Intraventricular Hemorrhage Growth: Definition, Prevalence and Association with Hematoma Expansion and Prognosis.

BACKGROUND/OBJECTIVES: The objective of this study is to propose a definition of intraventricular hemorrhage (IVH) growth and to investigate whether IVH growth is associated with ICH expansion and functional outcome. METHODS: We performed a prospective observational study of ICH patients between July 2011 and March 2017 in a tertiary hospital. Patients were included if they had a baseline CT scan within 6 h after onset of symptoms and a follow-up CT within 36 h. IVH growth was defined as either any newly occurring intraventricular bleeding on follow-up CT scan in patients without baseline IVH or an increase in IVH volume ≥ 1 mL on follow-up CT scan in patients with initial IVH. Poor outcome was defined as modified Rankin Scale score of 3-6 at 90 days. The association between IVH growth and functional outcome was assessed by using multivariable logistic regression analysis. RESULTS: IVH growth was observed in 59 (19.5%) of 303 patients. Patients with IVH growth had larger baseline hematoma volume, higher NIHSS score and lower GCS score than those without. Of 44 patients who had concurrent IVH growth and hematoma growth, 41 (93.2%) had poor functional outcome at 3-month follow-up. IVH growth (adjusted OR 4.15, 95% CI 1.31-13.20; P = 0.016) was an independent predictor of poor functional outcome (mRS 3-6) at 3 months in multivariable analysis. CONCLUSION: IVH growth is not uncommon and independently predicts poor outcome in ICH patients. It may serve as a promising therapeutic target for intervention.

DLK silencing attenuated neuron apoptosis through JIP3/MA2K7/JNK pathway in early brain injury after SAH in rats.

OBJECTIVE: Dual leucine zipper kinase (DLK/MA3K12) has been reported involved in apoptosis and neuronal degeneration during neural development and traumatic brain injury. This study was designed to investigate the role of DLK with its adaptor protein JNK interacting protein-3 (JIP3), and its downstream MA2K7/JNK signaling pathway in early brain injury (EBI) after subarachnoid hemorrhage (SAH) in a rat model. DESIGN: Controlled in vivo laboratory study. SETTING: Animal research laboratory. SUBJECTS: Two hundred and twenty-three adult male Sprague-Dawley rats weighing 280-320g. INTERVENTIONS: SAH was induced by endovascular perforation in rats. The SAH grade, neurological score, and brain water content were measured at 24 and 72h after SAH. Immunofluorescence staining was used to detect the cells that expressed DLK. The terminal deoxynucleotid transferase-deoxyuridine triphosphate (dUTP) nick end labeling (TUNEL) was used to detect the neuronal apoptosis. In mechanism research, the expression of DLK, JIP3, phosphorylated-JNK (p-JNK)/JNK, and cleaved caspase-3 (CC-3) were analyzed by western blot at 24h after SAH. The DLK small interfering RNA (siRNA), JIP3 siRNA, MA2K7 siRNA and recombinant DLK protein which injected intracerebroventricularly were given as the interventions. MEASUREMENTS AND MAIN RESULTS: The DLK expression was increased in the left cortex neurons and peaked at 24h after SAH. DLK siRNA attenuated brain edema, reduced neuronal apoptosis, and improved the neurobehavioral functions after SAH, but the recombinant DLK protein deteriorated neurobehavioral functions and brain edema. DLK siRNA decreased and recombinant DLK protein increased the expression of MA2K7/p-JNK/CC-3 at 24h after SAH. The JIP3 siRNA reduced the level of JIP3/MA2K7/p-JNK/CC-3, combined DLK siRNA and JIP3 siRNA further decreased the expression of DLK/MA2K7/p-JNK/CC-3, and MA2K7 siRNA lowered the amount of MA2K7/p-JNK/CC-3 at 24h after SAH. CONCLUSIONS: As a negative role, DLK was involved in EBI after SAH, possibly mediated by its adaptor protein JIP3 and MA2K7/JNK signaling pathways. To reduce the level of DLK may be a new target as intervention for SAH.

Naoxueshu Oral Liquid Accelerates Post-Craniotomy Hematoma Absorption in Patients: An Open-Label, Multicenter, and Randomized Controlled Trial.

