Pretreatment with Clodronate Improved Neurological Function by Preventing Reduction of Posthemorrhagic Cerebral Blood Flow in Experimental Subarachnoid Hemorrhage.

BACKGROUND: Brain perivascular macrophages (PVMs) are potential treatment targets for subarachnoid hemorrhage (SAH), and previous studies revealed that their depletion by clodronate (CLD) improved outcomes after experimental SAH. However, the underlying mechanisms are not well understood. Therefore, we investigated whether reducing PVMs by CLD pretreatment improves SAH prognosis by inhibiting posthemorrhagic impairment of cerebral blood flow (CBF). METHODS: In total, 80 male Sprague-Dawley rats received an intracerebroventricular injection of the vehicle (liposomes) or CLD. Subsequently, the rats were categorized into the prechiasmatic saline injection (sham) and blood injection (SAH) groups after 72 h. We assessed its effects on weak and severe SAH, which were induced by 200- and 300-µL arterial blood injections, respectively. In addition, neurological function at 72 h and CBF changes from before the intervention to 5 min after were assessed in rats after sham/SAH induction as the primary and secondary end points, respectively. RESULTS: CLD significantly reduced PVMs before SAH induction. Although pretreatment with CLD in the weak SAH group provided no additive effects on the primary end point, rats in the severe SAH group showed significant improvement in the rotarod test. In the severe SAH group, CLD inhibited acute reduction of CBF and tended to decrease hypoxia-inducible factor 1α expression. Furthermore, CLD reduced the number of PVMs in rats subjected to sham and SAH surgery, although no effects were observed in oxidative stress and inflammation. CONCLUSIONS: Our study proposes that pretreatment with CLD-targeting PVMs can improve the prognosis of severe SAH through a candidate mechanism of inhibition of posthemorrhagic CBF reduction.

Central sympathetic nerve activation in subarachnoid hemorrhage.

Subarachnoid hemorrhage (SAH) is a life-threatening condition, and although its two main complications-cerebral vasospasm (CVS)/delayed cerebral ischemia (DCI) and early brain injury (EBI)-have been widely studied, prognosis has not improved over time. The sympathetic nerve (SN) system is important for the regulation of cardiovascular function and is closely associated with cerebral vessels and the regulation of cerebral blood flow and cerebrovascular function; thus, excessive SN activation leads to a rapid breakdown of homeostasis in the brain. In the hyperacute phase, patients with SAH can experience possibly lethal conditions that are thought to be associated with SN activation (catecholamine surge)-related arrhythmia, neurogenic pulmonary edema, and irreversible injury to the hypothalamus and brainstem. Although the role of the SN system in SAH has long been investigated and considerable evidence has been collected, the exact pathophysiology remains undetermined, mainly because the relationships between the SN system and SAH are complicated, and many SN-modulating factors are involved. Thus, research concerning these relationships needs to explore novel findings that correlate with the relevant concepts based on past reliable evidence. Here, we explore the role of the central SN (CSN) system in SAH pathophysiology and provide a comprehensive review of the functional CSN network; brain injury in hyperacute phase involving the CSN system; pathophysiological overlap between the CSN system and the two major SAH complications, CVS/DCI and EBI; CSN-modulating factors; and SAH-related extracerebral organ injury. Further studies are warranted to determine the specific roles of the CSN system in the brain injuries associated with SAH.

Variations in the branching patterns of the anterior choroidal artery: an angiographic study with special reference to temporal lobe epilepsy surgery.

