobin (oxyhb) has been implicated in SAH-induced cerebral vasospasm as it causes cerebral artery constriction and increases tyrosine kinase activity. Voltage-dependent, Ca(2+)-selective and K(+)-selective ion channels play an important role in the regulation of cerebral artery diameter and represent potential targets of oxyhb. Here we provide novel evidence that oxyhb selectively decreases 4-aminopyridine sensitive, voltage-dependent K(+) channel (K(v)) currents by approximately 30% in myocytes isolated from rabbit cerebral arteries but did not directly alter the activity of voltage-dependent Ca(2+) channels or large conductance Ca(2+)-activated (BK) channels. A combination of tyrosine kinase inhibitors (tyrphostin AG1478, tyrphostin A23, tyrphostin A25, genistein) abolished both oxyhb-induced suppression of K(v) channel currents and oxyhb-induced constriction of isolated cerebral arteries. The K(v) channel blocker 4-aminopyridine also inhibited oxyhb-induced cerebral artery constriction. The observed oxyhb-induced decrease in K(v) channel activity could represent either channel block, or a decrease in K(v) channel density on the plasma membrane. To explore whether oxyhb altered trafficking of K(v) channels to the plasma membrane, we used an antibody generated against an extracellular epitope of K(v)1.5 channels. In the presence of oxyhb, staining of K(v)1.5 on the plasma membrane surface was markedly reduced. Furthermore, oxyhb caused a loss of spatial distinction between staining with K(v)1.5 and the general anti-phosphotyrosine antibody PY-102. We propose that oxyhb-induced suppression of K(v) currents occurs via a mechanism involving enhanced tyrosine kinase activity and channel endocytosis. This novel mechanism may contribute to oxyhb-induced cerebral artery constriction following SAH.

Emergence of a R-type Ca2+ channel (CaV 2.3) contributes to cerebral artery constriction after subarachnoid hemorrhage.

Cerebral aneurysm rupture and subarachnoid hemorrhage (SAH) inflict disability and death on thousands of individuals each year. In addition to vasospasm in large diameter arteries, enhanced constriction of resistance arteries within the cerebral vasculature may contribute to decreased cerebral blood flow and the development of delayed neurological deficits after SAH. In this study, we provide novel evidence that SAH leads to enhanced Ca2+ entry in myocytes of small diameter cerebral arteries through the emergence of R-type voltage-dependent Ca2+ channels (VDCCs) encoded by the gene CaV 2.3. Using in vitro diameter measurements and patch clamp electrophysiology, we have found that L-type VDCC antagonists abolish cerebral artery constriction and block VDCC currents in cerebral artery myocytes from healthy animals. However, 5 days after the intracisternal injection of blood into rabbits to mimic SAH, cerebral artery constriction and VDCC currents were enhanced and partially resistant to L-type VDCC blockers. Further, SNX-482, a blocker of R-type Ca2+ channels, reduced constriction and membrane currents in cerebral arteries from SAH animals, but was without effect on cerebral arteries of healthy animals. Consistent with our biophysical and functional data, cerebral arteries from healthy animals were found to express only L-type VDCCs (CaV 1.2), whereas after SAH, cerebral arteries were found to express both CaV 1.2 and CaV 2.3. We propose that R-type VDCCs may contribute to enhanced cerebral artery constriction after SAH and may represent a novel therapeutic target in the treatment of neurological deficits after SAH.

Molecular mechanisms of Triple H therapy in the treatment of SAH-induced vasospasm / 第三军医大学学报

Objective Cerebral artery vasospasm is a major cause of death and disability in patients experiencing subarachnoid hemorrhage (SAH). Vasospasm typically has been evaluated using angiography to examine narrowing of large diameter (>1 mm) cerebral arteries. Currently, little is known regarding the impact of SAH on small diameter (100～200 μm) cerebral arteries, which play an important role in the autoregulation of cerebral blood flow. The goal of the current study was to examine the influence of SAH on the pressure-diameter relationship of these small diameter blood vessels. Methods Small diameter cerebral arteries were obtained from a rabbit SAH model. Isolated artery segments were canulated and placed in a myograph chamber superfused with warmed, oxygenated, physiological saline solution. Diameter measurements were then recorded to step-wise increases in intravascular pressure. Results Cerebral arteries from SAH animals exhibited a significant increase in pressure-induced constrictions (myogenic tone) at intravascular pressures between 40 mmHg and 120 mmHg. At intravascular pressures above 120 mmHg, myogenic tone began to decrease and was abolished at pressures above 180 mmHg. Conclusion These data suggest that in the days following SAH, myogenic tone is enhanced in small diameter cerebral arteries subjected to physiological levels of intravascular pressure. However, supra-physiological intravascular pressures causes vasodilation, suggesting small diameter cerebral arteries may act as therapeutic targets of hypervolemia, hemodilution, and hypertension "Triple H therapy" used in the treatment of cerebral artery vasospasm.