OBJECTIVE: To investigate whether Naoxueshu Oral Liquid (NXS) could promote hematoma absorption in post-craniotomy hematoma (PCH) patients. METHODS: This is an open-label, multicenter, and randomized controlled trial conducted at 9 hospitals in China. Patients aged 18-80 years with post-craniotomy supratentorial hematoma volume ranging from 10 to 30 mL or post-craniotomy infratentorial hematoma volume less than 10 mL, or intraventricular hemorrhage following cranial surgery were enrolled. They were randomly assigned at a 1:1 ratio to the NXS (10 mL thrice daily for 15 days) or control groups using a randomization code table. Standard medical care was administered in both groups. The primary outcome was the percentage reduction in hematoma volume from day 1 to day 15. The secondary outcomes included the percentage reduction in hematoma volume from day 1 to day 7, the absolute reduction in hematoma volume from day 1 to day 7 and 15, and the change in neurological function from day 1 to day 7 and 15. The safety was closely monitored throughout the study. Moreover, subgroup analysis was performed based on age, gender, history of diabetes, and etiology of intracerebral hemorrhage (ICH). RESULTS: A total of 120 patients were enrolled and randomly assigned between March 30, 2018 and April 15, 2020. One patient was lost to follow-up in the control group. Finally, there were 119 patients (60 in the NXS group and 59 in the control group) included in the analysis. In the full analysis set (FAS) analysis, the NXS group had a greater percentage reduction in hematoma volume from day 1 to day 15 than the control group [median (Q1, Q3): 85% (71%, 97%) vs. 76% (53%, 93%), P<0.05]. The secondary outcomes showed no statistical significance between two groups, either in FAS or per-protocol set (P>0.05). Furthermore, no adverse events were reported during the study. In the FAS analysis, the NXS group exhibited a higher percentage reduction in hematoma volume on day 15 in the following subgroups: male patients, patients younger than 65 years, patients without diabetes, or those with initial cranial surgery due to ICH (all P<0.05). CONCLUSIONS: The administration of NXS demonstrated the potential to promote the percentage reduction in hematoma volume from day 1 to day 15. This intervention was found to be safe and feasible. The response to NXS may be influenced by patient characteristics. (Registration No. ChiCTR1800017981).

Influence of apolipoprotein E and its receptors on cerebral amyloid precursor protein metabolism following traumatic brain injury.

Traumatic brain injury (TBI) is the leading cause of mortality and disability among young individuals in our society, and globally the incidence of TBI is rising sharply. Mounting evidence has indicated that apolipoprotein E (apoE: protein; APOE: gene) genotype influences the outcome after TBI. The proposed mechanism by which APOE affects the clinicopathological consequences of TBI is multifactorial and includes amyloid deposition, disruption of lipid distribution, dysfunction of mitochondrial energy production, oxidative stress and increases intracellular calcium in response to injury. This paper reviews the current state of knowledge regarding the influence of apoE and its receptors on cerebral amyloid beta-protein precursor metabolism following TBI.

Essential role of MALAT1 in reducing traumatic brain injury.

As a highly evolutionary conserved long non-coding RNA, metastasis associated lung adenocarcinoma transcript 1 (MALAT1) was first demonstrated to be related to lung tumor metastasis by promoting angiogenesis. To investigate the role of MALAT1 in traumatic brain injury, we established mouse models of controlled cortical impact and cell models of oxygen-glucose deprivation to mimic traumatic brain injury in vitro and in vivo. The results revealed that MALAT1 silencing in vitro inhibited endothelial cell viability and tube formation but increased migration. In MALAT1-deficient mice, endothelial cell proliferation in the injured cortex, functional vessel density and cerebral blood flow were reduced. Bioinformatic analyses and RNA pull-down assays validated enhancer of zeste homolog 2 (EZH2) as a downstream factor of MALAT1 in endothelial cells. Jagged-1, the Notch homolog 1 (NOTCH1) agonist, reversed the MALAT1 deficiency-mediated impairment of angiogenesis. Taken together, our results suggest that MALAT1 controls the key processes of angiogenesis following traumatic brain injury in an EZH2/NOTCH1-dependent manner.

Downregulation of miR-491-5p promotes neovascularization after traumatic brain injury.