BACKGROUND: The preservation of the anterior choroidal artery (AChA) is essential for avoiding neurological sequelae after mesial temporal lobe epilepsy (mTLE) surgery. The purpose of this study is to reveal the anatomical variation in which the perforating branches arise from the plexal segment of the AChA by using a modern neuroimaging modality. METHODS: This study analyzed 3D rotational angiography (3DRA) images from 56 subjects. The AChA and perforating branches were visualized using slab MIP. We analyzed branching patterns, courses of the perforating arteries arising from the plexal segment of the AChA, and the anastomosis of the AChA with other cerebral arteries. RESULTS: The slab MIP applied to 3DRA visualized one or more perforating branches from the AChA in 92.9% of cases. The presence of perforating branches arising from the AChA plexal segment was 17.3%. Most of the branching points of plexal perforators were likely located in the operative field during hippocampal resection. The course of the AChA plexal perforators included the posterior limb of the internal capsule. Anastomosis with other cerebral arteries was visualized in 25% of the AChA with plexal perforators. CONCLUSIONS: 3DRA slab MIP was useful for visualizing the perforating branches of the AChA. Our results showed the possibility that surgical manipulation of the choroid plexus may cause infarction in the AChA territory. We suggest that the existence of the AChA plexal perforators should be recognized to further enhance the safety of hippocampal resection for mTLE.

Palliative lumboperitoneal shunt for leptomeningeal metastasis-related hydrocephalus: A case series.

BACKGROUND: Leptomeningeal metastasis-related hydrocephalus causes distress to patients with end-stage cancer through headache and other symptoms by elevating intracranial pressure, thus reducing quality of life. Ventriculoperitoneal shunt has been used as a treatment option in palliative care. We review four cases of patients who underwent lumboperitoneal shunt for leptomeningeal metastasis-related hydrocephalus. CASES: All patients suffered from severe headache and nausea. The primary lesion was histologically diagnosed as lung adenocarcinoma in each case. The duration from diagnosis to onset of hydrocephalus symptoms ranged from 0 to 52 (mean 26) months. Cerebrospinal fluid pressure in every case was above the normal range due to high intracranial pressure. Case management: Conventional procedures for lumboperitoneal shunt were employed for all patients. Adjustable pressure valves were retrofitted into the shunt system. Case outcome: Three patients demonstrated significant improvement of clinical symptoms and quality of life after placement of lumboperitoneal shunts. In two cases, not only did performance status improve to independent daily activity but also comparatively long-term survival was achieved due to subsequent chemotherapies after surgery. No symptoms of peritoneal dissemination by floating cancer cells in cerebrospinal fluid were seen in any patients. CONCLUSION: Lumboperitoneal shunt appears to improve quality of life if the patient is suffering from symptoms of leptomeningeal metastasis-related hydrocephalus. Compared to ventriculoperitoneal shunt, lumboperitoneal shunt is less invasive and simpler, providing a suitable option for frail patients with end-stage cancer. Adjustable pressure shunt valves can cope with varying symptoms and ventricle sizes.

Perivascular macrophages in cerebrovascular diseases.

Cerebrovascular diseases are a major cause of stroke and dementia, both requiring long-term care. These diseases involve multiple pathophysiologies, with mitochondrial dysfunction being a crucial contributor to the initiation of inflammation, apoptosis, and oxidative stress, resulting in injuries to neurovascular units that include neuronal cell death, endothelial cell death, glial activation, and blood-brain barrier disruption. To maintain brain homeostasis against these pathogenic conditions, brain immune cells, including border-associated macrophages and microglia, play significant roles as brain innate immunity cells in the pathophysiology of cerebrovascular injury. Although microglia have long been recognized as significant contributors to neuroinflammation, attention has recently shifted to border-associated macrophages, such as perivascular macrophages (PVMs), which have been studied based on their crucial roles in the brain. These cells are strategically positioned around the walls of brain vessels, where they mainly perform critical functions, such as perivascular drainage, cerebrovascular flexibility, phagocytic activity, antigen presentation, activation of inflammatory responses, and preservation of blood-brain barrier integrity. Although PVMs act as scavenger and surveillant cells under normal conditions, these cells exert harmful effects under pathological conditions. PVMs detect mitochondrial dysfunction in injured cells and implement pathological changes to regulate brain homeostasis. Therefore, PVMs are promising as they play a significant role in mitochondrial dysfunction and, in turn, disrupt the homeostatic condition. Herein, we summarize the significant roles of PVMs in cerebrovascular diseases, especially ischemic and hemorrhagic stroke and dementia, mainly in correlation with inflammation. A better understanding of the biology and pathobiology of PVMs may lead to new insights on and therapeutic strategies for cerebrovascular diseases.

