Sulfated Polysaccharide-Based Nanocarrier Drives Microenvironment-Mediated Cerebral Neurovascular Remodeling for Ischemic Stroke Treatment.

Stroke is a leading cause of global mortality and severe disability. However, current strategies used for treating ischemic stroke lack specific targeting capabilities, exhibit poor immune escape ability, and have limited drug release control. Herein, we developed an ROS-responsive nanocarrier for targeted delivery of the neuroprotective agent rapamycin (RAPA) to mitigate ischemic brain damage. The nanocarrier consisted of a sulfated chitosan (SCS) polymer core modified with a ROS-responsive boronic ester enveloped by a red blood cell membrane shell incorporating a stroke homing peptide. When encountering high levels of intracellular ROS in ischemic brain tissues, the release of SCS combined with RAPA from nanoparticle disintegration facilitates effective microglia polarization and, in turn, maintains blood-brain barrier integrity, reduces cerebral infarction, and promotes cerebral neurovascular remodeling in a mouse stroke model involving transient middle cerebral artery occlusion (tMCAO). This work offers a promising strategy to treat ischemic stroke therapy.

Surface-tethered ROS-responsive micelle backpacks for boosting mesenchymal stem cell vitality and modulating inflammation in ischemic stroke treatment.

Mesenchymal stem cells (MSCs) exhibited remarkable therapeutic potential in ischemic stroke due to their exceptional immunomodulatory ability and paracrine effect; they have also been regarded as excellent neuroprotectant delivery vehicles with inflammatory tropism. However, the presence of high levels of reactive oxygen species (ROS) and an oxidative stress environment at the lesion site inhibits cell survival and further therapeutic effects. Using bioorthogonal click chemistry, ROS-responsive luteolin-loaded micelles were tethered to the surface of MSCs. As MSCs migrated to the ischemic brain, the micelles would achieve ROS-responsive release of luteolin to protect MSCs from excessive oxidative damage while inhibiting neuroinflammation and scavenging ROS to ameliorate ischemic stroke. This study provided an effective and prospective therapeutic strategy for ischemic stroke and a framework for a stem cell-based therapeutic system to treat inflammatory cerebral diseases.

Tailored Apoptotic Vesicle Delivery Platform for Inflammatory Regulation and Tissue Repair to Ameliorate Ischemic Stroke.

Apoptotic vesicles (ApoVs) hold great promise for inflammatory regulation and tissue repair. However, little effort has been dedicated to developing ApoV-based drug delivery platforms, while the insufficient targeting capability of ApoVs also limits their clinical applications. This work presents a platform architecture that integrates apoptosis induction, drug loading, and functionalized proteome regulation, followed by targeting modification, enabling the creation of an apoptotic vesicle delivery system to treat ischemic stroke. Briefly, α-mangostin (α-M) was utilized to induce mesenchymal stem cell (MSC) apoptosis while being loaded onto MSC-derived ApoVs as an anti-oxidant and anti-inflammatory agent for cerebral ischemia/reperfusion injury. Matrix metalloproteinase activatable cell-penetrating peptide (MAP), a microenvironment-responsive targeting peptide, was modified on the surface of ApoVs to obtain the MAP-functionalized α-M-loaded ApoVs. Such engineered ApoVs targeted the injured ischemic brain after systemic injection and achieved an enhanced neuroprotective activity due to the synergistic effect of ApoVs and α-M. The internal protein payloads of ApoVs, upon α-M activation, were found engaged in regulating immunological response, angiogenesis, and cell proliferation, all of which contributed to the therapeutic effects of ApoVs. The findings provide a universal framework for creating ApoV-based therapeutic drug delivery systems for the amelioration of inflammatory diseases and demonstrate the potential of MSC-derived ApoVs to treat neural injury.

VCAM-1-binding peptide targeted cationic liposomes containing NLRP3 siRNA to modulate LDL transcytosis as a novel therapy for experimental atherosclerosis.