MicroRNA-491-5p (miR-491-5p) plays an important role in regulating cell proliferation and migration; however, the effect of miR-491-5p on neovascularization after traumatic brain injury remains poorly understood. In this study, a controlled cortical injury model in C57BL/6 mice and an oxygen-glucose deprivation model in microvascular endothelial cells derived from mouse brain were established to simulate traumatic brain injury in vivo and in vitro, respectively. In the in vivo model, quantitative real-time-polymerase chain reaction results showed that the expression of miR-491-5p increased or decreased following the intracerebroventricular injection of an miR-491-5p agomir or antagomir, respectively, and the expression of miR-491-5p decreased slightly after traumatic brain injury. To detect the neuroprotective effects of miR-491-p, neurological severity scores, Morris water maze test, laser speckle techniques, and immunofluorescence staining were assessed, and the results revealed that miR-491-5p downregulation alleviated neurological dysfunction, promoted the recovery of regional cerebral blood flow, increased the number of lectin-stained microvessels, and increased the survival of neurons after traumatic brain injury. During the in vitro experiments, the potential mechanism of miR-491-5p on neovascularization was explored through quantitative real-time-polymerase chain reaction, which showed that miR-491-5p expression increased or decreased in brain microvascular endothelial cells after transfection with an miR-491-5p mimic or inhibitor, respectively. Dual-luciferase reporter and western blot assays verified that metallothionein-2 was a target gene for miR-491-5p. Cell counting kit 8 (CCK-8) assay, flow cytometry, and 2?,7?-dichlorofluorescein diacetate (DCFH-DA) assay results confirmed that the downregulation of miR-491-5p increased brain microvascular endothelial cell viability, reduced cell apoptosis, and alleviated oxidative stress under oxygen-glucose deprivation conditions. Cell scratch assay, Transwell assay, tube formation assay, and western blot assay results demonstrated that miR-491-5p downregulation promoted the migration, proliferation, and tube formation of brain microvascular endothelial cells through a metallothionein-2-dependent hypoxia-inducible factor-1α/vascular endothelial growth factor pathway. These findings confirmed that miR-491-5p downregulation promotes neovascularization, restores cerebral blood flow, and improves the recovery of neurological function after traumatic brain injury. The mechanism may be mediated through a metallothionein-2-dependent hypoxia-inducible factor-1α/vascular endothelial growth factor signaling pathway and the alleviation of oxidative stress. All procedures were approved by Ethics Committee of the First Affiliated Hospital of Chongqing Medical University, China (approval No. 2020-304) on June 22, 2020.

Neat1 decreases neuronal apoptosis after oxygen and glucose deprivation.

Studies have shown that downregulation of nuclear-enriched autosomal transcript 1 (Neat1) may adversely affect the recovery of nerve function and the increased loss of hippocampal neurons in mice. Whether Neat1 has protective or inhibitory effects on neuronal cell apoptosis after secondary brain injury remains unclear. Therefore, the effects of Neat1 on neuronal apoptosis were observed. C57BL/6 primary neurons were obtained from the cortices of newborn mice and cultured in vitro, and an oxygen and glucose deprivation cell model was established to simulate the secondary brain injury that occurs after traumatic brain injury in vitro. The level of Neat1 expression in neuronal cells was regulated by constructing a recombinant adenovirus to infect neurons, and the effects of Neat1 expression on neuronal apoptosis after oxygen and glucose deprivation were observed. The experiment was divided into four groups: the control group, without any treatment, received normal culture; the oxygen and glucose deprivation group were subjected to the oxygen and glucose deprivation model protocol; the Neat1 overexpression and Neat1 downregulation groups were treated with Neat1 expression intervention techniques and were subjected to the in oxygen and glucose deprivation protocol. The protein expression levels of neurons p53-induced death domain protein 1 (PIDD1, a pro-apoptotic protein), caspase-2 (an apoptotic priming protein), cytochrome C (a pro-apoptotic protein), and cleaved caspase-3 (an apoptotic executive protein) were measured in each group using the western blot assay. To observe changes in the intracellular distribution of cytochrome C, the expression levels of cytochrome C in the cytoplasm and mitochondria of neurons from each group were detected by western blot assay. Differences in the cell viability and apoptosis rate between groups were detected by cell-counting kit 8 assay and terminal deoxynucleotidyl transferase dUTP nick-end labeling assay, respectively. The results showed that the apoptosis rate, PIDD1, caspase-2, and cleaved caspase-3 expression levels significantly decreased, and cell viability significantly improved in the Neat1 overexpression group compared with the oxygen and glucose deprivation group; however, Neat1 downregulation reversed these changes. Compared with the Neat1 downregulation group, the cytosolic cytochrome C level in the Neat1 overexpression group significantly decreased, and the mitochondrial cytochrome C level significantly increased. These data indicate that Neat1 upregulation can reduce the release of cytochrome C from the mitochondria to the cytoplasm by inhibiting the PIDD1-caspase-2 pathway, reducing the activation of caspase-3, and preventing neuronal apoptosis after oxygen and glucose deprivation, which might reduce secondary brain injury after traumatic brain injury. All experiments were approved by the Animal Ethics Committee of the First Affiliated Hospital of Chongqing Medical University, China, on December 19, 2020 (approval No. 2020-895).

