Clinical outcomes after microsurgical resection of giant lateral ventricular meningiomas.

Giant lateral ventricular meningiomas (LVMs), with the largest diameter of at least 5 cm, form a distinct subset. The incidence of giant LVMs is considered to be relatively low. Here, we evaluated clinical characteristics, and clinical outcomes after microsurgical resection, especially functional outcomes and morbidity of giant LVMs. We retrospectively reviewed 49 patients with LVMs, including 18 giant LVMs from 2012 to 2020. And we analyzed clinical, histopathological, surgical, and outcome data at our institution. Giant LVMs were most commonly present in the fourth decade of patients with the male-to-female ratio of 1:2. The most common subtypes were transitional and fibrous. Most lesions were resected via the temporal or parieto-occipital approach in our series. The median volume of blood loss was higher in the giant group (900 vs. 600 ml, p = 0.02). Meanwhile, the median length of hospital stay was prolonged for giant LVMs (20.5 vs. 16.0 days, p < 0.01). The proportion of discharged functional deterioration was higher in giant LVMs (38.9% vs. 6.5%, p = 0.02). However, there was no statistical significance between functional deterioration and tumor size at long-term follow-up (p = 0.28). Giant LVMs patients suffered from neurological and regional complications more commonly, particularly from a postoperative hematoma (4/18 vs. 1/31), and hydrocephalus (2/18 vs. 0/31). Patients with giant LVMs had a high incidence of immediate functional deterioration after microsurgery, and there was no difference in functional deterioration between the giant and non-giant LVMS during long-term follow-up. Microsurgery entails a higher complication rate in giant LVMs. We need to pay special attention to preventing postoperative hematoma and hydrocephalus.

The role of the astrocyte in subarachnoid hemorrhage and its therapeutic implications.

Subarachnoid hemorrhage (SAH) is an important public health concern with high morbidity and mortality worldwide. SAH induces cell death, blood-brain barrier (BBB) damage, brain edema and oxidative stress. As the most abundant cell type in the central nervous system, astrocytes play an essential role in brain damage and recovery following SAH. This review describes astrocyte activation and polarization after SAH. Astrocytes mediate BBB disruption, glymphatic-lymphatic system dysfunction, oxidative stress, and cell death after SAH. Furthermore, astrocytes engage in abundant crosstalk with other brain cells, such as endothelial cells, neurons, pericytes, microglia and monocytes, after SAH. In addition, astrocytes also exert protective functions in SAH. Finally, we summarize evidence regarding therapeutic approaches aimed at modulating astrocyte function following SAH, which could provide some new leads for future translational therapy to alleviate damage after SAH.

The Attenuation Value Within the Non-hypodense Region on Non-contrast Computed Tomography of Spontaneous Cerebral Hemorrhage: A Long-Neglected Predictor of Hematoma Expansion.

Background and Purpose: The ability of attenuation value of the non-hypodense region of hematoma in non-contrast computed tomography (NCCT) for predicting hematoma expansion (HE) remains unclear. Our purpose is to explore this relationship. Methods: Two cohorts of patients were collected for analysis. The region where we measured hematoma attenuation values was limited to the non-hypodense region that was not adjacent to the normal brain tissue on NCCT. The critical attenuation value was derived via receiver operating characteristic (ROC) curve analysis in the derivation cohort and its predictive ability was validated in the validation cohort. Independent relationships between predictors, such as critical attenuation value of the non-hypodense region and HE were analyzed using the least absolute shrinkage and selection operator (LASSO) regression and multivariate logistic analysis. Results: The results showed that the attenuation value <64 Hounsfield units (HU) was independently associated with HE [odds ratio (OR), 4.118; 95% confidential interval (CI), 1.897-9.129, p < 0.001] and the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), positive likelihood ratio (PLR), negative likelihood ratio (NLR), and area under the curve (AUC) for predicting HE were 36.11%, 81.71%, 1.97, 0.78, 44.8%, 75.7%, and 0.589, respectively. Conclusions: Our research explored and validated the relationship between the attenuation value of the non-hypodense region of hematoma and HE. The attenuation value < 64 HU was an appropriate indicator of early HE.