BACKGROUND: Activation of NLRP3 inflammasome accelerates the formation of atherosclerotic plaques. Here, we evaluated the effects of inflammation on the expression of the NLRP3 inflammasome in endothelial cells (ECs). METHODS: The effect of TNF-α on transcytosis of LDL was measured. VCAM-1 binding peptide targeting cationic liposomes (PCLs) were prepared as siRNA vectors. Methylated NLRP3 siRNA was encapsulated into the PCLs to knock down NLRP3 in vitro and in vivo. In rats with partial carotid ligation, TNF-α-induced LDL retention in the carotid artery endothelium was observed. In ApoE-/- mice, NLRP3 siRNA-PCLs were injected intravenously to observe their effect on the formation of atherosclerosis. RESULTS: Our results showed that TNF-α upregulated NLRP3 in ECs, promoting the assembly of the NLRP3 inflammasome and processing of pro-IL-1ß into IL-1ß. Moreover, TNF-α accelerated LDL transcytosis in ECs. Knockdown of NLRP3 prevented TNF-α-induced NLPR3 inflammasome/IL-1ß signaling and LDL transcytosis. Using optimized cationic liposomes to encapsulate methylated NLRP3 siRNA, resulting in targeting of VCAM-1-expressing ECs, to knockdown NLRP3, TNF-α-induced NLRP3 inflammasome activation and LDL transcytosis were prevented. Using the partial carotid ligation as an atherosclerosis rat model, we found that local administration of NLRP3 siRNA-PCLs efficiently knocked down NLPR3 expression in the carotid endothelium and dramatically attenuated the deposition of atherogenic LDL in carotid ECs in TNF-α-challenged rats. Furthermore, NLRP3 siRNA-PCLs were injected intravenously in ApoE-/- mice, resulting in reduced plaque formation. CONCLUSION: These findings established a novel strategy for targeting the NLRP3 inflammasome using NLRP3 siRNA-PCLs to interrupt LDL transcytosis, representing a potential novel therapy for atherosclerosis.

Multicentric Glioma: An Ideal Model to Reveal the Mechanism of Glioma.

As a special type of glioma, multicentric glioma provides an ideal pathological model for glioma research. According to the stem-cell-origin theory, multiple lesions of multicentric glioma share the same neuro-oncological origin, both in gene level and in cell level. Although the number of studies focusing on genetic evolution in gliomas with the model of multicentric gliomas were limited, some mutations, including IDH1 mutations, TERTp mutations and PTEN deletions, are found to be at an early stage in the process of genetic aberrance during glioma evolution based on the results of these studies. This article reviews the clinical reports and genetic studies of multicentric glioma, and intends to explain the various clinical phenomena of multicentric glioma from the perspective of genetic aberrance accumulation and tumor cell evolution. The malignant degree of a glioma is determined by both the tumorigenicity of early mutant genes, and the stemness of early suffered cells.

A Non-Isocyanate Route to Poly(Ether Urethane): Synthesis and Effect of Chemical Structures of Hard Segment.

A series of non-isocyanate poly(ether urethane) (PEU) were prepared by an environmentally friendly route based on dimethyl carbonate, diols and a polyether. The effect of the chemical structure of polyurethane hard segments on the properties of this kind of PEU was systematically investigated in this work. Polyurethane hard segments with different structures were first prepared from hexamethylene di-carbamate (BHC) and different diols (butanediol, hexanediol, octanediol and decanediol). Subsequently, a series of non-isocyanate PEU were obtained by polycondensation of the polyurethane hard segments with the polyether soft segments (PTMG2000). The PEU were characterized by GPC, FT-IR, 1H NMR, DSC, WAXD, SAXS, AFM and tensile testing. The results show that the urea groups generated by the side reaction affect the degree of crystallization of hard segments by influencing the hydrogen bonding of the hard segments molecular chains. The degree of hard segment crystallization, in turn, affects the thermal and mechanical properties of the polymer. The urea group content is related to the carbon chain length of the diol used for the synthesis of hard segments. When butanediol is applied to synthesize hard segment, the hard segment of the resulting PEU is unable to crystallize. Therefore, the tensile strength and modulus of elasticity of butanediol-based PEU is lowest among three, though it possesses the highest urea group content. When longer octanediol or decanediol is applied to synthesize the hard segment, the hard segments in the resulting polyether-based polyurethane are crystallizable and the resulting PEU possesses higher tensile strength.

microRNA-455-5p alleviates neuroinflammation in cerebral ischemia/reperfusion injury.

