The novel imaging methods in diagnosis and assessment of cerebrovascular diseases: an overview.

Cerebrovascular diseases, including ischemic strokes, hemorrhagic strokes, and vascular malformations, are major causes of morbidity and mortality worldwide. The advancements in neuroimaging techniques have revolutionized the field of cerebrovascular disease diagnosis and assessment. This comprehensive review aims to provide a detailed analysis of the novel imaging methods used in the diagnosis and assessment of cerebrovascular diseases. We discuss the applications of various imaging modalities, such as computed tomography (CT), magnetic resonance imaging (MRI), positron emission tomography (PET), and angiography, highlighting their strengths and limitations. Furthermore, we delve into the emerging imaging techniques, including perfusion imaging, diffusion tensor imaging (DTI), and molecular imaging, exploring their potential contributions to the field. Understanding these novel imaging methods is necessary for accurate diagnosis, effective treatment planning, and monitoring the progression of cerebrovascular diseases.

Endothelial TREM-1 receptor regulates the blood-brain barrier integrity after intracerebral hemorrhage in mice via SYK/ß-catenin signaling.

BACKGROUND: Intracerebral hemorrhage (ICH) is a high mortality and disability stroke subtype. Destruction of the blood-brain barrier (BBB) is a crucial contributor to brain edema and neurological deficit after ICH. Triggering receptor expressed on myeloid cells 1 (TREM-1) has been reported to be expressed in endothelial cells, but its role in ICH remains unclear. This study aims to evaluate the role of TREM-1 on BBB permeability after ICH in mice. METHODS: Two hundred and forty-two CD1 mice were used in this study. The ICH model was established by collagenase injection. LP17 was administered intranasally at 2 or 8 h after ICH to inhibit TREM-1. To explore the underlying mechanism, SYK activation CRISPR was administered intracerebroventricularly with LP17, and Anti-mouse TREM-1 rat IgG2a (a specific TREM-1 agonist) was injected intracerebroventricularly with R406 (a specific SYK inhibitor) intraperitoneally. Neurobehavioral outcome, brain water content, BBB permeability, and protein expression were evaluated. RESULTS: The expression level of the TREM-1 receptor increased rapidly as early as 6 h after ICH, and it was mainly expressed on the endotheliocytes in the neurovascular unit. Early and delayed administration of LP17 significantly decreased brain edema and improved neurobehavioral outcomes at 24 h after ICH. LP17 reduced the BBB permeability by increasing ß-catenin, claudin-5 and ZO-1 expression. Furthermore, SYK activation CRISPR abolished the beneficial effect of LP17 on the expression of the above junction molecules. Meanwhile, R406 reversed the impact of the TREM-1 activator on the downregulation of ß-catenin, claudin-5 and ZO-1 expression. CONCLUSIONS: This study demonstrated that TREM-1 deteriorated BBB permeability via modulating the expression of interendothelial junction molecules after ICH, and this regulation is partly mediated by the SYK/ß-catenin signaling pathway.

Emerging diagnostic markers and therapeutic targets in post-stroke hemorrhagic transformation and brain edema.

Stroke is a devastating condition that can lead to significant morbidity and mortality. The aftermath of a stroke, particularly hemorrhagic transformation (HT) and brain edema, can significantly impact the prognosis of patients. Early detection and effective management of these complications are crucial for improving outcomes in stroke patients. This review highlights the emerging diagnostic markers and therapeutic targets including claudin, occludin, zonula occluden, s100ß, albumin, MMP-9, MMP-2, MMP-12, IL-1ß, TNF-α, IL-6, IFN-γ, TGF-ß, IL-10, IL-4, IL-13, MCP-1/CCL2, CXCL2, CXCL8, CXCL12, CCL5, CX3CL1, ICAM-1, VCAM-1, P-selectin, E-selectin, PECAM-1/CD31, JAMs, HMGB1, vWF, VEGF, ROS, NAC, and AQP4. The clinical significance and implications of these biomarkers were also discussed.

