The relationship between the extent of posterior limb of the internal capsule damage measured by non-contrast computed tomography and clinical outcomes after basal ganglia hemorrhage.

Assessing the extent of damage to the posterior limb of the internal capsule (PLIC) is important for early prediction of clinical outcomes in intracerebral hemorrhage (ICH) patients. Currently, using MRI to reconstruct the extent of damage to PLIC is not suitable for quick assessment of prognosis in emergency settings. We aimed to investigate whether the PLIC damage quantified by non-contrast computed tomography (NCCT) is associated with clinical outcomes after basal ganglia intracerebral hemorrhage (BG-ICH). This study retrospectively included 146 BG-ICH patients from the Department of Neurosurgery at the Second Affiliated Hospital of Chongqing Medical University. The damage to the PLIC was quantified using Tangency X measured by NCCT. The importance of features is determined using the Boruta algorithm and Least Absolute Shrinkage and Selection Operator (LASSO) regression. Multivariate logistic regression models were established to examine the impact of PLIC damage on outcomes. Restricted Cubic Splines (RCS) were used to explore potential nonlinear relationships, and Receiver Operating Characteristic (ROC) curves were used to compare the predictive performance of Tangency X with other scoring systems for 6-month neurological outcomes (poor outcomes [mRS: 3-6]). In the multivariate logistic regression adjusting for all covariates, Tangency X was independently associated with an increased risk of poor outcomes (OR = 1.32, 95% CI: 1.17-1.52) in BG-ICH patients. There is a nonlinear relationship between Tangency X and poor outcomes. Specifically, the risk of poor outcomes increases by 1.29 times (OR = 1.29, 95% CI: 1.09-1.67) for each additional 1 mm increase in Tangency X beyond 4 mm. We next observed that the AUC for Tangency X in predicting poor outcomes is 0.8511. The extent of PLIC damage measured by NCCT may represent a promising predictor of poor outcomes after BG-ICH.

Inhibition of acid-sensing receptor GPR4 attenuates neuronal ferroptosis via RhoA/YAP signaling in a rat model of subarachnoid hemorrhage.

BACKGROUND AND PURPOSE: Subarachnoid hemorrhage (SAH) is a devastating stroke, in which acidosis is one of detrimental complications. The extracellular pH reduction can activate G protein-coupled receptor 4 (GPR4) in the brain. Yet, the extent to which proton-activated GPR4 contributes to the early brain injury (EBI) post-SAH remains largely unexplored. Ferroptosis, iron-dependent programmed cell death, has recently been shown to contribute to EBI. We aimed to investigate the effects of GPR4 inhibition on neurological deficits and neuronal ferroptosis after SAH in rats. METHODS: A total 253 Sprague Dawley (SD) male rats (weighing 275-330g) were utilized in this study. SAH was induced by endovascular perforation. NE-52-QQ57 (NE), a selective antagonist of GPR4 was administered intraperitoneally 1-h post-SAH. To explore the mechanisms, RhoA activator U-46619 and YAP activator PY-60 were delivered intracerebroventricularly. Short- and long-term neurobehavior, SAH grading, Western blot assay, ELISA assay, immunofluorescence staining, and transmission electron microscopy was performed post-SAH. RESULTS: Following SAH, there was an upregulation of GPR4 expression in neurons. GPR4 inhibition by NE improved both short-term and long-term neurological outcomes post-SAH. NE also reduced neuronal ferroptosis, as evidenced by decreased lipid peroxidation products 4HNE and MDA levels in brain tissues, and reduced mitochondrial shrinkage, increased mitochondria crista and decreased membrane density. The application of either U-46619 or PY-60 partially offset the neuroprotective effects of NE on neuronal ferroptosis in SAH rats. CONCLUSIONS: This study demonstrated that acid-sensing receptor GPR4 contributed to neuronal ferroptosis after SAH via RhoA/YAP pathway, and NE may be a potential therapeutic strategy to attenuate GPR4 mediated neuronal ferroptosis and EBI after SAH.