Molecular mechanisms of Triple H therapy in the treatment of SAH-induced vasospasm / 第三军医大学学报

Objective Cerebral artery vasospasm is a major cause of death and disability in patients experiencing subarachnoid hemorrhage (SAH). Vasospasm typically has been evaluated using angiography to examine narrowing of large diameter (>1 mm) cerebral arteries. Currently, little is known regarding the impact of SAH on small diameter (100～200 μm) cerebral arteries, which play an important role in the autoregulation of cerebral blood flow. The goal of the current study was to examine the influence of SAH on the pressure-diameter relationship of these small diameter blood vessels. Methods Small diameter cerebral arteries were obtained from a rabbit SAH model. Isolated artery segments were canulated and placed in a myograph chamber superfused with warmed, oxygenated, physiological saline solution. Diameter measurements were then recorded to step-wise increases in intravascular pressure. Results Cerebral arteries from SAH animals exhibited a significant increase in pressure-induced constrictions (myogenic tone) at intravascular pressures between 40 mmHg and 120 mmHg. At intravascular pressures above 120 mmHg, myogenic tone began to decrease and was abolished at pressures above 180 mmHg. Conclusion These data suggest that in the days following SAH, myogenic tone is enhanced in small diameter cerebral arteries subjected to physiological levels of intravascular pressure. However, supra-physiological intravascular pressures causes vasodilation, suggesting small diameter cerebral arteries may act as therapeutic targets of hypervolemia, hemodilution, and hypertension "Triple H therapy" used in the treatment of cerebral artery vasospasm.

Molecular mechanisms of Triple H therapy in the treatment of SAH-induced vasospasm / 第三军医大学学报

Objective Cerebral artery vasospasm is a major cause of death and disability in patients experiencing subarachnoid hemorrhage (SAH). Vasospasm typically has been evaluated using angiography to examine narrowing of large diameter (>1 mm) cerebral arteries. Currently, little is known regarding the impact of SAH on small diameter (100～200 μm) cerebral arteries, which play an important role in the autoregulation of cerebral blood flow. The goal of the current study was to examine the influence of SAH on the pressure-diameter relationship of these small diameter blood vessels. Methods Small diameter cerebral arteries were obtained from a rabbit SAH model. Isolated artery segments were canulated and placed in a myograph chamber superfused with warmed, oxygenated, physiological saline solution. Diameter measurements were then recorded to step-wise increases in intravascular pressure. Results Cerebral arteries from SAH animals exhibited a significant increase in pressure-induced constrictions (myogenic tone) at intravascular pressures between 40 mmHg and 120 mmHg. At intravascular pressures above 120 mmHg, myogenic tone began to decrease and was abolished at pressures above 180 mmHg. Conclusion These data suggest that in the days following SAH, myogenic tone is enhanced in small diameter cerebral arteries subjected to physiological levels of intravascular pressure. However, supra-physiological intravascular pressures causes vasodilation, suggesting small diameter cerebral arteries may act as therapeutic targets of hypervolemia, hemodilution, and hypertension "Triple H therapy" used in the treatment of cerebral artery vasospasm.

Enhanced myogenic tone in cerebral arteries from a rabbit model of subarachnoid hemorrhage.

Cerebral artery vasospasm is a major cause of death and disability in patients experiencing subarachnoid hemorrhage (SAH). Currently, little is known regarding the impact of SAH on small diameter (100-200 microm) cerebral arteries, which play an important role in the autoregulation of cerebral blood flow. With the use of a rabbit SAH model and in vitro video microscopy, cerebral artery diameter was measured in response to elevations in intravascular pressure. Cerebral arteries from SAH animals constricted more (approximately twofold) to pressure within the physiological range of 60-100 mmHg compared with control or sham-operated animals. Pressure-induced constriction (myogenic tone) was also enhanced in arteries from control animals organ cultured in the presence of oxyhemoglobin, an effect independent of the vascular endothelium or nitric oxide synthesis. Finally, arteries from both control and SAH animals dilated as intravascular pressure was elevated above 140 mmHg. This study provides evidence for a role of oxyhemoglobin in impaired autoregulation (i.e., enhanced myogenic tone) in small diameter cerebral arteries during SAH. Furthermore, therapeutic strategies that improve clinical outcome in SAH patients (e.g., supraphysiological intravascular pressure) are effective in dilating small diameter cerebral arteries isolated from SAH animals.