Kynurenine/Aryl Hydrocarbon Receptor Modulates Mitochondria-Mediated Oxidative Stress and Neuronal Apoptosis in Experimental Intracerebral Hemorrhage.

Aims: Oxidative stress and neuronal apoptosis play crucial roles in the pathological processes of secondary injury after intracerebral hemorrhage (ICH). Aryl hydrocarbon receptor (AHR), together with its endogenous ligand kynurenine, is known to mediate free radical accumulation and neuronal excitotoxicity in central nervous systems. Herein, we investigate the pathological roles of kynurenine/AHR after ICH. Results: Endogenous AHR knockout alleviated reactive oxygen species accumulation and neuronal apoptosis in ipsilateral hemisphere at 48 h after ICH in mice. The ICH insult resulted in an increase of total and nucleus AHR protein levels and AHR transcriptional activity. Inhibition of AHR provided both short- and long- term neurological benefits by attenuating mitochondria-mediated oxidative stress and neuronal apoptosis after ICH in mice. RhoA-Bax signaling activated mitochondrial death pathway and participated in deleterious actions of AHR. Finally, we reported that exogenous kynurenine aggravated AHR activation and mediated the brain mentioned earlier. Male animals were used in the experiments. Innovation: We show for the first time that kynurenine/AHR mediates mitochondria death and free radical accumulation, at least partially via the RhoA/Bax signaling pathway. Pharmacological antagonists of AHR and kynurenine may ameliorate neurobehavioral function and improve the prognosis of patients with ICH. Conclusion: Kynurenine/AHR may serve as a potential therapeutic target to attenuate mitochondria-mediated oxidative stress and neuronal cells impairment in patients with ICH. Antioxid. Redox Signal. 37, 1111-1129.

Inhibition of caspase-1-mediated inflammasome activation reduced blood coagulation in cerebrospinal fluid after subarachnoid haemorrhage.

BACKGROUND: Neuroinflammation and blood coagulation responses in cerebrospinal fluid (CSF) contribute to the poor outcome associated with subarachnoid haemorrhage (SAH). We explored the role of caspase-1-mediated inflammasome activation on extrinsic blood coagulation in CSF after SAH. METHODS: Post-SAH proteomic changes and correlation between caspase-1 with extrinsic coagulation factors in human CSF after SAH were analysed. Time course and cell localisation of brain inflammasome and extrinsic coagulation proteins after SAH were explored in a rat SAH model. Pharmacological inhibition of caspase-1 via VX-765 was used to explore the role of caspase-1 in blood clearance and CSF circulation after SAH in rats. Primary astrocytes were used to evaluate the role of caspase-1 in haemoglobin-induced pyroptosis and tissue factor (TF) production/release. FINDINGS: Neuroinflammation and blood coagulation activated after SAH in human CSF. The caspase-1 levels significantly correlated with the extrinsic coagulation factors. The activated caspase-1 and extrinsic coagulation initiator TF was increased on astrocytes after SAH in rats. VX-765 attenuated neurological deficits by accelerating CSF circulation and blood clearance through inhibiting pyroptotic neuroinflammation and TF-induced fibrin deposition in the short-term, and improved learning and memory capacity by preventing hippocampal neuronal loss and hydrocephalus in the long-term after SAH in rats. VX-765 reduced haemoglobin-induced pyroptosis and TF production/release in primary astrocytes. INTERPRETATION: Inhibition of caspase-1 by VX-765 appears to be a potential treatment against neuroinflammation and blood coagulation in CSF after SAH. FUNDING: This study was supported by National Institutes of Health of United States of America, and National Natural Science Foundation of China.

Inhibition of Aryl Hydrocarbon Receptor Attenuates Hyperglycemia-Induced Hematoma Expansion in an Intracerebral Hemorrhage Mouse Model.