Persistent brain exposure to high sodium induces stroke onset by upregulation of cerebral microbleeds and oxidative stress in hypertensive rats.

High salt intake induces hypertension and enhances stroke onset. However, whether an increase in brain sodium exposure itself is harmful and has poor prognosis remains unknown. Therefore, we employed hypertensive rats that underwent intracerebroventricular (ICV) infusion of sodium for 28 days and evaluated stroke onset and related cytotoxic brain injuries. Forty-seven spontaneously hypertensive stroke-prone (SHRSP) and 39 normotensive rats (Wistar Kyoto rats [WKY]) underwent persistent ICV infusion of the following four solutions: artificial cerebrospinal fluid, 0.9%, 2.7%, and 9% saline for 28 days. We evaluated stroke onset and all-cause mortality between SHRSP and WKY at each ICV sodium concentration as the primary endpoints. Our secondary objective was to explore histological brain injuries associated with SHRSP induced by high sodium ICV. The results indicated that ICV infusion of 2.7% and 9% sodium showed a significant increase in stroke onset, decrease in body weight, and increase rate of brain water content in SHRSP compared to WKY. Increased blood pressure was not observed for ICV infusion of high sodium, while serum sodium concentration was significantly increased in SHRSP compared to WKY. Histological evaluations revealed that higher sodium infusion significantly increased the number of activated microglia, superoxide, neuronal cell loss, and microbleeds compared to WKY and SHRSP with 0.9% sodium. We conclude that persistent exposure to high sodium in the brain is one of the risk factors for stroke onset upregulating cerebral microbleeds and oxidative stress in hypertensive rats.

Focal motor weakness and recovery following chronic subdural hematoma evacuation.

OBJECTIVE: The incidence of chronic subdural hematomas (cSDHs) is expected to climb precipitously in the coming decades because of the aging populous. Neurological weakness is one of the most common presenting neurological symptoms of cSDH. Yet, the recovery rates of motor strength recovery are seldom documented, as neurological outcomes have predominantly focused on broader functional assessment scores or mortality. In this study, the authors performed one of the first detailed analyses on functional motor weakness and recovery in patients who underwent cSDH evacuation. METHODS: Patients who underwent evacuation of a cSDH at a tertiary academic medical center between November 2013 and December 2021 were retrospectively identified using ICD-9 and ICD-10 billing codes. The presence of focal motor weakness was subcategorized by location as upper extremity (UE) or lower extremity (LE). Postoperative improvement, worsening, or resolution of weakness was recorded at the time of discharge. Statistical analysis included univariate and backward stepwise multivariable logistic regression modeling. RESULTS: A total of 311 patients were included in the analysis. Patients were significantly more likely to experience UE weakness than LE weakness (29% vs 18%, p < 0.001). Forty-one percent (43/104) had both UE and LE weakness present. Risk factors for the development of focal motor weakness at the time of presentation were older age (OR 1.02, p = 0.03), increased cSDH size (OR 1.04, p = 0.02), and the presence of a unilateral cSDH (OR 2.32, p = 0.008). The majority of patients (68%, 71/104) experienced motor strength improvement following cSDH evacuation, with 58% (60/104) having complete resolution of weakness. Multivariable logistic regression analysis revealed that longer symptom duration was associated with lower rates of improvement (OR 0.96, p = 0.024). Older age was also associated with reduced resolution of weakness (OR 0.96, p = 0.02). CONCLUSIONS: This study represents one of the first in-depth analyses investigating the rates of motor strength weakness and recovery following cSDH evacuation. Nearly two-thirds of all patients had complete resolution of their weakness by the time of discharge, and more than three-quarters had partial improvement. Risk factors for impaired neurological recovery were longer symptom duration prior to treatment and older age.

All Three Supersystems-Nervous, Vascular, and Immune-Contribute to the Cortical Infarcts After Subarachnoid Hemorrhage.