Neuroinflammation is a major pathophysiological factor that results in the development of brain injury after cerebral ischemia/reperfusion. Downregulation of microRNA (miR)-455-5p after ischemic stroke has been considered a potential biomarker and therapeutic target for neuronal injury after ischemia. However, the role of miR-455-5p in the post-ischemia/reperfusion inflammatory response and the underlying mechanism have not been evaluated. In this study, mouse models of cerebral ischemia/reperfusion injury were established by transient occlusion of the middle cerebral artery for 1 hour followed by reperfusion. Agomir-455-5p, antagomir-455-5p, and their negative controls were injected intracerebroventricularly 2 hours before or 0 and 1 hour after middle cerebral artery occlusion (MCAO). The results showed that cerebral ischemia/reperfusion decreased miR-455-5p expression in the brain tissue and the peripheral blood. Agomir-455-5p pretreatment increased miR-455-5p expression in the brain tissue, reduced the cerebral infarct volume, and improved neurological function. Furthermore, primary cultured microglia were exposed to oxygen-glucose deprivation for 3 hours followed by 21 hours of reoxygenation to mimic cerebral ischemia/reperfusion. miR-455-5p reduced C-C chemokine receptor type 5 mRNA and protein levels, inhibited microglia activation, and reduced the production of the inflammatory factors tumor necrosis factor-α and interleukin-1ß. These results suggest that miR-455-5p is a potential biomarker and therapeutic target for the treatment of cerebral ischemia/reperfusion injury and that it alleviates cerebral ischemia/reperfusion injury by inhibiting C-C chemokine receptor type 5 expression and reducing the neuroinflammatory response.

Exposure region of the Kawase approach and its correlation with skull base anatomy: An evaluation with digital models.

The Kawase approach is one of the most used trajectories in skull base surgery. The exposure range of the approach and its correlation with skull base anatomy still demand more exploration. With the help of digital rebuilding, analysis, and measurement, we evaluated the exposure range of the Kawase and extended Kawase approaches and analyzed the correlation between the exposure range and the variants of the petrosal and clival anatomy. The finding of the study demonstrated that compared to the sub-temporal approach, the Kawase approach and the extended Kawase approach significantly added the exposure range in the upper, middle, and partial inferior regions of the clivus. The gains in the exposure volume and area are more when the manipulation angle is less than 135°.

Imaging Acute Stroke: From One-Size-Fit-All to Biomarkers.

In acute stroke management, time window has been rigidly used as a guide for decades and the reperfusion treatment is only available in the first few limited hours. Recently, imaging-based selection of patients has successfully expanded the treatment window out to 16 and even 24 h in the DEFUSE 3 and DAWN trials, respectively. Recent guidelines recommend the use of imaging techniques to guide therapeutic decision-making and expanded eligibility in acute ischemic stroke. A tissue window is proposed to replace the time window and serve as the surrogate marker for potentially salvageable tissue. This article reviews the evolution of time window, addresses the advantage of a tissue window in precision medicine for ischemic stroke, and discusses both the established and emerging techniques of neuroimaging and their roles in defining a tissue window. We also emphasize the metabolic imaging and molecular imaging of brain pathophysiology, and highlight its potential in patient selection and treatment response prediction in ischemic stroke.

Preferential Targeting Cerebral Ischemic Lesions with Cancer Cell-Inspired Nanovehicle for Ischemic Stroke Treatment.

The poor drug delivery to cerebral ischemic regions is a key challenge of ischemic stroke treatment. Inspired by the intriguing blood-brain barrier (BBB)-penetrating ability of 4T1 cancer cells upon their brain metastasis, we herein designed a promising biomimetic nanoplatform by camouflaging a succinobucol-loaded pH-sensitive polymeric nanovehicle with a 4T1 cell membrane (MPP/SCB), aiming to promote the preferential targeting of cerebral ischemic lesions to attenuate the ischemia/reperfusion injury. In transient middle cerebral artery occlusion (tMCAO) rat models, MPP/SCB could be preferentially delivered to the ischemic hemisphere with a 4.79-fold higher than that in the normal hemisphere. Moreover, MPP/SCB produced notable enhancement of microvascular reperfusion in the ischemic hemisphere, resulting in a 69.9% reduction of infarct volume and showing remarkable neuroprotective effects of tMCAO rats, which was superior to the counterpart uncamouflaged nanovehicles (PP/SCB). Therefore, this design provides a promising nanoplatform to target the cerebral ischemic lesions for ischemic stroke therapy.