Mitochondrial Dynamics: A Potential Therapeutic Target for Ischemic Stroke.

Stroke is one of the leading causes of death and disability worldwide. Brain injury after ischemic stroke involves multiple pathophysiological mechanisms, such as oxidative stress, mitochondrial dysfunction, excitotoxicity, calcium overload, neuroinflammation, neuronal apoptosis, and blood-brain barrier (BBB) disruption. All of these factors are associated with dysfunctional energy metabolism after stroke. Mitochondria are organelles that provide adenosine triphosphate (ATP) to the cell through oxidative phosphorylation. Mitochondrial dynamics means that the mitochondria are constantly changing and that they maintain the normal physiological functions of the cell through continuous division and fusion. Mitochondrial dynamics are closely associated with various pathophysiological mechanisms of post-stroke brain injury. In this review, we will discuss the role of the molecular mechanisms of mitochondrial dynamics in energy metabolism after ischemic stroke, as well as new strategies to restore energy homeostasis and neural function. Through this, we hope to uncover new therapeutic targets for the treatment of ischemic stroke.

Glymphatic System in the Central Nervous System, a Novel Therapeutic Direction Against Brain Edema After Stroke.

Stroke is the destruction of brain function and structure, and is caused by either cerebrovascular obstruction or rupture. It is a disease associated with high mortality and disability worldwide. Brain edema after stroke is an important factor affecting neurologic function recovery. The glymphatic system is a recently discovered cerebrospinal fluid (CSF) transport system. Through the perivascular space and aquaporin 4 (AQP4) on astrocytes, it promotes the exchange of CSF and interstitial fluid (ISF), clears brain metabolic waste, and maintains the stability of the internal environment within the brain. Excessive accumulation of fluid in the brain tissue causes cerebral edema, but the glymphatic system plays an important role in the process of both intake and removal of fluid within the brain. The changes in the glymphatic system after stroke may be an important contributor to brain edema. Understanding and targeting the molecular mechanisms and the role of the glymphatic system in the formation and regression of brain edema after stroke could promote the exclusion of fluids in the brain tissue and promote the recovery of neurological function in stroke patients. In this review, we will discuss the physiology of the glymphatic system, as well as the related mechanisms and therapeutic targets involved in the formation of brain edema after stroke, which could provide a new direction for research against brain edema after stroke.

The Application of Brain Organoid Technology in Stroke Research: Challenges and Prospects.

Stroke is a neurological disease responsible for significant morbidity and disability worldwide. However, there remains a dearth of effective therapies. The failure of many therapies for stroke in clinical trials has promoted the development of human cell-based models, such as brain organoids. Brain organoids differ from pluripotent stem cells in that they recapitulate various key features of the human central nervous system (CNS) in three-dimensional (3D) space. Recent studies have demonstrated that brain organoids could serve as a new platform to study various neurological diseases. However, there are several limitations, such as the scarcity of glia and vasculature in organoids, which are important for studying stroke. Herein, we have summarized the application of brain organoid technology in stroke research, such as for modeling and transplantation purposes. We also discuss methods to overcome the limitations of brain organoid technology, as well as future prospects for its application in stroke research. Although there are many difficulties and challenges associated with brain organoid technology, it is clear that this approach will play a critical role in the future exploration of stroke treatment.

Preconditioning increases brain resistance against acute brain injury via neuroinflammation modulation.

Acute brain injury (ABI) is a broad concept mainly comprised of sudden parenchymal brain injury. Acute brain injury outcomes are dependent not only on the severity of the primary injury, but the delayed secondary injury that subsequently follows as well. These are both taken into consideration when determining the patient's prognosis. Growing clinical and experimental evidence demonstrates that "preconditioning," a prophylactic approach in which the brain is exposed to various pre-injury stressors, can induce varying degrees of "tolerance" against the impact of the ABI by modulating neuroinflammation. In this review, we will summarize the pathophysiology of ABI, and discuss the involved mechanisms of neuroinflammation in ABI, as well as existing experimental and clinical studies demonstrating the efficacy of preconditioning methods in various types of ABI by modulating neuroinflammation.