Background Hyperglycemia is associated with greater hematoma expansion (HE) and worse clinical prognosis after intracerebral hemorrhage (ICH). However, the clinical benefits of intensive glucose normalization remain controversial, and there are no approved therapies for reducing HE. The aryl hydrocarbon receptor (AHR) has been shown to participate in hyperglycemia-induced blood-brain barrier (BBB) dysfunction and brain injury after stroke. Herein, we investigated the role of AHR in hyperglycemia-induced HE in a male mouse model of ICH. Methods and Results CD1 mice (n=387) were used in this study. Mice were subjected to ICH by collagenase injection. Fifty percent dextrose was injected intraperitoneally 3 hours after ICH. AHR knockout clustered regularly interspaced short palindromic repeat was administered intracerebroventricularly to evaluate the role of AHR after ICH. A selective AHR inhibitor, 6,2',4'-trimethoxyflavone, was administered intraperitoneally 2 hours or 6 hours after ICH for outcome study. To evaluate the effect of AHR on HE, 3-methylcholanthrene, an AHR agonist, was injected intraperitoneally 2 hours after ICH. The results showed hyperglycemic ICH upregulated AHR accompanied by greater HE. AHR inhibition provided neurological benefits by restricting HE and preserving BBB function after hyperglycemic ICH. In vivo knockdown of AHR further limited HE and enhanced the BBB integrity. Hyperglycemia directly activated AHR as a physiological stimulus in vivo. The thrombospondin-1/transforming growth factor-ß/vascular endothelial growth factor axis partly participated in AHR signaling after ICH, which inhibited the expressions of BBB-related proteins, ZO-1 and Claudin-5. Conclusions AHR may serve as a potential therapeutic target to attenuate hyperglycemia-induced hematoma expansion and to preserve the BBB in patients with ICH.

Investigation on the Mental Health Status of ICU Practitioners and Analysis of Influencing Factors During the Stable Stage of COVID-19 Epidemic in China.

Objective: To understand the impact of COVID-19 epidemic on the mental health status of intensive care unit (ICU) practitioners in China, and to explore the relevant factors that may affect the mental health status of front-line medical workers so as to adopt efficient and comprehensive measures in a timely manner to protect the mental health of medical staff. Methods: The study covered most of the provinces in China, and a questionnaire survey was conducted based on the WeChat platform and the Wenjuanxing online survey tool. With the method of anonymous investigation, we chose ICU practitioners to participate in the investigation from April 5, 2020 to April 7, 2020. The respondents were divided into two groups according to strict criteria of inclusion and exclusion, those who participated in the rescue work of COVID-19 (COVID-19 group) and those who did not (non-COVID-19 group). The SCL-90 self-evaluation scale was used for the evaluation of mental health status of the subjects. Results: A total of 3,851 respondents completed the questionnaire. First, the overall mental health status of the targeted population, compared with the Chinese norm (n = 1,388), was reflected in nine related factor groups of the SCL-90 scale, and significant differences were found in every factor in both men and women, except for the interpersonal sensitivity in men. Second, the overall mental health of the non-COVID-19 group was worse than that of the COVID-19 group by the SCL-90 scale (OR = 1.98, 95% CI, 1.682-2.331). Third, we have revealed several influencing factors for their mental health in the COVID-19 group, current working status (P < 0.001), satisfaction of diet and accommodation (P < 0.05), occupational exposure (P = 0.005), views on the risk of infection (P = 0.034), and support of training (P = 0.01). Conclusion: The mental health status of the ICU practitioners in the COVID-19 group is better than that of the non-COVID-19 group, which could be attributed to a strengthened mentality and awareness of risks related to occupational exposure and enforced education on preventive measures for infectious diseases, before being on duty.

Pituitary adenylate cyclase-activating polypeptide attenuates mitochondria-mediated oxidative stress and neuronal apoptosis after subarachnoid hemorrhage in rats.