Mitochondrial ferritin upregulation by deferiprone reduced neuronal ferroptosis and improved neurological deficits via NDRG1/Yap pathway in a neonatal rat model of germinal matrix hemorrhage.

Ferroptosis contributes to brain injury after germinal matrix hemorrhage (GMH). Mitochondrial ferritin (FTMT), a novel mitochondrial outer membrane protein, reduces oxidative stress in neurodegenerative diseases. In vitro, Deferiprone has been shown to upregulate FTMT. However, the effects of FTMT upregulation by Deferiprone on neuronal ferroptosis after GMH and its underlying mechanism has not been investigated. In our study, 389 Sprague-Dawley rat pups of postnatal day 7 were used to establish a collagenase-induced GMH model and an iron-overload model of intracerebral FeCl2 injection. The brain expressions of FTMT, N-myc downstream-regulated gene-1 (NDGR1), Yes-associated protein (YAP), ferroptosis-related molecules including transferrin receptor (TFR) and acyl-CoA synthase long-chain family member 4 (ACSL4) were increased after GMH. FTMT agonist Deferiprone improved neurological deficits and hydrocephalus after GMH. Deferiprone or Adenovirus-FTMT enhanced YAP phosphorylation at the Ser127 site and attenuated ferroptosis, which was reversed by NDRG1 CRISPR Knockout. Iron overload induced neuronal ferroptosis and neurological deficits, which were improved by YAP CRISPR Knockout. Collectively, FTMT upregulation by Deferiprone reduced neuronal ferroptosis and neurological deficits via the NDRG1/YAP signaling pathway after GMH. Deferiprone may serve as a potential non-invasive treatment for GMH patients.

Beyond the Gut: The intratumoral microbiome's influence on tumorigenesis and treatment response.

The intratumoral microbiome (TM) refers to the microorganisms in the tumor tissues, including bacteria, fungi, viruses, and so on, and is distinct from the gut microbiome and circulating microbiota. TM is strongly associated with tumorigenesis, progression, metastasis, and response to therapy. This paper highlights the current status of TM. Tract sources, adjacent normal tissue, circulatory system, and concomitant tumor co-metastasis are the main origin of TM. The advanced techniques in TM analysis are comprehensively summarized. Besides, TM is involved in tumor progression through several mechanisms, including DNA damage, activation of oncogenic signaling pathways (phosphoinositide 3-kinase [PI3K], signal transducer and activator of transcription [STAT], WNT/ß-catenin, and extracellular regulated protein kinases [ERK]), influence of cytokines and induce inflammatory responses, and interaction with the tumor microenvironment (anti-tumor immunity, pro-tumor immunity, and microbial-derived metabolites). Moreover, promising directions of TM in tumor therapy include immunotherapy, chemotherapy, radiotherapy, the application of probiotics/prebiotics/synbiotics, fecal microbiome transplantation, engineered microbiota, phage therapy, and oncolytic virus therapy. The inherent challenges of clinical application are also summarized. This review provides a comprehensive landscape for analyzing TM, especially the TM-related mechanisms and TM-based treatment in cancer.

PEDF-34 attenuates neurological deficit and suppresses astrocyte-dependent neuroinflammation by modulating astrocyte polarization via 67LR/JNK/STAT1 signaling pathway after subarachnoid hemorrhage in rats.