The Role of Nanomaterials in Stroke Treatment: Targeting Oxidative Stress.

Stroke has a high rate of morbidity and disability, which seriously endangers human health. In stroke, oxidative stress leads to further damage to the brain tissue. Therefore, treatment for oxidative stress is urgently needed. However, antioxidative drugs have demonstrated obvious protective effects in preclinical studies, but the clinical studies have not seen breakthroughs. Nanomaterials, with their characteristically small size, can be used to deliver drugs and have demonstrated excellent performance in treating various diseases. Additionally, some nanomaterials have shown potential in scavenging reactive oxygen species (ROS) in stroke according to the nature of nanomaterials. The drugs' delivery ability of nanomaterials has great significance for the clinical translation and application of antioxidants. It increases drug blood concentration and half-life and targets the ischemic brain to protect cells from oxidative stress-induced death. This review summarizes the characteristics and progress of nanomaterials in the application of antioxidant therapy in stroke, including ischemic stroke, hemorrhagic stroke, and neural regeneration. We also discuss the prospect of nanomaterials for the treatment of oxidative stress in stroke and the challenges in their application, such as the toxicity and the off-target effects of nanomaterials.

Insight Into the Mechanisms and the Challenges on Stem Cell-Based Therapies for Cerebral Ischemic Stroke.

Strokes are the most common types of cerebrovascular disease and remain a major cause of death and disability worldwide. Cerebral ischemic stroke is caused by a reduction in blood flow to the brain. In this disease, two major zones of injury are identified: the lesion core, in which cells rapidly progress toward death, and the ischemic penumbra (surrounding the lesion core), which is defined as hypoperfusion tissue where cells may remain viable and can be repaired. Two methods that are approved by the Food and Drug Administration (FDA) include intravenous thrombolytic therapy and endovascular thrombectomy, however, the narrow therapeutic window poses a limitation, and therefore a low percentage of stroke patients actually receive these treatments. Developments in stem cell therapy have introduced renewed hope to patients with ischemic stroke due to its potential effect for reversing the neurological sequelae. Over the last few decades, animal tests and clinical trials have been used to treat ischemic stroke experimentally with various types of stem cells. However, several technical and ethical challenges must be overcome before stem cells can become a choice for the treatment of stroke. In this review, we summarize the mechanisms, processes, and challenges of using stem cells in stroke treatment. We also discuss new developing trends in this field.

Clinical Outcome After Microsurgical Resection of Central Neurocytoma: A Single-Centre Analysis of 15 Years.

Objective: This study aimed to explore the immediate postoperative and long-term outcomes of central neurocytoma (CN) based on 15 years of experience in our institution. Methods: This single-institution study collected data of 43 patients with CN who underwent surgery between 2005 and 2020. We reviewed data of clinical, immediate postoperative outcome, and long-term outcome of patients. More specifically, we divided complications into neurological and regional complications groups. Results: Among the 43 patients with CN who underwent surgery, the transcortical (72.1%) or transcallosal (25.6%) approach was used. There were 18 patients (41.9%) who complained about postoperative neurological complications, including motor weakness (25.6%), memory deficit (18.6%), aphasia (7.0%), and seizure (4.7%). In addition, 18 patients suffered postoperative regional complications such as hydrocephalus (2.3%), hematoma (34.9%), infection (4.7%), and subcutaneous hydrops (2.3%). Only one-quarter of patients had suffered permanent surgical complications. The majority of patients recovered from the deficit and could turn back to normal life. There were no significant differences in the clinical outcomes between transcortical and transcallosal approaches. At a median follow-up of 61.8 months, the 5-year overall survival and progression-free survival were 87.0 and 74.0%, respectively. A multivariate Cox model analysis showed that the extent of resection was not related to progression-free survival. However, the extent of resection was significantly associated with overall survival, and gross total resection decreased the risk of death. Conclusions: Patients with CN show favorable outcomes after surgery. The transcortical and transcallosal approaches have similar postoperative complication rates and long-term follow-up outcomes. In terms of long-term prognosis, maximal safety resection should be the first choice of CN.