The recently published DISCHARGE-1 trial supports the observations of earlier autopsy and neuroimaging studies that almost 70% of all focal brain damage after aneurysmal subarachnoid hemorrhage are anemic infarcts of the cortex, often also affecting the white matter immediately below. The infarcts are not limited by the usual vascular territories. About two-fifths of the ischemic damage occurs within ~ 48 h; the remaining three-fifths are delayed (within ~ 3 weeks). Using neuromonitoring technology in combination with longitudinal neuroimaging, the entire sequence of both early and delayed cortical infarct development after subarachnoid hemorrhage has recently been recorded in patients. Characteristically, cortical infarcts are caused by acute severe vasospastic events, so-called spreading ischemia, triggered by spontaneously occurring spreading depolarization. In locations where a spreading depolarization passes through, cerebral blood flow can drastically drop within a few seconds and remain suppressed for minutes or even hours, often followed by high-amplitude, sustained hyperemia. In spreading depolarization, neurons lead the event, and the other cells of the neurovascular unit (endothelium, vascular smooth muscle, pericytes, astrocytes, microglia, oligodendrocytes) follow. However, dysregulation in cells of all three supersystems-nervous, vascular, and immune-is very likely involved in the dysfunction of the neurovascular unit underlying spreading ischemia. It is assumed that subarachnoid blood, which lies directly on the cortex and enters the parenchyma via glymphatic channels, triggers these dysregulations. This review discusses the neuroglial, neurovascular, and neuroimmunological dysregulations in the context of spreading depolarization and spreading ischemia as critical elements in the pathogenesis of cortical infarcts after subarachnoid hemorrhage.

Vitamin D deficiency promotes intracranial aneurysm rupture.

Intracranial aneurysm rupture causes severe disability and high mortality. Epidemiological studies show a strong association between decreased vitamin D levels and an increase in aneurysm rupture. However, the causality and mechanism remain largely unknown. In this study, we tested whether vitamin D deficiency promotes aneurysm rupture and examined the underlying mechanism for the protective role of vitamin D against the development of aneurysm rupture utilizing a mouse model of intracranial aneurysm. Mice consuming a vitamin D-deficient diet had a higher rupture rate than mice with a regular diet. Vitamin D deficiency increased proinflammatory cytokines in the cerebral arteries. Concurrently, vitamin D receptor knockout mice had a higher rupture rate than the corresponding wild-type littermates. The vitamin D receptors on endothelial and vascular smooth muscle cells, but not on hematopoietic cells, mediated the effect of aneurysm rupture. Our results establish that vitamin D protects against the development of aneurysmal rupture through the vitamin D receptors on vascular endothelial and smooth muscle cells. Vitamin D supplementation may be a viable pharmacologic therapy for preventing aneurysm rupture.

Pharmacological Inhibition of Epidermal Growth Factor Receptor Prevents Intracranial Aneurysm Rupture by Reducing Endoplasmic Reticulum Stress.

BACKGROUND: Multiple pathways and factors are involved in the rupture of intracranial aneurysms. The EGFR (epidermal growth factor receptor) has been shown to mediate inflammatory vascular diseases, including atherosclerosis and aortic aneurysm. However, the role of EGFR in mediating intracranial aneurysm rupture and its underlying mechanisms have yet to be determined. Emerging evidence indicates that endoplasmic reticulum (ER) stress might be the link between EGFR activation and the resultant inflammation. ER stress is strongly implicated in inflammation and apoptosis of vascular smooth muscle cells, both of which are key components of the pathophysiology of aneurysm rupture. Therefore, we hypothesized that EGFR activation promotes aneurysmal rupture by inducing ER stress. METHODS: Using a preclinical mouse model of intracranial aneurysm, we examined the potential roles of EGFR and ER stress in developing aneurysmal rupture. RESULTS: Pharmacological inhibition of EGFR markedly decreased the rupture rate of intracranial aneurysms without altering the formation rate. EGFR inhibition also significantly reduced the mRNA (messenger RNA) expression levels of ER-stress markers and inflammatory cytokines in cerebral arteries. Similarly, ER-stress inhibition also significantly decreased the rupture rate. In contrast, ER-stress induction nullified the protective effect of EGFR inhibition on aneurysm rupture. CONCLUSIONS: Our data suggest that EGFR activation is an upstream event that contributes to aneurysm rupture via the induction of ER stress. Pharmacological inhibition of EGFR or downstream ER stress may be a promising therapeutic strategy for preventing aneurysm rupture and subarachnoid hemorrhage.