Mitochondria-mediated oxidative stress and neuronal apoptosis play an important role in early brain injury following subarachnoid hemorrhage (SAH). Pituitary adenylate cyclase-activating polypeptide (PACAP) has been shown to reduce oxidative stress and cellular apoptosis by maintaining mitochondrial function under stress. The objective of this study is to investigate the effects of PACAP on mitochondria dysfunction - induced oxidative stress and neuronal apoptosis in both vivo and vitro models of SAH. PACAP Knockout CRISPR and exogenous PACAP38 were used to verify the neuroprotective effects of PACAP in rats after endovascular perforation - induced SAH as well as in primary neuron culture after hemoglobin stimulation. The results showed that endogenous PACAP knockout aggravated mitochondria dysfunction - mediated ATP reduction, reactive oxygen species accumulation and neuronal apoptosis in ipsilateral hemisphere at 24 h after SAH in rats. The exogenous PACAP38 treatment provided both short- and long-term neurological benefits by attenuating mitochondria - mediated oxidative stress and neuronal apoptosis after SAH in rats. Consistently, the exogenous PACAP38 treatment presented similar neuroprotection in the primary neuron culture after hemoglobin stimulation. Pharmacological inhibition of adenylyl cyclase (AC) or extracellular signal-regulated kinase (ERK) partly abolished the anti-oxidative stress and anti-apoptotic effects provided by PACAP38 treatment after the experimental SAH both in vivo and in vitro, suggesting the involvement of the AC-cyclic adenosine monophosphate (cAMP)-protein kinase A (PKA) and ERK pathway. Collectively, PACAP38 may serve as a promising treatment strategy for alleviating early brain injury after SAH.

Kisspeptin-54 attenuates oxidative stress and neuronal apoptosis in early brain injury after subarachnoid hemorrhage in rats via GPR54/ARRB2/AKT/GSK3ß signaling pathway.

Oxidative stress-induced neuron apoptosis plays a crucial role in the early brain injury (EBI) after subarachnoid hemorrhage (SAH). Kisspeptin has been reported as antioxidant to reduce oxidative stress-induced neuronal cell death through G protein-coupled receptor 54 (GPR54). The goal of this study was to determine the neuroprotection of the Kisspeptin/GRP54 signaling pathway against EBI after SAH. Two hundred and ninety-two Sprague Dawley male rats were used and SAH was induced by the endovascular perforation. Exogenous Kisspeptin 54 (KP54) was delivered intranasally. Small interfering ribonucleic acid (siRNA) for endogenous KISS1, a selective GPR54 antagonist kisspeptin 234, or ß-arrestin 2 siRNA for ARRB2 (a functional adaptor of GPR54) were administered intracerebroventricularly. Post-SAH evaluations included neurobehavioral tests, SAH grade, Western blot, immunofluorescence, Fluoro-Jade C, TUNEL, and Nissl staining. The results showed that endogenous KISS1 knockdown aggravated but exogenous KP54 (1.0 nmol/kg) treatment attenuated neurological deficits, brain oxidative stress, and neuronal apoptosis at 24 h after SAH. The benefits of KP54 persisted to 28 days after SAH, which significantly improved cognitive function in SAH rats. The GPR54 blockade or the ARRB2 knockout offset the neuroprotective effects of KP54 in SAH rats. In conclusion, our results suggested that administration of KP54 attenuated oxidative stress, neuronal apoptosis and neurobehavioral impairments through GPR54/ARRB2/AKT/GSK3ß signaling pathway after SAH in rat. Thus, KP54 may provide an effective treatment strategy for SAH patients.

TREM (Triggering Receptor Expressed on Myeloid Cells)-1 Inhibition Attenuates Neuroinflammation via PKC (Protein Kinase C) δ/CARD9 (Caspase Recruitment Domain Family Member 9) Signaling Pathway After Intracerebral Hemorrhage in Mice.