The Role of Iron, Its Metabolism and Ferroptosis in Traumatic Brain Injury.

Traumatic brain injury (TBI) is a structural and physiological disruption of brain function caused by external forces. It is a major cause of death and disability for patients worldwide. TBI includes both primary and secondary impairments. Iron overload and ferroptosis highly involved in the pathophysiological process of secondary brain injury. Ferroptosis is a form of regulatory cell death, as increased iron accumulation in the brain leads to lipid peroxidation, reactive oxygen species (ROS) production, mitochondrial dysfunction and neuroinflammatory responses, resulting in cellular and neuronal damage. For this reason, eliminating factors like iron deposition and inhibiting lipid peroxidation may be a promising therapy. Iron chelators can be used to eliminate excess iron and to alleviate some of the clinical manifestations of TBI. In this review we will focus on the mechanisms of iron and ferroptosis involving the manifestations of TBI, broaden our understanding of the use of iron chelators for TBI. Through this review, we were able to better find novel clinical therapeutic directions for further TBI study.

Surgical treatment of traumatic distal anterior cerebral artery aneurysm: a report of nine cases from a single centre.

BACKGROUND: Traumatic distal anterior cerebral artery (dACA) aneurysm is rare and can be easily neglected and misdiagnosed in patients with trauma. The aim of this study was to explore the radiologic characteristics of and therapeutic strategies for traumatic dACA aneurysm and to improve our understanding of unusual complications after trauma. METHODS: The clinical data of nine cases of traumatic dACA aneurysm from our neurosurgical department from July 1, 2010, to July 1, 2018, were retrospectively analysed. RESULTS: All 9 patients had a history of brain trauma. The initial computed tomography scan immediately after trauma showed subarachnoid haemorrhage in 8 cases. Among these cases, delayed intracranial haemorrhage occurred in 7 cases. The average interval between injury and diagnosis was 13.67 ± 9.43 days. All 9 cases were confirmed as traumatic dACA aneurysm by computed tomography angiography (CTA) and/or digital subtraction angiography. According to Lehecka's classification system, traumatic dACA aneurysm located in the A3 and A4 segment was found in 3 and 6 cases, respectively. Surgical treatment was performed in 8 cases, including neck clipping, with or without wrapping in 3 cases, trapping in 4 cases, aneurysm excision and suturing in 1 case and conservative treatment in 1 case. Three patients required a ventriculoperitoneal shunt due to severe hydrocephalus. According to the Glasgow Outcome Scale scoring system, good recovery was achieved in 4 cases, moderate disability in 2 cases, severe disability in 1 case, and death in 2 cases. CONCLUSION: Traumatic dACA aneurysm is a rare complication of brain trauma. Delayed intracranial haemorrhage and the sudden deterioration of neurologic function were the typical characteristics in patients with traumatic dACA aneurysm. CTA is the first-line screening modality for patients who present with intracerebral haemorrhage in the corpus callosum after trauma, particularly for patients who are older, in a poorer or critical condition. When the aneurysm is located in the A4 segment or involves a small branch, surgical trapping is the preferred definitive therapy to prevent further growth and disastrous bleeding. Early diagnosis and prompt treatment could help to improve clinical outcomes.

Correction to: Surgical treatment of traumatic distal anterior cerebral artery aneurysm: a report of nine cases from a single centre.

Incorrect family name of Dongsheng Guo.

Intracranial subarachnoid hemorrhage resulting from non-cervical spinal arteriovenous lesions: Analysis of possible cause of bleeding and literature review.