Hydrogen inhibits microglial activation and regulates microglial phenotype in a mouse middle cerebral artery occlusion model.

Microglia participate in bi-directional control of brain repair after stroke. Previous studies have demonstrated that hydrogen protects brain after ischemia/reperfusion (I/R) by inhibiting inflammation, but the specific mechanism of anti-inflammatory effect of hydrogen is poorly understood. The goal of our study is to investigate whether inhalation of high concentration hydrogen (HCH) is able to attenuate I/R-induced microglia activation. Eighty C57B/L male mice were divided into four groups: sham, I/R, I/R + HCH and I/R + N2/O2 groups. Assessment of animals happened in "blind" matter. I/R was induced by occlusion of middle cerebral artery for one hour). After one hour, filament was withdrawn, which induced reperfusion. Hydrogen treated I/R animals inhaled mix of 66.7% H2 balanced with O2 for 90 minutes, starting immediately after initiation of reperfusion. Control animals (N2/O2) inhaled mix in which hydrogen was replaced with N2 for the same time (90 minutes). The brain injury, such as brain infarction and development of brain edema, as well as neurobehavioral deficits were determined 23 hours after reperfusion. Effect of HCH on microglia activation in the ischemic penumbra was investigated by immunostaining also 23 hours after reperfusion. mRNA expression of inflammation related genes was detected by PCR. Our results showed that HCH attenuated brain injury and consequently reduced neurological dysfunction after I/R. Furthermore, we demonstrated that HCH directed microglia polarization towards anti-inflammatory M2 polarization. This study indicates hydrogen may exert neuroprotective effects by inhibiting the microglial activation and regulating microglial polarization. This study was conducted in agreement with the Animal Care and Use Committee (IACUC) and Institutional Animal Care guidelines regulation (Shanghai Jiao Tong University, China (approval No. A2015-011) in November 2015.

Serotonergically dependent antidepressant-like activity on behavior and stress axis responsivity of acacetin.

Acacetin, a natural flavonoid, possesses broad spectrum of pharmacological and biochemical activities, such as neuroprotection, antinociception and inhibition of monoamine oxidase. The current work aimed to investigate the antidepressant-like activity of acacetin in mice and explore the underlying mechanism(s). Chronic, but not acute, acacetin treatment (5, 15 or 45 mg/kg, p.o., once per day for three weeks) exerted in mice dose-dependently antidepressant-like activity, assessed by forced swim test (FST) and tail suspension test (TST). Although acacetin-treated mice showed normal circadian hypothalamo-pituitary-adrenal (HPA) axis activity, their endocrine responsivity to both acute restraint stress and intracerebroventricular injection of corticotropin-releasing factor (CRF) was buffered. The acacetin-triggered antidepressant-like activities are serotonergically dependent, since its impacts on behavior and stress responsivity were totally abolished by chemical depletion of brain serotonin by PCPA. Consistently, acacetin-treated mice showed escalated levels of brain monoamines especially serotonin and depressed activity of monoamine oxidase. Moreover, the acacetin-evoked anti-depression was preferentially counteracted by co-administration of 5-HT1A receptor antagonist WAY-100635, but potentiated by 5-HT1A receptor agonist 8-OH-DPAT and sub-effective dose of serotonergic antidepressant fluoxetine, suggesting a pivotal engagement of 5-HT1A related serotonergic system. In vitro, acacetin (1-100 nM) increased the Emax of 8-OH-DPAT. Collectively, these findings confirm that chronic acatetin administration to mice engenders antidepressant-like efficacy on both behavior and stress axis responsivity, with serotonergic system that preferentially couples with 5-HT1A receptors being critically involved.