Mechanisms of early brain injury after SAH: matrix metalloproteinase 9.

Subarachnoid hemorrhage (SAH) is an important cause of death and disability worldwide. To date, there is not a definitive treatment that completely prevents brain injury after SAH. Recently, early brain injury (EBI) has been pointed out to be the primary cause of mortality in SAH patients. Apoptosis that occurs in neuronal tissues and cerebral vasculature after SAH plays an essential role in EBI. Matrix metalloproteinase 9 (MMP-9) has been found to increase in many cerebral vascular diseases. There have been reports that MMP-9 can mediate apoptosis, which called anoikis in cerebral ischemia models, through cleaving main components of the extracellular matrix (ECM), especially laminin. Therefore, minocycline, which has been found to inhibit MMP-9, may be protective to brain injury after SAH. We based our hypothesis on the fact that SAH possesses some aspects that are similar to those of cerebral ischemia. It is conceivable that MMP-9 may also be involved in the pathological process of EBI after SAH, and minocycline can relieve anoikis and improve EBI after SAH.

The role of apolipoprotein e in the pathological events following subarachnoid hemorrhage: a review.

Subarachnoid hemorrhage (SAH) strikes individuals with devastating neurological results. Traditional viewpoints do not explain all the differences that are usually found in clinical practice. The role of genetic predisposition in SAH has recently been investigated. Particular attention has been paid to the apolipoprotein E (apoE) genotype. APOE genotype is a major prognostic factor in patient outcome after spontaneous aneurysmal SAH. In patients with SAH, the expression of the apoE ε4 allele is associated with a higher risk of negative outcome and delayed ischemia. Evidence from experimental and clinical studies confirms that apoE plays an important role in the pathological events after SAH. This article reviews related research and surveys the links between the pathological events of SAH and apoE.

Association of APOE polymorphism with the change of brain function in the early stage of aneurysmal subarachnoid hemorrhage.

Recent studies have indicated that early brain injury may be responsible for the detrimental effects seen in patients after subarachnoid hemorrhage (SAH). In this study, we investigated the relationship between apolipoprotein E gene (APOE) polymorphism and the change of brain function in the early stage of aneurysmal SAH. A total of 79 patients admitted within 5 days after aneurysmal SAH were recruited in the study. Patient characteristics, such as age, gender, Fisher and Hunt-Hess grade were collected when admitted. Electroencephalogram (EEG) was recorded on admission and at 3-5 days after onset to assess the change of brain function of the patients in acute stage of SAH. The result of the second EEG recording was defined as EEG deterioration if the decrease in alpha wave frequency, increase in slow wave or decline in amplitude were observed when compared with the first EEG recording. The APOE polymorphism was determined in all patients by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Ten of 17 patients with APOEε4 (58.8%) showed the deteriorated EEGs, which was significantly different from those without APOEε4 (18 of 62 patients, 29.0%, p=0.023). However, neither the presence of ε2 nor of ε3 was significantly different from those absent of it (p>0.05). Univariate logistic regression analyses showed that both high Fisher grade (p=0.028, OR=2.917, 95% CI=1.124-7.572) and APOEε4 (p=0.027, OR=3.492, 95% CI=1.150-10.604) were risk factors to EEG aggravation after aneurysmal SAH. The association of APOEε4 for deteriorated EEG was more significant after adjustment for age, gender, Hunt-Hess grade on admission, and Fisher grade (p=0.007, OR=5.741, 95% CI=1.625-20.280). Our findings suggest that APOEε4 allele is a risk factor to brain function aggravation in the early stage of aneurysmal SAH, and it may contribute to early brain injury after SAH.