BACKGROUND: Reactive astrocytes participate in various pathophysiology after subarachnoid hemorrhage (SAH), including neuroinflammation, glymphatic-lymphatic system dysfunction, brain edema, BBB disruption, and cell death. Astrocytes transform into two new reactive phenotypes with changed morphology, altered gene expression, and secretion profiles, termed detrimental A1 and beneficial A2. This study investigates the effect of 67LR activation by PEDF-34, a PEDF peptide, on neuroinflammation and astrocyte polarization after the experimental SAH. METHODS: A total of 318 male adult Sprague-Dawley rats were used in experiments in vivo, of which 272 rats were subjected to the endovascular perforation model of SAH and 46 rats underwent sham surgery. 67LR agonist (PEDF-34) was administrated intranasally 1 h after SAH. 67LR-specific inhibitor (NSC-47924) and STAT1 transcriptional activator (2-NP) were injected intracerebroventricularly 48 h before SAH. Short- and long-term neurological tests, brain water content, immunostaining, Nissl staining, western blot, and ELISA assay were performed. In experiments in vitro, primary astrocyte culture with hemoglobin (Hb) stimulation was used to mimic SAH. The expression of the PEDF-34/67LR signaling pathway and neuro-inflammatory cytokines were assessed using Western blot, ELISA, and immunohistochemistry assays both in vivo and in vitro. RESULTS: Endogenous PEDF and 67LR expressions were significantly reduced at 6 h after SAH. 67LR was expressed in astrocytes and neurons. Intranasal administration of PEDF-34 significantly reduced brain water content, pro-inflammatory cytokines, and short-term and long-term neurological deficits after SAH. The ratio of p-JNK/JNK and p-STAT1/STAT1 and the expression of CFB and C3 (A1 astrocytes marker), significantly decreased after PEDF-34 treatment, along with fewer expression of TNF-α and IL-1ß at 24 h after SAH. However, 2-NP (STAT1 transcriptional activator) and NSC-47924 (67LR inhibitor) reversed the protective effects of PEDF-34 in vivo and in vitro by promoting A1 astrocyte polarization with increased inflammatory cytokines. CONCLUSION: PEDF-34 activated 67LR, attenuating neuroinflammation and inhibiting astrocyte A1 polarization partly via the JNK/STAT1 pathway, suggesting that PEDF-34 might be a potential treatment for SAH patients.

Mitochondrial ferritin upregulation reduced oxidative stress and blood-brain-barrier disruption by maintaining cellular iron homeostasis in a neonatal rat model of germinal matrix hemorrhage.

Germinal matrix hemorrhage (GMH) is a devasting neurological disease in premature newborns. After GMH, brain iron overload associated with hemoglobin degradation contributed to oxidative stress, causing disruption of the already vulnerable blood-brain barrier (BBB). Mitochondrial ferritin (FTMT), a novel mitochondrial outer membrane protein, is crucial in maintaining cellular iron homeostasis. We aimed to investigate the effect of FTMT upregulation on oxidative stress and BBB disruption associated with brain iron overload in rats. A total of 222 Sprague-Dawley neonatal rat pups (7 days old) were used to establish a collagenase-induced GMH model and an iron-overload model of intracerebral FeCl2 injection. Deferiprone was administered via gastric lavage 1 h after GMH and given daily until euthanasia. FTMT CRISPR Knockout and adenovirus (Ad)-FTMT were administered intracerebroventricularly 48 h before GMH and FeCl2 injection, respectively. Neurobehavioral tests, immunofluorescence, Western blot, Malondialdehyde measurement, and brain water content were performed to evaluate neurobehavior deficits, oxidative stress, and BBB disruption, respectively. The results demonstrated that brain expressions of iron exporter Ferroportin (FPN) and antioxidant glutathione peroxidase 4 (GPX4) as well as BBB tight junction proteins including Claudin-5 and Zona Occulta (ZO)-1 were found to be decreased at 72 h after GMH. FTMT agonist Deferiprone attenuated oxidative stress and preserved BBB tight junction proteins after GMH. These effects were partially reversed by FTMT CRISPR Knockout. Iron overload by FeCl2 injection resulted in oxidative stress and BBB disruption, which were improved by Ad-FTMT mediated FTMT overexpression. Collectively, FTMT upregulation is neuroprotective against brain injury associated with iron overload. Deferiprone reduced oxidative stress and BBB disruption by maintaining cellular iron homeostasis partially by the upregulating of FTMT after GMH. Deferiprone may be an effective treatment for patients with GMH.

Fractalkine Enhances Hematoma Resolution and Improves Neurological Function via CX3CR1/AMPK/PPARγ Pathway After GMH.