Subarachnoid hemorrhage (SAH) or intraventricle hemorrhage (IVH) with negative cerebral digital subtraction angiography (DSA) results, which are due to non-cervical spinal arteriovenous lesions, are uncommon. In this article we presented three cases from our hospital and nineteen cases from prior published literature and discussed clinical features, possible mechanisms underlying the hemorrhage and therapeutic strategies for managing this unusual entity. Our analysis revealed that headache was the most common initial symptom. Almost 60% of patients had symptoms related to the spinal cord at admission. Intramedullary arteriovenous malformations (AVM) were the most common type of malformation, and the thoracic segment was the most common location of the non-cervical spinal arteriovenous lesions. More than half of the patients had additional aneurysms. Surgery was chosen as the primary treatment modality in this series. Therefore, we speculate that thoracolumbar spinal arteriovenous lesions are an unusual cause of intracranial SAH with negative cerebral DSA results. If non-cervical spinal AVMs were associated with DSA-negative SAH, the pattern of hemorrhage could be manifested as the blood in supratentorial cisterns, the fourth ventricle or no copious blood around the foramen magnum as well (somewhat paradoxically), it depends on the timing of detection and image evaluation. The formation and the rupture of associated aneurysms were the most likely immediate cause of the intracranial SAH. If non-cervical spinal AVMs were not associated with DSA-negative SAH and all cases were genuine cases of 'SAH-of-unknown origin', the spinal AVM could be considered as incidental finding. Magnetic resonance imaging (MRI) of the complete spinal neuraxis is recommended to either exclude or identify a spinal lesion in these patients. Catheter-based spinal angiography remains the gold standard for the diagnosis of spinal vascular diseases. The decision regarding a therapeutic strategy is based on the angioarchitecture and on the type of spinal arteriovenous lesions.

Cerebral venous collaterals: A new fort for fighting ischemic stroke?

Stroke therapy has entered a new era highlighted by the use of endovascular therapy in addition to intravenous thrombolysis. However, the efficacy of current therapeutic regimens might be reduced by their associated adverse events. For example, over-reperfusion and futile recanalization may lead to large infarct, brain swelling, hemorrhagic complication and neurological deterioration. The traditional pathophysiological understanding on ischemic stroke can hardly address these occurrences. Accumulating evidence suggests that a functional cerebral venous drainage, the major blood reservoir and drainage system in brain, may be as critical as arterial infusion for stroke evolution and clinical sequelae. Further exploration of the multi-faceted function of cerebral venous system may add new implications for stroke outcome prediction and future therapeutic decision-making. In this review, we emphasize the anatomical and functional characteristics of the cerebral venous system and illustrate its necessity in facilitating the arterial infusion and maintaining the cerebral perfusion in the pathological stroke content. We then summarize the recent critical clinical studies that underscore the associations between cerebral venous collateral and outcome of ischemic stroke with advanced imaging techniques. A novel three-level venous system classification is proposed to demonstrate the distinct characteristics of venous collaterals in the setting of ischemic stroke. Finally, we discuss the current directions for assessment of cerebral venous collaterals and provide future challenges and opportunities for therapeutic strategies in the light of these new concepts.

Bosutinib Attenuates Inflammation via Inhibiting Salt-Inducible Kinases in Experimental Model of Intracerebral Hemorrhage on Mice.

BACKGROUND AND PURPOSE: Intracerebral hemorrhage (ICH) is a subtype of stroke with highest mortality and morbidity. Pronounced inflammation plays a significant role in the development of the secondary brain injury after ICH. Recently, SIK-2 (salt-inducible kinase-2) was identified as an important component controlling inflammatory response. Here we sought to investigate the role of SIK-2 in post-ICH inflammation and potential protective effects of SIK-2 inhibition after ICH. METHODS: Two hundred and ninety-three male CD-1 mice were used. ICH was induced via injection of 30 µL of autologous blood. Recombinant SIK-2 was administrated 1 hour after ICH intracerebroventricularly. SIK-2 small interfering RNA was injected intracerebroventricularly 24 hours before ICH. Bosutinib, a clinically approved tyrosine kinase inhibitor with affinity to SIK-2, was given intranasally 1 hour or 6 hours after ICH. Effects of treatments were evaluated by neurological tests and brain water content calculation. Molecular pathways were investigated by Western blots and immunofluorescence studies. RESULTS: Endogenous SIK-2 was expressed in microglia and neurons. SIK-2 expression was reduced after ICH. Exogenous SIK-2 aggravated post-ICH inflammation, leading to brain edema and the neurobehavioral deficits. SIK-2 inhibition attenuated post-ICH inflammation, reducing brain edema and ameliorating neurological dysfunctions. Bosutinib inhibited SIK-2-attenuating ICH-induced brain damage. Protective effects of Bosutinib were mediated, at least partly, by CRTC3 (cyclic amp-response element binding protein-regulated transcription coactivator 3)/cyclic amp-response element binding protein/NF-κB (nuclear factor-κB) pathway. CONCLUSIONS: SIK-2 participates in inflammation induction after ICH. SIK-2 inhibition via Bosutinib or small interfering RNA decreased inflammation, attenuating brain injury. SIK-2 effects are, at least partly, mediated by CRTC3-cyclic amp-response element binding protein-NF-κB signaling pathway.