A Consideration of Optimal Head Position in Transsylvian Selective Amygdalohippocampectomy.

Transsylvian selective amygdalohippocampectomy (TSA) is one of the predominant surgical options for drug-resistant mesial temporal lobe epilepsy. The purpose of this article is to highlight the unique features of TSA and determine the setting to perform safe and secure TSA with special reference to the optimal head position. TSA should be performed via a small surgical corridor in the temporal stem that contains functionally important fiber tracts, including the uncinate fasciculus, the inferior fronto-occipital fasciculus, and the optic radiation. Graphical simulations proposed that low-degree (<30°) head rotation had the advantage of sufficiently opening the surgical field in TSA and may help surgical procedures within the limited exposure of the medial temporal structures. Inspection of the surgical videos implied that the collapse of the inferior horn was prevented in low-degree rotation, probably because the deformation due to the brain shift was minimized in the medial temporal structures. A simulation also implied that chin-up position had the advantage of resecting the tail of the hippocampus in a straightforward manner. We suggest that the setting is optimized in TSA with low-degree rotation and chin-up head position.

Microscopic observation of morphological changes in cerebral arteries and veins in hyperacute phase after experimental subarachnoid hemorrhage: an in-vivo analysis.

This observational study examined morphological changes in superficial cerebral arteries and veins, which were correlated with increased intracranial pressure (ICP)-dependent and -independent hypoperfusion in hyperacute phase after subarachnoid hemorrhage (SAH). The prechiasmatic injection model was used, and 32 male Sprague-Dawley rats were divided into the sham-operated, saline-injected (V group, ICP increase), and arterial blood-injected (SAH group, subarachnoid blood and plus increase) groups. Morphological changes in cortical arteries and veins were observed through the cranial window with a microscope before and up to 10 min after the injection. At 24 h, the stenotic and obstructive cortical arteries and veins were counted. After 6 min, 60% of rats in the V group showed vasodilatation, whereas all rats in the SAH group demonstrated vasodilation and vasoconstriction (arterial instability) within 10 min. Similar acute venous congestive changes were observed within 10 min in the V and SAH groups. At 24 h, stenotic and obstructive arteries and veins were observed in the SAH group. Neurological deteriorations were observed at 1 h in the V and SAH groups, and at 23 h in the SAH group. The sham-operated group showed no evident vascular changes and neurological deterioration. The same phenomena, including arterial changes after 6 min and immediate venous changes in the V and SAH groups, may have resulted from ICP increase, whereas subarachnoid blood-related factors produced arterial instability within 5 min after blood injection. Subarachnoid blood plays a significant role in hyperacute SAH pathophysiology in addition to ICP increase.

Aneurysmal Inflow Rate Coefficient Predicts Ultra-early Rebleeding in Ruptured Intracranial Aneurysms: Preliminary Report of a Computational Fluid Dynamics Study.

Rebleeding from a ruptured intracranial aneurysm has poor outcomes. Although numerous factors are associated with rebleeding, studies on computational fluid dynamics (CFD) on hemodynamic parameters associated with early rebleeding are scarce. In particular, no report of rebleeding in ultra-early phase exists. We aimed to elucidate the specific hemodynamic parameters associated with ultra-early rebleeding using CFD. In this study, the rebleeding group included patients with aneurysmal subarachnoid hemorrhage (aSAH) that rebled within 6 h from the onset. The control group included patients without rebleeding, observed for >10 h following the initial rupture. Clinical images after initial rupture and before rebleeding were used to build 3D vessel models for hemodynamic analysis focusing on the following parameters: time-averaged wall shear stress (WSS), normalized WSS, low shear area, oscillatory shear index, relative residence time, pressure loss coefficient, and aneurysmal inflow rate coefficient (AIRC). Five and 15 patients in the rebleeding and control groups, respectively, met the inclusion criteria. The World Federation of Neurosurgical Surgeons grade was significantly higher in the rebleeding group (p = 0.0088). Hemodynamic analysis showed significantly higher AIRC in the rebleeding group (p = 0.042). The other parameters were not significantly different between groups. There were no significant differences or correlations between SAH severity and AIRC. AIRC was identified as a hemodynamic parameter associated with ultra-early rebleeding of ruptured intracranial aneurysms. Thus, AIRC calculation may enable the prediction of ultra-early rebleeding.