BACKGROUND: Hematoma clearance has been a proposed therapeutic strategy for hemorrhagic stroke. This study investigated the impact of CX3CR1 (CX3C chemokine receptor 1) activation mediated by r-FKN (recombinant fractalkine) on hematoma resolution, neuroinflammation, and the underlying mechanisms involving AMPK (AMP-activated protein kinase)/PPARγ (peroxisome proliferator-activated receptor gamma) pathway after experimental germinal matrix hemorrhage (GMH). METHODS: A total of 313 postnatal day 7 Sprague Dawley rat pups were used. GMH was induced using bacterial collagenase by a stereotactically guided infusion. r-FKN was administered intranasally at 1, 25, and 49 hours after GMH for short-term neurological evaluation. Long-term neurobehavioral tests (water maze, rotarod, and foot-fault test) were performed 24 to 28 days after GMH with the treatment of r-FKN once daily for 7 days. To elucidate the underlying mechanism, CX3CR1 CRISPR, or selective CX3CR1 inhibitor AZD8797, was administered intracerebroventricularly 24 hours preinduction of GMH. Selective inhibition of AMPK/PPARγ signaling in microglia via intracerebroventricularly delivery of liposome-encapsulated specific AMPK (Lipo-Dorsomorphin), PPARγ (Lipo-GW9662) inhibitor. Western blot, Immunofluorescence staining, Nissl staining, Hemoglobin assay, and ELISA assay were performed. RESULTS: The brain expression of FKN and CX3CR1 were elevated after GMH. FKN was expressed on both neurons and microglia, whereas CX3CR1 was mainly expressed on microglia after GMH. Intranasal administration of r-FKN improved the short- and long-term neurobehavioral deficits and promoted M2 microglia polarization, thereby attenuating neuroinflammation and enhancing hematoma clearance, which was accompanied by an increased ratio of p-AMPK (phosphorylation of AMPK)/AMPK, Nrf2 (nuclear factor erythroid 2-related factor 2), PPARγ, CD36 (cluster of differentiation 36), CD163 (hemoglobin scavenger receptor), CD206 (the mannose receptor), and IL (interleukin)-10 expression, and decreased CD68 (cluster of differentiation 68), IL-1ß, and TNF (tumor necrosis factor) α expression. The administration of CX3CR1 CRISPR or CX3CR1 inhibitor (AZD8797) abolished the protective effect of FKN. Furthermore, selective inhibition of microglial AMPK/PPARγ signaling abrogated the anti-inflammation effects of r-FKN after GMH. CONCLUSIONS: CX3CR1 activation by r-FKN promoted hematoma resolution, attenuated neuroinflammation, and neurological deficits partially through the AMPK/PPARγ signaling pathway, which promoted M1/M2 microglial polarization. Activating CX3CR1 by r-FKN may provide a promising therapeutic approach for treating patients with GMH.

Controlling nutritional status score and prognostic nutrition index predict the outcome after severe traumatic brain injury.

OBJECTIVES: Immune-nutritional status is correlated with a clinical outcome in critical illness. Recently, controlling nutritional status (CONUT) score and prognostic nutrition index (PNI) has been reported to predict prognosis following cancer and other diseases. The aim of this study was to explore the relationship between the CONUT score and PNI and 6-month outcome in patients with severe traumatic brain injury (STBI). METHODS: We retrospectively analyzed the clinical data of 78 patients with STBI, including the CONUT score and PNI. Patients were divided into high CONUT group and low CONUT group. Patients were also divided into high PNI and low PNI group respectively. The 6-month outcome was evaluated by the modified Rankin scale (mRS). The unfavorable outcome was defined as mRS score ≥3. RESULTS: The unfavorable outcome group had lower Glasgow coma scale (GCS) scores, serum albumin, total cholesterol, PNI, and higher CONUT scores (P < 0.05). Both CONUT scores and PNI were strongly correlated with mRS (r = 0.429, P < 0.05; r = -0.590, P < 0.05, respectively). After adjustment for confounding factors, the odds ratios of CONUT scores and PNI for predicting unfavorable outcome were 10.478 (95% CI: 2.793-39.301) and -0.039 (95% CI: 0.008-0.204), respectively. The area under the curve (AUC) of CONUT scores for predicting unfavorable outcome was 0.777 (95% CI: 0.674-0.880, P < 0.01), which was similar to PNI (0.764, 95% CI: 0.657-0.87, P < 0.01). CONCLUSION: Both CONUT scores and PNI might be novel independent predictors of the poor outcome in STBI.