Protection of minocycline on early brain injury after subarachnoid hemorrhage in rats.

Minocycline has been shown to be neuroprotective in cerebral ischemia and in other models of brain injury. Our goal is to observe the protection of minocycline on EBI after SAH and the mechanism. 48 adult male SD rats were randomly divided into four groups: the sham-operated group, SAH group, vehicle group (SAH+normal sodium), and minocycline group (SAH+minocycline). The SAH model was induced by injecting 300 µl of autologous arterial blood into the prechiasmatic cistern. Expressions of MMP-9 in the hippocampus were examined at 24 h by western blot and zymography. Western blot and zymography showed that the expression of total and active MMP-9 increased dramatically at 24 h after SAH compared with that of the sham group (P<0.01). The clinical assessments got a lower score than that of the sham-operated group. After treated with minocycline, the expression of MMP-9 decreased significantly (P<0.01 vs. vehicle group), and the clinical assessments improved. We conclude that minocycline can protect EBI after SAH, which may be related to the mechanism of inhibiting the expression of MMP-9 in the hippocampus.

Association of apolipoprotein E polymorphisms with cerebral vasospasm after spontaneous subarachnoid hemorrhage.

Cerebral vasospasm (CVS) is the main complication of spontaneous subarachnoid hemorrhage (SAH), severely affecting clinical outcome of patients with SAH. Apolipoprotein E gene (APOE) is associated with prognosis of spontaneous subarachnoid hemorrhage (SAH), and APOEε4 allele is reported to be apt to CVS after SAH. The current study aimed to investigate the association of APOE polymorphisms with CVS after SAH. One hundred and eighty-five patients with spontaneous SAH were recruited in the study. APOE genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). CVS was judged by Transcranial Doppler sonography (TCD) combined with patients' condition. χ2-test and logistic regression analysis were done by SPSS (version 11.5). The distributions of APOE genotypes and alleles matched Hardy-Weinberg Law. In 185 patients, 21 of 32 (65.7%) patients with APOEε4 allele showed CVS, which was significantly different from those without APOE ε4 allele (56 of 153 patients, 36.6%, P=0.022). However, neither the presence of ε2 nor ε3 was significantly different from those absent of it (P>0.05). Logistic regression analysis demonstrated that ApoEε4 allele was a risk factor (OR=2.842. 95% CI 1.072-6.124. P=0.019) to predispose to CVS after adjusting for age, sex, hypertension or not, hyperlipemia or not, Fisher grade, and Hunt-Hess grade after SAH. Our finding suggests that the patients with APOEε4 allele predispose to CVS after spontaneous SAH.

Clinical study of changes of cerebral microcirculation in cerebral vasospasm after SAH.

Aim to investigate the changes of cerebral microcirculation after subarachnoid hemorrhage (SAH) and its association with cerebral vasospasm (CVS) after SAH. CTP was performed in 85 patients with SAH and 35 controls. Cerebral blood flow (CBF), cerebral blood volume (CBV) and mean transit time (MTT) were recorded for final analysis. CTP parameters were compared between (1) SAH group and control group, (2) CVS group and non-CVS group (nCVS), (3) symptomatic CVS (sCVS) group and asymptomatic CVS (asCVS) group. Compared to control group, there were significant differences in CBF and MTT of SAH patients (P<0.05). Among SAH patients, the CBF and MTT (a decreased CBF and a prolonged MTT) of CVS patients were significantly different from those of non-CVS patients (P<0.05). In 46 CVS patients, sCVS group presented significantly lower CBF and more prolonged MTT than asCVS patients (P<0.05). Seven cases with MTT between 6.31 and 12.72 s showed delayed ischemic neurological deficit (DIND), two of whom had hemiplegia, and one died. Our findings suggest that CTP examination contributes to uncover the changes of cerebral microcirculation after SAH, and the changes of cerebral microcirculation are associated with CVS post SAH.

Objective evaluation of the treatment methods of intracranial aneurysm surgery.