Background and Purpose: Intracerebral hemorrhage (ICH) is a devastating subtype of stroke with high mortality and disability. Inflammatory response promotes secondary brain injury after ICH. TREM (triggering receptor expressed on myeloid cells)-1 is a key regulator of inflammation. The aim of this study was to evaluate the role of TREM-1 in neuroinflammatory response after ICH in mice. Methods: CD1 mice (n=275) were used in this study. Mice were subjected to ICH by autologous blood injection. TREM-1 knockout CRISPR was administered intracerebroventricularly to evaluate the role of TREM-1 after ICH. A selective TREM-1 inhibitor, LP17, was administered intranasally 2 hours after ICH. To elucidate TREM-1 signaling pathway, CARD9 (caspase recruitment domain family member 9) activation CRISPR was administered with LP17 and TREM-1 activating anti-mouse TREM-1 monoclonal antibody (mAb) was administered with Rottlerin, a specific PKC (protein kinase C) δ inhibitor. Lastly, to evaluate the role of HMGB1 (high-mobility group box 1) in TREM-1 mediated microglia activation, glycyrrhizin, an inhibitor of HMBG1 was administered with TREM-1 activating mAb. Neurobehavioral test, brain water content, Western blot, immunofluorescence staining, and coimmunoprecipitation was performed. Results: TREM-1 knockout reduced ICH-induced neurobehavioral deficits and neuroinflammatory response. The temporal expression of HMGB1, TREM-1, PKC δ, and CARD9 increased after ICH. TREM-1 was expressed on microglia. Intranasal administration of LP17 significantly decreased brain edema and improved neurobehavioral outcomes at 24 and 72 hours after ICH. LP17 promoted M2 microglia polarization and reduced proinflammatory cytokines after ICH, which was reversed with CARD9 activation CRISPR. TREM-1 mAb increased neurobehavior deficits, proinflammatory cytokines, and reduced M2 microglia after ICH, which was reversed with Rottlerin. HMBG1 interaction with TREM-1 increased after ICH, and glycyrrhizin reduced neuroinflammation and promoted M2 microglia which was reversed with TREM-1 mAb. Conclusions: This study demonstrated that TREM-1 enhanced neuroinflammation by modulating microglia polarization after ICH, and this regulation was partly mediated via PKC δ/CARD9 signaling pathway and increased HMGB1 activation of TREM-1.

CircPTK2-miR-181c-5p-HMGB1: a new regulatory pathway for microglia activation and hippocampal neuronal apoptosis induced by sepsis.

BACKGROUND: Circular RNA hsa_circ_0008305 (circPTK2), miR-181c-5p and High mobility group box-1 (HMGB1) had a targeted regulatory relationship through bioinformatics analysis. This study explained the effects of these genes in microglia and sepsis mice. METHODS: Lipopolysaccharide (LPS) or Cecal Ligation and Puncture (CLP) was used to induce inflammation cell model or sepsis mouse model, as needed. Gene levels were measured by enzyme linked immunosorbent assay (ELISA), quantitative real-time PCR or Western blot, as required. Apoptosis was detected by TUNEL assay, and RNase R was used to test the stability of circPTK2. Targeting relationships between genes were analyzed using bioinformatics analysis and dual luciferase assay. Morris water maze test and mitochondrial membrane potential (MMP) detection were conducted to analyze the effects of genes on cognitive dysfunction of mice. RESULTS: Lipopolysaccharide induction triggered the release of pro-inflammatory cytokines, the upregulation of HMGB1 and circPTK2, and the downregulation of miR-181c-5p in microglia. Overexpression of HMGB1 enhanced the effect of LPS, while silencing HMGB1 partially counteracted the effect of LPS. Moreover, miR-181c-5p was a target of circPTK2 and bound to HMGB1. MiR-181c-5p mimic partially reversed the functions of LPS and HMGB1 overexpression, reduced the levels of TNF-α, IL-1ß, and HMGB1, and inhibited apoptosis. CircPTK2 knockdown had the same effect as miR-181c-5p up-regulation. In vivo, sicircPTK2 improved cognitive function, restored MMP level, inhibited apoptosis, reduced the levels of inflammatory factors and apoptotic factors, and increased the survival rate of CLP-induced mice. CONCLUSION: Our research reveals that circPTK2 regulates microglia activation and hippocampal neuronal apoptosis induced by sepsis via miR-181c-5p-HMGB1 signaling.

Deep venous drainage variant rate and degree may be higher in patients with perimesencephalic than in non-perimesencephalic angiogram-negative subarachnoid hemorrhage.