Inhalational Anesthesia Reduced Transient Neurological Events After Revascularization Surgery for Moyamoya Disease.

BACKGROUND AND OBJECTIVES: The choice between inhalational and total intravenous anesthesia (TIVA) in revascularization surgery for Moyamoya disease (MMD) remains a topic of debate. Anesthesia methods have changed with the advent of new anesthetics. This study investigated whether modern anesthesia methods affected the development of neurological symptoms after revascularization surgery for MMD. METHODS: This single-center retrospective study included 63 adult patients (82 hemispheres) with MMD treated with direct and indirect bypass surgeries at our hospital between 2013 and 2022. Patients were divided into inhalational anesthesia (IA) and TIVA groups based on the anesthesia maintenance method. Baseline patient characteristics; postoperative neurological symptoms, including hyperperfusion syndrome, cerebral infarction, and transient neurological events (TNEs); and cortical hyperintensity belt (CHB) sign scores (5-point scale from 0 to 4) on postoperative magnetic resonance imaging were compared between the two groups. The operation methods, anesthetics, and intraoperative hemodynamic and ventilatory parameters were compared between patients with and without TNEs. RESULTS: The IA and TIVA groups comprised 39 and 43 hemispheres, respectively. The frequency of postoperative hyperperfusion syndrome and cerebral infarction did not differ between the groups, but the number of TNEs in the IA group (5/39; 13%) was significantly lower than that in the TIVA group (16/43; 37%). Multivariate logistic regression analysis revealed that TNEs were associated with TIVA (odds ratio, 3.91; 95% CI, 1.24-12.35; P = .02). The median [IQR] postoperative CHB sign score in the IA group (2 [1-3]) was significantly lower than that in the TIVA group (4 [3-4]). CONCLUSION: The IA group had fewer postoperative TNEs and lower CHB sign scores than the TIVA group. Although further studies are needed, this study provides insights into the prevention of TNEs with IA and reconsideration of the optimal anesthesia for MMD.

Outcome of Superficial Temporal Artery-to-Middle Cerebral Artery Bypass in Appropriately Selected Patients with Acute Ischemic Stroke.

Background: Endovascular treatment is the preferred treatment for acute ischemic stroke (AIS) due to main artery steno-occlusive disease, but it has temporal and technical limitations. Moreover, there is no established treatment for progressive stroke. Superficial temporal artery (STA)-middle cerebral artery (MCA) bypass is sometimes considered as a treatment option. Objective: The objective of this paper is to review the treatment outcomes of patients with AIS undergoing urgent STA-MCA bypass. Methods and Material: This was a retrospective study including 32 patients diagnosed with AIS treated with urgent STA-MCA bypass at our facility. The patients had small infarct volumes and a large diffusion-perfusion mismatch. Results: New ischemic lesions in postoperative diffusion-weighted images were detected in 15 patients (46.9%), but only four (12.5%) developed paralysis. Hyperperfusion occurred in nine patients (28.1%), and five (15.6%) had bypass occlusion at 1 week. Delayed wound healing were found in four patients (12.5%). Neurological outcome was measured 3 months after onset: Manual Muscle Testing (MMT), 3-5 in 27 patients (84.4%); modified Rankin scale (mRS), 0-2 in 17 patients (53.1%); and 0-3 in 26 patients (81.3%). Prognosis was better in patients who underwent surgery after 24 h of stroke onset (mRS, 0-2 in 56.0% cases and 0-3 in 88.0% at 3 months). Statistical analyses revealed that MMT before surgery had a significant association with favorable outcomes (P = 0.041). Conclusions: Urgent STA-MCA bypass for progressive stroke may result in a good prognosis if the right patients are selected and may play an important role in cases treated 24 h after onset in whom endovascular treatment is ineffective.