OBJECTIVE: this study evaluated the clinical value of craniotomy and intravascular embotherapy in the treatment of intracranial aneurysms. METHODS: The clinical data of 126 cases of intracranial aneurysms from July 2008 to July 2009 was analyzed retrospectively, 86 cases of all were clipped and other 40 cases were coiled. RESULTS: in 86 cases with craniotomy (according to Hunt-Hess classification, 71 cases belong to grade I-III and 15 cases belong to grade IV-V), 1 case died, 3 cases recovered with serious nervous system symptoms, 9 cases recovered with Mild neurological symptoms, and the remaining 73 cases recovered with normal life and work. In 40 cases with intravascular embotherapy (according to Hunt-Hess classification, 33 cases belong to grade I-III and 7 cases belong to grade IV-V), 2 cases recovered with serious nervous system symptoms, 5 cases recovered with mild neurological symptoms, the remaining 33 cases recovered with normal life and work; no death case. CONCLUSIONS: the situation is different in patients according to aneurysm size, shape, and location; if treatment for intracranial aneurysms is to achieve a satisfactory effect, two treatments must complement each other.

Matrix metalloproteinase 9 inhibition reduces early brain injury in cortex after subarachnoid hemorrhage.

This study investigated the role of matrix metalloproteinase-9 (MMP-9) in early brain injury (EBI) after subarachnoid hemorrhage (SAH). Sprague-Dawley male rats (n=30) between 250 and 300 g were used. SAH was produced by injecting autologous arterial blood into the prechiasmatic cistern. SB-3CT, a selective MMP-9 inhibitor, was injected intraperitoneally after SAH induction. MMP-9 protein expression was measured by western blot; laminin expression and neuronal cells in the cerebral cortex were studied by immunohistochemistry and TUNEL staining at 24h after SAH. MMP-9 expression was increased after SAH and decreased by SB-3CT inhibition at 24h after SAH (P<0.01). Laminin, the substrate of MMP-9, was decreased at 24h after SAH, and SB-3CT prevented laminin degradation. The number of TUNEL-positive neurons in cerebral cortex was increased after SAH and decreased by SB-3CT (P<0.01). MMP-9 may be involved in EBI after SAH and inhibition of MMP-9 may reduce EBI in cerebral cortex.

Delayed intracranial hemorrhage associated with antiplatelet therapy in stent-assisted coil embolized cerebral aneurysms.

Administration of oral clopidogrel plus aspirin is the most important regimen to reduce thromboembolic complications in stent-assisted coil embolization of cerebral aneurysm. However, such therapy may increase the risk of hemorrhage. The purpose of this study is to analyze the effect of two different antiplatelet regimens on hemorrhagic and thromboembolic complication rates around the stent-assisted coil embolization period. Records over a 2-year period were reviewed in a retrospective cohort study. For 49 consecutive stent-assisted coil embolization procedures over 41 patients, nine patients received routine antiplatelet drugs (300 mg aspirin and 75 mg clopidogrel) for 3 days before embolization, and 32 received a loading dose of antiplatelet drugs (300 mg aspirin and 300 mg clopidogrel) just before induction of anesthesia. Delayed intracerebral hemorrhage (DIH) was observed more often in the routine antiplatelet group (2/9 cases, 22.2%) in comparison with the loading group (0/32 cases, 0%; P = 0.044; Fisher exact test). The two hemorrhagic cases were both female, and occurred within 24 h of postembolization. The thromboembolic complication rates were not significantly different between the two groups. Oral administration of routine antiplatelet drugs for 3 days before stent-assisted coil embolization possibly increases the risk of delayed intracranial hemorrhage, compared to loading group. Symptomatic thromboembolic complications have no significant difference in the two different regimens.

Value of noninvasive imaging in follow-up of intracranial aneurysm.

Follow-up is necessary for treated and untreated aneurysms. The purpose of this study is to assess the results of treated aneurysms, the development of untreated aneurysms and the incidence of new aneurysms through short-term follow-up with noninvasive imaging, including CTA and MRA. More-than-once follow-up imaging with either CTA or MRA was performed in 73 patients, 65 of them suffering SAH. CTA was performed in 46 patients with clipped aneurysms, 9 patients with coiled aneurysms and 8 cases with untreated aneurysms. MRA was performed in ten patients with coiled aneurysms. CTA follow-up demonstrated that in 48 clipped aneurysms, 47 aneurysms completely disappeared; one aneurysm with neck remnant and one new aneurysm was found. No recurrence was found after microsurgical clipping. CTA follow-up provided limited information for ten coiled aneurysms because of poor quality images due to artifacts from coil. MRA follow-up of 12 coiled aneurysms showed there were no recanalization, recurrence or new aneurysm. In 20 untreated aneurysms, 19 stayed unchanged, and one aneurysm automatically disappeared. The newest generation of CTA and MRA can be used for following-up of intracranial aneurysms, and is more readily accepted by Chinese patients because of convenience, non-invasiveness and low price.