Low-density lipoprotein receptor-related protein-1 facilitates heme scavenging after intracerebral hemorrhage in mice.

Heme-degradation after erythrocyte lysis plays an important role in the pathophysiology of intracerebral hemorrhage. Low-density lipoprotein receptor-related protein-1 is a receptor expressed predominately at the neurovascular interface, which facilitates the clearance of the hemopexin and heme complex. In the present study, we investigated the role of low-density lipoprotein receptor-related protein-1 in heme removal and neuroprotection in a mouse model of intracerebral hemorrhage. Endogenous low-density lipoprotein receptor-related protein-1 and hemopexin were increased in ipsilateral brain after intracerebral hemorrhage, accompanied by increased hemoglobin levels, brain water content, blood-brain barrier permeability and neurological deficits. Exogenous human recombinant low-density lipoprotein receptor-related protein-1 protein reduced hematoma volume, brain water content surrounding hematoma, blood-brain barrier permeability and improved neurological function three days after intracerebral hemorrhage. The expression of malondialdehyde, fluoro-Jade C positive cells and cleaved caspase 3 was increased three days after intracerebral hemorrhage in the ipsilateral brain tissues and decreased with recombinant low-density lipoprotein receptor-related protein-1. Intracerebral hemorrhage decreased and recombinant low-density lipoprotein receptor-related protein-1 increased the levels of superoxide dismutase 1. Low-density lipoprotein receptor-related protein-1 siRNA reduced the effect of human recombinant low-density lipoprotein receptor-related protein-1 on all outcomes measured. Collectively, our findings suggest that low-density lipoprotein receptor-related protein-1 contributed to heme clearance and blood-brain barrier protection after intracerebral hemorrhage. The use of low-density lipoprotein receptor-related protein-1 as supplement provides a novel approach to ameliorating intracerebral hemorrhage brain injury via its pleiotropic neuroprotective effects.

Recombinant Gas6 augments Axl and facilitates immune restoration in an intracerebral hemorrhage mouse model.

Axl, a tyrosine kinase receptor, was recently identified as an essential component regulating innate immune response. Suppressor of cytokine signaling 1 and suppressor of cytokine signaling 3 are potent Axl-inducible negative inflammatory regulators. This study investigated the role of Axl signaling pathway in immune restoration in an autologous blood-injection mouse model of intracerebral hemorrhage. Recombinant growth arrest-specific 6 (Gas6) and R428 were administrated as specific agonist and antagonist. In vivo knockdown of Axl or suppressor of cytokine signaling 1 and suppressor of cytokine signaling 3 by siRNA was applied. After intracerebral hemorrhage, the expression of endogenous Axl, soluble Axl, and Gas6 was increased, whereas the expression of suppressor of cytokine signaling 1 and suppressor of cytokine signaling 3 was inhibited. Recombinant growth arrest-specific 6 administration alleviated brain edema and improved neurobehavioral performances. Moreover, enhanced Axl phosphorylation with cleavage of soluble Axl (sAxl), and an upregulation of suppressor of cytokine signaling 1 and suppressor of cytokine signaling 3 were observed. In vivo knockdown of Axl and R428 administration both abolished the effect of recombinant growth arrest-specific 6 on brain edema and also decreased the expression suppressor of cytokine signaling 1 and suppressor of cytokine signaling 3. In vivo knockdown of suppressor of cytokine signaling 1 and suppressor of cytokine signaling 3 aggravated cytokine releasing despite of recombinant growth arrest-specific 6. In conclusion, Axl plays essential role in immune restoration after intracerebral hemorrhage. And recombinant growth arrest-specific 6 attenuated brain injury after intracerebral hemorrhage, probably by enhancing Axl phosphorylation and production of suppressor of cytokine signaling 1 and suppressor of cytokine signaling 3.