Systemic immune-inflammation index predicts the outcome after aneurysmal subarachnoid hemorrhage.

Systemic inflammatory response is closely related to the pathogenesis and prognosis in critical patients. Recently, systemic immune-inflammation index (SII), an indicator of systemic inflammatory response, was proved to predict the outcome in cancerous and non-cancerous diseases. The aim of this study is to investigate the association between SII on admission and 6-month outcome in patients with aneurysmal subarachnoid hemorrhage (aSAH). The clinical data and prognosis of 76 patients with aSAH were analyzed. The 6-month outcome was assessed by the modified Rankin scale(mRS). The unfavorable outcome was defined as mRS score ≥ 3. In addition, multivariate analysis was conducted to investigate factors independently associated with the favorable outcome. Receiver operating characteristic (ROC) curve analysis was undertaken to identify the best cut-off value of SII for the discriminate between favorable and unfavorable outcome in these patients. Thirty-six patients (47.4%) in our study had an unfavorable outcome (mRS ≥ 3) at 6 months, and twenty-four (66.7%) of them were in the high-SII group. A significantly higher SII on admission was observed in patients with unfavorable functional outcome at 6 months. Binary logistic regression analysis showed that there was an independent association between SII on admission and 6-month clinical outcome (adjusted OR = 4.499, 95%CI: 1.242-16.295, P < 0.05). The AUC of the SII for predicting unfavorable outcome was 0.692 (95% CI: 0.571-0.814, P < 0.05). Systemic immune-inflammation index (SII) could be a novel independent prognostic factor for aSAH patients at the early stage of the disease.

Prediction of Hematoma Expansion in Patients With Intracerebral Hemorrhage Using Thromboelastography With Platelet Mapping: A Prospective Observational Study.

Background and Purpose: The purpose of the study was to evaluate the usefulness of thromboelastography with platelet mapping (TEG-PM) for predicting hematoma expansion (HE) and poor functional outcome in patients with intracerebral hemorrhage (ICH). Methods: Patients with primary ICH who underwent baseline computed tomography (CT) and TEG-PM within 6 h after symptom onset were enrolled in the observational cohort study. We performed univariate and multivariate logistic regression models to assess the association of admission platelet function with HE and functional outcome. In addition, a receiver operating characteristic (ROC) curve analysis investigated the accuracy of platelet function in predicting HE. A mediation analysis was undertaken to determine causal associations among platelet function, HE, and outcome. Results: Of 142 patients, 37 (26.1%) suffered HE. Multivariate logistic regression identified arachidonic acid (AA) and adenosine diphosphate (ADP) inhibition as significant independent predictors of HE. The area under the ROC curves was 0.727 for AA inhibition and 0.721 for ADP inhibition. Optimal threshold for AA inhibition was 41.75% (75.7% sensitivity; 67.6% specificity) and ADP inhibition was 65.8% (73.0% sensitivity; 66.7% specificity). AA and ADP inhibition were also associated with worse 3-month outcomes after adjusting for age, admission Glasgow Coma Scale score, intraventricular hemorrhage, baseline hematoma volume, and hemoglobin. The mediation analysis showed that the effect of higher platelet inhibition with poor outcomes was mediated through HE. Conclusions: These findings suggest that the reduced platelet response to ADP and AA independently predict HE and poor outcome in patients with ICH. Platelet function may represent a modifiable target of ICH treatment.

Gint4.T-Modified DNA Tetrahedrons Loaded with Doxorubicin Inhibits Glioma Cell Proliferation by Targeting PDGFRß.