OBJECTIVES: The basal vein of Rosenthal (BVR) variant is a potential origin of bleeding in angiogram-negative subarachnoid hemorrhage (AN-SAH). We compared the rate and degree of BVR variants in patients with perimesencephalic AN-SAH (PAN-SAH) and non-perimesencephalic AN-SAH (NPAN-SAH). METHODS: We retrospectively reviewed the records of AN-SAH patients admitted to our hospital between 2013 and 2018. The associations between variables (baseline characteristics, clinical and radiological data, and outcome) with bleeding patterns and degree of BVR variants were analyzed. Additionally, potential predictors of positive findings on repeated digital-subtracted angiogram (DSA), rebleeding, delayed cerebral infarction (DCI), and poor outcome were further studied. RESULTS: A total of 273 patients with AN-SAH were included. The incidence rate and degree of BVR variants were significantly higher in PAN-SAH patients compared with those in NPAN-SAH patients (p < 0.001). Patients with normal bilateral BVRs are more likely to have a severe prognosis and diffused blood distribution (p < 0.05). We found an increased rate of positive findings on repeated DSA, DCI, rebleeding, and poor outcome at 3 months and 1 year after discharge (all p < 0.05) in patients with bilateral normal BVRs. Bilateral normal BVRs were considered a risk factor (predictor) of positive findings on repeated DSA, rebleeding, and poor outcome (all p < 0.05). CONCLUSIONS: PAN-SAH patients have a higher rate and degree of BVR variants compared with patients with NPAN-SAH. Those AN-SAH patients with bilateral normal BVRs are more likely to be of arterial origin and are at risk of suffering from rebleeding and a poor outcome. KEY POINTS: • Patients with PAN-SAH have a higher rate and degree of BVR variants compared with patients with NPAN-SAH, which suggested that AN-SAH patients with normal BVRs are more likely to originate from arterial bleeding. • AN-SAH patients with normal BVRs are more likely to have positive findings on repeated DSA examinations, as well as an increased incidence of rebleeding and poor outcome, which may assist and guide neurologists in selecting treatment.

Mental health status of Chinese physicians working in intensive care unit.

PURPOSE: Physicians working in intensive care unit (ICU) are prone to suffer from mental health problems, but there are still very limited data of mental health status of ICU physicians in China. Therefore, this study was to investigate their psychological status. MATERIALS AND METHODS: ICU physicians were contacted electronically and asked to complete the Symptom Check-list 90 (SCL-90) for Chinese from December 13 to December 14 in 2018. A total of 1749 valid questionnaires were collected. Fifteen potential relevant factors that could affect the mental health status of ICU physicians were also analyzed by multivariate logistic regression. RESULTS: The total mean score of SCL-90 for surveyed subjects was 175.49 ± 65.79. Near half of the respondents were identified with psychological symptoms. The pooled estimates of all the nine factors, including somatization, obsession-compulsion, interpersonal-sensitivity, depression, anxiety, hostility, phobic anxiety, and paranoid ideation among ICU physicians, were significantly higher than those in the general population (P < 0.001). Multivariate analysis revealed that education, title, working hours per week, frequency of night shift were risk factors for psychological symptoms. CONCLUSIONS: The situation of psychological health of ICU physicians in China is worrying, and it is urgent to take some effective measures to improve their mental health.

Pituitary Adenylate Cyclase-Activating Polypeptide: A Promising Neuroprotective Peptide in Stroke.

The search for viable, effective treatments for acute stroke continues to be a global priority due to the high mortality and morbidity. Current therapeutic treatments have limited effects, making the search for new treatments imperative. Pituitary adenylate cyclase-activating polypeptide (PACAP) is a well-established cytoprotective neuropeptide that participates in diverse neural physiological and pathological activities, such as neuronal proliferation, differentiation, and migration, as well as neuroprotection. It is considered a promising treatment in numerous neurological diseases. Thus, PACAP bears potential as a new therapeutic strategy for stroke treatment. Herein, we provide an overview pertaining to the current knowledge of PACAP, its receptors, and its potential neuroprotective role in the setting of stroke, as well as various mechanisms of neuroprotection involving ionic homeostasis, excitotoxicity, cell edema, oxidative stress, inflammation, and cell death, as well as the route of PACAP administration.