Hypoperfusion assessed by pressure reactivity index is associated with delayed cerebral ischemia after subarachnoid hemorrhage: an observational study.

BACKGROUND: Dysfunction of cerebral autoregulation is one of the pathophysiological mechanisms that causes delayed cerebral ischemia (DCI) after subarachnoid hemorrhage (SAH). Pressure reactivity index (PRx) have been confirmed to reflect the level of cerebral autoregulation and used to derive optimal cerebral perfusion pressure (CPPopt). The goal of this study is to explore the associations between autoregulation, CPPopt, PRx, and DCI. METHODS: Continuous intracranial pressure (ICP), arterial blood pressure (ABP), and cerebral perfusion pressure (CPP) signals acquired from 61 aSAH patients were retrospectively analyzed. PRx was calculated and collected by Pneumatic computer system. The CPP at the lowest PRx was determined as the CPPopt. The duration of a hypoperfusion event (dHP) was defined as the cumulative time that the PRx was > 0.3 and the CPP was

Atorvastatin combined with dexamethasone in chronic subdural haematoma (ATOCH II): study protocol for a randomized controlled trial.

BACKGROUND: Chronic subdural haematoma (CSDH) is a common condition in the elderly that often requires neurosurgical management. For small CSDH, evidence has emerged that statins may reduce haematoma volume and improve outcomes, presumably by reducing local inflammation and promoting vascular repair. We wish to extend this evidence in a study that aims to determine the efficacy and safety of atorvastatin combined with low-dose dexamethasone in patients with CSDH. METHODS: The second ATorvastatin On Chronic subdural Hematoma (ATOCH-II) study is a multi-centre, randomized, placebo-controlled, double-blind trial which aims to enrol 240 adult patients with a conservative therapeutic indication for CSDH, randomly allocated to standard treatment with atorvastatin 20 mg combined with low-dose dexamethasone (or matching placebos) daily for 28 days, and with 152 days of follow-up. The primary outcome is a composite good outcome defined by any reduction from baseline in haematoma volume and survival free of surgery at 28 days. Secondary outcomes include functional outcome on the modified Rankin scale (mRS) and modified Barthel Index at 28 days, surgical transition and reduction in haematoma volumes at 14, 28 and 90 days. DISCUSSION: This multi-centre clinical trial aims to provide high-quality evidence on the efficacy and safety of the combined treatment of atorvastatin and low-dose dexamethasone to reduce inflammation and enhance angiogenesis in CSDH. TRIAL REGISTRATION: ChiCTR, ChiCTR1900021659 . Registered on 3 March 2019, http://www.chictr.org.cn/showproj.aspx?proj=36157 .

Targeting CCL20 inhibits subarachnoid hemorrhage-related neuroinflammation in mice.

Recent evidence suggests that CC chemokine ligand 20 (CCL20) is upregulated after subarachnoid hemorrhage (SAH). Here, we investigated the functions of CCL20 in SAH injury and its underlying mechanisms of action. We found that CCL20 is upregulated in an SAH mouse model and in cultured primary microglia and neurons. CCL20-neutralizing antibody alleviated SAH-induced neurological deficits, decreased brain water content and neuronal apoptosis, and repressed microglial activation. We observed increased levels of CCL20, CC chemokine receptor 6 (CCR6), interleukin 1 beta (IL-1ß), and tumor necrosis factor alpha (TNF-α), as well as of microglial activation in microglia treated with oxyhemoglobin (OxyHb). CCL20 or CCR6 knockdown reversed the effects of OxyHb on microglia. Conditioned medium from OxyHb-treated microglia induced neuronal apoptosis, while the percentage of apoptotic neurons in the conditioned medium from microglia transfected with CCL20 siRNA or CCR6 siRNA was decreased. We observed no decrease in OxyHb-induced apoptosis in CCL20-knockdown neurons. Conditioned medium from OxyHb-treated neurons led to microglial activation and induced CCR6, IL-1ß and TNF-α expression, while CCL20 knockdown in neurons or CCR6 knockdown in microglia reversed those effects. Our results thus suggest CCL20 may be targeted to elicit therapeutic benefits after SAH injury.