Glioma is one of the deadliest intrinsic brain tumours due to its invasive growth. The effect of glioma treatment is poor because of the presence of the blood-brain barrier and blood tumour barrier and insufficient drug targeting. DNA tetrahedrons (TDN) show great potential for drug delivery and may be a novel therapeutic strategy for glioma. In this study, we used TDN to deliver doxorubicin (DOX) for the glioma therapy. Gint4.T, an aptamer that could recognize platelet-derived growth factor receptor ß on tumour cell, was used to modify TDN (Apt-TDN) for targeted drug delivery. The TDN were self-assembled by one-step synthesis, which showed small size (10 nm) and negative charge. Fetal bovine serum test showed its stability as a drug delivery vehicle. Apt-TDN could be effectively taken up by U87MG cells. Compared with DOX and DOX@TDN (TDN loaded with DOX), the DOX@Apt-TDN (Gint4.T-modified TDN loaded with DOX) showed more early apoptosis rate, higher cell cycle arrest, and greater cytotoxicity towards U87MG cells. In conclusion, our findings indicated that DOX@Apt-TDN provides a novel therapy with promising clinical application for gliomas patients.

Blood Type O Predicts Hematoma Expansion in Patients with Intracerebral Hemorrhage.

BACKGROUND: Hematoma expansion after acute spontaneous intracerebral hemorrhage (ICH) is well established to result in poor prognosis. Recent studies have demonstrated that the ABO blood type system has potential implications on hemostatic properties. The purpose of this study was to explore the potential association of blood type O with hematoma expansion in patients with ICH and validate the usefulness in predicting early hematoma expansion. METHODS: We retrospectively enrolled consecutive patients with ICH who underwent baseline computed tomographic (CT) scan within 6 hours after onset of symptoms. The follow-up CT scan was available within 48 hours after the baseline CT scan. Hematoma expansion was defined as total volume increase more than 33% or more than 6 mL. We performed univariate and multivariate logistic regression analyses to investigate the relationship between the different types of blood (type O versus other types) and hematoma expansion. RESULTS: A total of 210 patients were included in the study. Among them, 72 patients (34.3%) carried blood type O. Hematoma expansion was more common in patients with blood type O (41.7%) than those with other blood types (18.1%; P < .001). Furthermore, the time to baseline CT scan, blood type O, and admission Glasgow Coma Scale score were demonstrated to be independent predictors of hematoma expansion in multivariate logistic regression analysis model. The sensitivity, specificity, positive, and negative predictive values of blood type O for predicting hematoma expansion were 54.5%, 72.9%, 41.6%, and 81.9%, respectively. CONCLUSIONS: Our findings suggest that blood type O represents an independent predictor of hematoma expansion after ICH. Hemostasis seems to be involved in expansion and may represent an important treatment target.

The association of neutrophil-to-lymphocyte ratio and delayed cerebral ischemia in patients with aneurysmal subarachnoid hemorrhage: possible involvement of cerebral blood perfusion.

Background and purpose: Emerging evidence suggests that systemic inflammation is associated with the pathophysiological process of delayed cerebral ischemia (DCI) after aneurysmal subarachnoid hemorrhage (aSAH). This study aimed to investigate the association of white blood cell (WBC) count and neutrophil-to-lymphocyte ratio (NLR) with the occurrence of DCI in SAH patients. Methods: A total of 122 patients diagnosed with aSAH within 72 h of onset were retrospectively enrolled. The count of WBC, neutrophil count (NC), and lymphocyte (LC) was collected on admission. Computed tomography perfusion was performed within 7 days after SAH. The occurrence of DCI was recorded during the hospitalization. Results: Among enrolled patients, 43 (35.2%) developed DCI during hospitalization. Patients who developed DCI had a higher count of WBC, NC, and NLR as well as a lower count of LC. NC and NLR were independently associated with the occurrence of DCI, while NLR was the best predictive parameter according to the receiver operating characteristic curve. Moreover, there was a strong correlation between NLR and mean cerebral blood flow, mean transit time and mean time to peak. Conclusion: Leukocytosis is an early pathology of SAH, and NLR may be a practical predictor for the occurrence of DCI in SAH patients.