Pituitary Adenylate Cyclase-Activating Polypeptide Attenuates Brain Edema by Protecting Blood-Brain Barrier and Glymphatic System After Subarachnoid Hemorrhage in Rats.

Brain edema is a vital contributor to early brain injury after subarachnoid hemorrhage (SAH), which is responsible for prolonged hospitalization and poor outcomes. Pharmacological therapeutic targets on edema formation have been the focus of research for decades. Pituitary adenylate cyclase-activating polypeptide (PACAP) has been shown to participate in neural development and brain injury. Here, we used PACAP knockout CRISPR to demonstrate that endogenous PACAP plays an endogenous neuroprotective role against brain edema formation after SAH in rats. The exogenous PACAP treatment provided both short- and long-term neurological benefits by preserving the function of the blood-brain barrier and glymphatic system after SAH. Pretreatment of inhibitors of PACAP receptors showed that the PACAP-involved anti-edema effect and neuroprotection after SAH was facilitated by the selective PACAP receptor (PAC1). Further administration of adenylyl cyclase (AC) inhibitor and sulfonylurea receptor 1 (SUR1) CRISPR activator suggested that the AC-cyclic adenosine monophosphate (cAMP)-protein kinase A (PKA) axis participated in PACAP signaling after SAH, which inhibited the expression of edema-related proteins, SUR1 and aquaporin-4 (AQP4), through SUR1 phosphorylation. Thus, PACAP may serve as a potential clinical treatment to alleviate brain edema in patients with SAH.

Minocycline Attenuates Experimental Subarachnoid Hemorrhage in Rats.

BACKGROUD: The aim of this study was to evaluate the therapeutic effect of minocycline on treating experimental subarachnoid hemorrhage (SAH) in rats and to explore its possible molecular mechanism. METHODS: SAH was induced in male Sprague-Dawley rats by endovascular perforation. The rats were treated with minocycline (25 mg/kg or 50 mg/kg) or saline at 2 hand 12 h post SAH. Neurological function, cerebral hemorrhage, and edema were scored at 48 h post SAH. Cell death and P2X4 receptor (P2X4R) expression were observed in the prefrontal cortex (PFC). RESULTS: Treatment with a highdose of minocycline significantly improved the neurological function score, and attenuated cerebral hemorrhage and edema. Low-dose minocycline could reduce hemorrhage, but the effect on neurological deficits and brain edema was not obvious. Minocycline treatment could alleviate neuronal apoptosis in the PFC, which was related to reduced expression of inflammatory cytokines. Immunofluorescence showed that P2X4R on microglia was activated after SAH. Minocycline treatment inhibited P2X4R activation and further suppressed the phosphorylation of downstream p38 MAPK. CONCLUSIONS: Minocycline plays a neuroprotective role by attenuating early brain injury after experimental SAH. The therapeutic mechanism of minocycline may be mediated by the inhibition of P2X4R on microglia.

Early post-haemorrhagic stroke testosterone and oestradiol levels and long-term risk of death.

OBJECTIVE: The influence of oestrogen and testosterone replacement on stroke risk has been examined, as well as mechanisms by which oestrogen may protect from post-stroke damage. However, whether testosterone levels in the early time period after haemorrhagic stroke influence long-term mortality has not previously been investigated. We examined whether these concentrations were predictive of risk of death. SETTING: University hospital. DESIGN: Prospective study. MAIN MEASURES: Testosterone and oestrogen levels in the week after haemorrhagic stroke were measured, and the predictive value of these levels and other clinical parameters such as the size, location and severity of the stroke on mortality during the three-year length of the study were assessed. RESULTS: Glasgow Coma Scale and low testosterone/oestradiol ratio on post-stroke day 7 were independent predictors of mortality. Stroke location and hematoma volume had no predictive power. CONCLUSION: The testosterone/oestradiol ratio on day 7 after a haemorrhagic stroke is an independent predictor of mortality during later months.