Elderly Patients with Severe Traumatic Brain Injury Could Benefit from Surgical Treatment.

OBJECTIVE: In elderly patients with severe traumatic brain injury, the use of aggressive versus conservative management remains controversial. The aim of this study was to assess the outcome of surgical alternatives for treatment of severe traumatic intracranial hematoma in patients ≥65 years old and identify factors that may contribute to the outcome. METHODS: This retrospective study included 112 patients with traumatic intracranial hematoma. Logistic regression analysis was used to identify independent predictors of unfavorable outcome. The Glasgow Outcome Scale was used to evaluate the outcome. RESULTS: Surgery was performed in 70 (62.5%) patients ≥65 years old. A favorable outcome occurred in 33 (47.1%) surgical patients, and 23 (32.9%) surgical patients died. Patients who underwent surgery were less likely to have an unfavorable outcome (52.9% vs. 95.2%) and less likely to die (32.9% vs. 88.1%) at 6 months postinjury compared with patients treated conservatively. Multivariate logistic regression analysis revealed that lower Glasgow Coma Scale score (≤5) was a significant factor associated with unfavorable outcome (odds ratio [OR] = 18.7, 95% confidence interval [CI] = 5.2-95.5, P < 0.001) and mortality (OR = 10.7, 95% CI = 4.4-28.5, P < 0.001). However, neurosurgical intervention was a significant factor to negatively predict unfavorable outcome (OR = 0.03, 95% CI = 0.01-0.1, P < 0.001) and mortality (OR = 0.04, 95% CI = 0.01-0.1, P < 0.001). CONCLUSIONS: This study showed that Glasgow Coma Scale score (≤5) was a major determinant of outcome in elderly patients with severe traumatic brain injury. However, surgical treatment reduced mortality and improved outcome in the elderly patients in this study.

Lipoxin A4 Reduces Inflammation Through Formyl Peptide Receptor 2/p38 MAPK Signaling Pathway in Subarachnoid Hemorrhage Rats.

BACKGROUND AND PURPOSE: Lipoxin A4 (LXA4) has been reported to reduce inflammation in several neurological injury models. We studied the effects of LXA4 on neuroinflammation after subarachnoid hemorrhage (SAH) in a rat model. METHODS: Two hundred and thirty-eight Sprague-Dawley male rats, weight 280-320 g, were used. Exogenous LXA4 (0.3 and 1.0 nmol) were injected intracerebroventricularly at 1.5 hours after SAH. Neurological scores, brain water content, and blood-brain barrier were evaluated at 24 hours after SAH; Morris water maze and T-maze tests were examined at 21 days after SAH. The expression of endogenous LXA4 and its receptor formyl peptide receptor 2 (FPR2), as well as p38, interleukin-1ß, and interleukin-6 were studied either by ELISA or by Western blots. Neutrophil infiltration was observed by myeloperoxidase staining. FPR2 siRNA was used to knock down LXA4 receptor. RESULTS: The expression of endogenous LXA4 decreased, and the expression of FPR2 increased after SAH. Exogenous LXA4 decreased brain water content, reduced Evans blue extravasation, and improved neurological functions and improved the learning and memory ability after SAH. LXA4 reduced neutrophil infiltration and phosphorylation of p38, interleukin-1ß, and interleukin-6. These effects of LXA4 were abolished by FPR2 siRNA. CONCLUSIONS: Exogenous LXA4 inhibited inflammation by activating FPR2 and inhibiting p38 after SAH. LXA4 may serve as an alternative treatment to relieve early brain injury after SAH.