Improvement of Deep Brain Stimulation in Dyskinesia in Parkinson's Disease: A Meta-Analysis.

Background: Deep brain stimulation (DBS) of the subthalamic nucleus (STN) or globus pallidus internus (GPi) have been proven to be equally effective in improving motor-symptoms for advanced Parkinson's disease (PD) patients. However, it is unclear that which target stimulation is more effective in reducing dyskinesia. We conducted the meta-analysis to evaluate the efficacy of STN and GPi-DBS in the dyskinesia. Methods: A systematic search was performed in PubMed, Embase, and the Cochrane Library databases. Controlled trials about the dyskinesia comparing the efficacy of GPi and STN DBS were included. Clinical data of dyskinesia and levodopa equivalent doses (LED) were collected for the meta-analysis. Results: Eight eligible trials containing a total of 822 patients were included in this meta-analysis. Our results showed that GPi DBS offered a greater reduction of dyskinesia than STN DBS at 12 months after surgery, with an overall pooled SMD of 0.32 (95% CI = 0.06 to 0.59, P = 0.02). Treatment of STN DBS was associated with a greater reduction of LED compared with GPi DBS, with a change score of -320.55 (95% CI = -401.36 to -239.73, P < 0.00001). Conclusion: GPi DBS is superior to reduce dyskinesia than STN DBS at 12 months after surgery for advanced PD patients. Further studies should focus on the different mechanism for dyskinesia reduction by GPi or STN DBS.

Thromboelastography with Platelet Mapping Detects Platelet Dysfunction in Patients with Aneurysmal Subarachnoid Hemorrhage with Rebleeding.

BACKGROUND: Aneurysmal subarachnoid hemorrhage (aSAH) has high rates of disability and mortality, and aneurysm rebleeding is associated with poor functional outcomes. Thrombelastography with platelet mapping (TEG-PM) measures platelet function; however, it has not yet been researched in aSAH. We aimed to use TEG-PM to detect changes in platelet function in patients with aSAH and the difference in patients with and without rebleeding. METHODS: We retrospectively included patients with aSAH who underwent a TEG-PM test on admission. Rebleeding was diagnosed according to clinical and imaging data. TEG-PM data of patients with unruptured intracranial aneurysms (UIA) were also obtained as controls. Univariate and multivariate logistic regression models were performed to investigate the relationship between the platelet function and rebleeding. RESULTS: A total of 245 aSAH patients and 32 UIA patients were included in our study. Compared with controls, patients with aSAH demonstrated higher arachidonic acid (AA) and adenosine diphosphate (ADP) inhibition of platelet function (P<0.05). Among them, 27 patients with Hunt-Hess grade IV or V were classified as the severe SAH group. There was a significant correlation between the severe SAH group and the degree of pathway inhibition (P<0.05). Furthermore, AA (Spearman's r=0.264, P<0.001) and ADP (Spearman's r=0.183, P=0.004) inhibition were elevated in Hunt-Hess grade-dependent manners. The AA (Spearman's r=0.169, P=0.008) and ADP (Spearman's r=0.233, P<0.001) inhibition were also significantly correlated with Fisher grade. Thirty-five patients (14.3%) suffered rebleeding. Rebleeding was significantly correlated with systolic blood pressure (P=0.011), diastolic blood pressure (P=0.008), Hunt-Hess grade (P=0.034), Fisher grade (P=0.015), AA inhibition (P<0.001), and ADP inhibition (P<0.001). Multivariate logistic regression analysis model revealed that both AA (P=0.037) and ADP inhibition (P=0.008) were independent determinants for rebleeding. CONCLUSION: TEG-PM may assess platelet dysfunction in patients with aSAH, and the diminished platelet response to ADP and AA may be associated with rebleeding. These findings deserve further investigation.