Loss of body weight in old 5xFAD mice and the alteration of gut microbiota composition.

The cause of age-related body weight loss in Alzheimer's disease (AD) is unclear. We compared the differences in food intake, malabsorption, locomotor activity, and gut microbiota composition between 5xFAD mice, a useful model of AD, and wild-type (WT) mice to investigate the mechanisms underlying lower body weight in 5xFAD mice. Fifteen-month-old male 5xFAD mice and age-matched WT mice were divided into four groups: a control diet (CD) or a high-fat diet (HFD). After feeding CD or HFD for eight to nine weeks, 5xFAD mice had a significantly lower body weight than WT mice regardless of diet (p < 0.05). Additionally, the 5xFAD mice did not show a reduction in food intake compared to the WT mice regardless of diet. To evaluate malabsorption, we performed a fecal fat test. There was no obvious fecal fat in both the 5xFAD mice and WT mice. However, 5xFAD mice showed greater locomotor activity than WT mice in the Y-maze test. The comprehensive analysis of gut microbiota composition showed that 15-month-old 5xFAD mice had more Proteobacteria population and fewer Actinobacteria and Bifidobacteriales populations than WT mice. To investigate the effects of fructooligosaccharides (FOS), we administrated FOS to 15-month-old 5xFAD mice. FOS administration decreased Proteobacteria and increased Actinobacteria population, although that did not change Bifidobacteriales population. Moreover, cognitive impairment and body weight of 5xFAD mice were not changed by FOS administration. In conclusion, loss of body weight in 15-month-old 5xFAD mice might be partially derived from excess energy output by hyperactivity. Moreover, 15-month-old 5xFAD mice might have unique alteration of gut microbiota composition and the potential resistance to FOS.

Identification of the Facial Colliculus in Two-dimensional and Three-dimensional Images.

The facial colliculus (FC), an important landmark for planning a surgical approach to brainstem cavernous malformation (BCM), is a microstructure; therefore, it may be difficult to identify on magnetic resonance imaging (MRI). Three-dimensional (3D) images may improve the FC-identification certainty; hence, this study attempted to validate the FC-identification certainty between two-dimensional (2D) and 3D images of patients with a normal brainstem and those with BCM. In this retrospective study, we included 10 patients with a normal brainstem and 10 patients who underwent surgery for BCM. The region of the FC in 2D and 3D images was independently identified by three neurosurgeons, three times in each case, using the method for continuously distributed test results (0-100). The intra- and inter-rater reliability of the identification certainty were confirmed using the intraclass correlation coefficient (ICC). The FC-identification certainty for 2D and 3D images was compared using the Wilcoxon signed-rank test. The ICC (1,3) and ICC (3,3) in both groups ranged from 0.88 to 0.99; therefore, the intra- and inter-rater reliability were good. In both groups, the FC-identification certainty was significantly higher for 3D images than for 2D images (normal brainstem group; 82.4 vs. 61.5, P = .0020, BCM group; 40.2 vs. 24.6, P = .0059 for the unaffected side, 29.3 vs. 17.3, P = .0020 for the affected side). In the normal brainstem and BCM groups, 3D images had better FC-identification certainty. 3D images are effective for the identification of the FC.

Development of a New Image-Guided Neuronavigation System: Mixed-Reality Projection Mapping Is Accurate and Feasible.

BACKGROUND: Image-guided systems improve the safety, functional outcome, and overall survival of neurosurgery but require extensive equipment. OBJECTIVE: To develop an image-guided surgery system that combines the brain surface photographic texture (BSP-T) captured during surgery with 3-dimensional computer graphics (3DCG) using projection mapping. METHODS: Patients who underwent initial surgery with brain tumors were prospectively enrolled. The texture of the 3DCG (3DCG-T) was obtained from 3DCG under similar conditions as those when capturing the brain surface photographs. The position and orientation at the time of 3DCG-T acquisition were used as the reference. The correct position and orientation of the BSP-T were obtained by aligning the BSP-T with the 3DCG-T using normalized mutual information. The BSP-T was combined with and displayed on the 3DCG using projection mapping. This mixed-reality projection mapping (MRPM) was used prospectively in 15 patients (mean age 46.6 yr, 6 males). The difference between the centerlines of surface blood vessels on the BSP-T and 3DCG constituted the target registration error (TRE) and was measured in 16 fields of the craniotomy area. We also measured the time required for image processing. RESULTS: The TRE was measured at 158 locations in the 15 patients, with an average of 1.19 ± 0.14 mm (mean ± standard error). The average image processing time was 16.58 min. CONCLUSION: Our MRPM method does not require extensive equipment while presenting information of patients' anatomy together with medical images in the same coordinate system. It has the potential to improve patient safety.

Development of Innovative Neurosurgical Operation Support Method Using Mixed-Reality Computer Graphics.

BACKGROUND: In neurosurgery, it is important to inspect the spatial correspondence between the preoperative medical image (virtual space), and the intraoperative findings (real space) to improve the safety of the surgery. Navigation systems and related modalities have been reported as methods for matching this correspondence. However, because of the influence of the brain shift accompanying craniotomy, registration accuracy is reduced. In the present study, to overcome these issues, we developed a spatially accurate registration method of medical fusion 3-dimensional computer graphics and the intraoperative brain surface photograph, and its registration accuracy was measured. METHODS: The subjects included 16 patients with glioma. Nonrigid registration using the landmarks and thin-plate spline methods was performed for the fusion 3-dimensional computer graphics and the intraoperative brain surface photograph, termed mixed-reality computer graphics. Regarding the registration accuracy measurement, the target registration error was measured by two neurosurgeons, with 10 points for each case at the midpoint of the landmarks. RESULTS: The number of target registration error measurement points was 160 in the 16 cases. The target registration error was 0.72 ± 0.04 mm. Aligning the intraoperative brain surface photograph and the fusion 3-dimensional computer graphics required ∼10 minutes on average. The average number of landmarks used for alignment was 24.6. CONCLUSIONS: Mixed-reality computer graphics enabled highly precise spatial alignment between the real space and virtual space. Mixed-reality computer graphics have the potential to improve the safety of the surgery by allowing complementary observation of brain surface photographs and fusion 3-dimensional computer graphics.

Correlation of Inflow Velocity Ratio Detected by Phase Contrast Magnetic Resonance Angiography with the Bleb Color of Unruptured Intracranial Aneurysms.

BACKGROUND: Intraoperative rupture is the most fatal and catastrophic complication of surgery for unruptured intracranial aneurysms (UIAs); thus, it is extremely useful to predict reddish and thin-walled regions of the UIA before surgery. Although several studies have reported a relationship between the hemodynamic characteristics and intracranial aneurysm wall thickness, a consistent opinion is lacking. We aimed to investigate the relationship between objectively and quantitatively evaluated bleb wall color and hemodynamic characteristics using phase-contrast magnetic resonance angiography (PC-MRA). METHODS: Ten patients diagnosed with UIA who underwent surgical clipping and preoperative magnetic resonance imaging along with PC-MRA were included in this study. Bleb wall color was evaluated from an intraoperative video. Based on the Red (R), Green, and Blue values, bleb wall redness (modified R value; mR) was calculated and compared with the hemodynamic characteristics obtained from PC-MRA. RESULTS: The wall redness distribution of 18 blebs in 11 UIAs in 10 patients was analyzed. Bleb/neck inflow velocity ratio (Vb/Va: r = 0.66, P = 0.003) strongly correlated with mR, whereas bleb/neck inflow rate ratio (r = 0.58, P = 0.012) correlated moderately. Multivariate regression analysis revealed that only Vb/Va (P = 0.017) significantly correlated with mR. There was no correlation between wall shear stress and mR. CONCLUSIONS: The bleb redness of UIAs and Vb/Va, calculated using PC-MRA, showed a significantly greater correlation. Thus, it is possible to predict bleb thickness noninvasively before surgery. This will facilitate more detailed pre- and intraoperative strategies for clipping and coiling for safe surgery.