MicroRNA-132 attenuates cerebral injury by protecting blood-brain-barrier in MCAO mice.

MicroRNAs (miRNAs) have been widely reported to induce posttranscriptional gene silencing and led to an explosion of new strategies for the treatment of human disease. It has been reported that the expression of MicroRNA-132 (miR-132) are altered both in the blood and brain after stroke. However, the effect of miR-132 on blood-brain barrier (BBB) disruption in ischemia stroke has not been studied. Here we will investigate the effects of miR-132 on the permeability of BBB after ischemic stroke and explore the potential mechanism underlying observed protection. Eight week-old mice were injected intracerebroventricularly with miR-132, antagomir-132 or agomir negative control (agomir-NC) 2 h before middle cerebral artery occlusion (MCAO), followed by animal behavior tests and infraction volume measurement at 24 h after MCAO. BBB permeability and integrity were measured by Evan's blue extravasation and brain water content. The expression of tight junction proteins was detected by immnostaining and Western blots. The level of MiR-132 and its targeted gene Mmp9 were assayed. Treatment with exogenous MiR-132 (agomir-132) decreased the infraction volume, reduced brain edema, and improved neurological functions compared to control mice. Agomir-132 increased the level of MiR-132 in brain tissue, suppressed the expression of MMP-9 mRNA and decreased the degradation of tight junction proteins VE-cadherin and ß-Catenin in ischemic stroke mice. Inhibition of MMP-9 has a similar protective effect to agomir-132 on infraction volume, brain edema, and tight-junction protein expression after MCAO. Our results indicated that miR-132/MMP-9 axis might be a novel therapeutic target for BBB protection in ischemic stroke.

Potential of Exosomes for the Treatment of Stroke.

Stroke is the result of blockage or rupture of blood vessels in the brain and is the leading cause of death and disability in the world. Currently only a very limited number of therapeutic approaches are available for treatment of stroke patients, and the vast majority of neuroprotective agents that tested positively in pre-clinical studies failed in clinical trials. In recent years, the clinical value of the use of exosomes for stroke treatment has received widespread attention due their unique characteristics such as low immunogenicity, low toxicity and biodegradability, ability to cross the blood-brain barrier (BBB), and their important role in communication between cells. More and more evidence suggests that the secretion of exosomes is the mechanism underlying the protection induced by mesenchymal stromal cells (MSCs) after stroke. Exosomes are thought to support brain restoration and induce repairing effects, including neurovascular remodeling, and anti-apoptosis and anti-inflammatory effects. Recent reports have focused on the clinical application of exosomes as a potential drug delivery approach. This review focuses on the ability of exosomes to interrupt the stroke-induced pathologic processes of stroke, and on publications describing how to achieve more effective treatment of stroke with exosomes.

Chronic itch impairs mood and HPA axis function in mice: modulation by CRFR1 antagonist.

Chronic itch is clinically correlated with the development of mood disorders such as anxiety and depression. Nonetheless, whether this relevance exists in rodents is unknown, and evidence demonstrating chronic itch can affect mood is lacking. The aim of this study is to characterize the affective consequences of chronic itch, and explore potential mechanisms and interventional strategy. We subjected mice to chronic itch by repetitive cutaneous treatment with acetone and diethylether followed by water (AEW) that models "dry skin." After 3 to 4 weeks AEW treatment, the mice developed behavioral phenotypes of anxiety and depression assessed by a battery of behavioral paradigms, such as light-dark box and forced swim test. These behavioral symptoms of mood disturbance were independent of cutaneous barrier disruption, but correlated well with the degree of the irritating itch sensation. Although AEW mice showed normal circadian hypothalamic-pituitary-adrenal (HPA) axis activity, their neuroendocrine functionality was dampened, including impaired endocrine stress responsivity, altered neuroendocrine-immune interaction, and blunted corticosterone response to both dexamethasone and CRF. Parameters of HPA functionality at the level of mRNA transcripts are altered in stress-related brain regions of AEW mice, implying an overdrive of central CRF system. Remarkably, chronic treatment of AEW mice with antalarmin, a CRFR1 antagonist, ameliorated both their mood impairment and stress axis dysfunction. This is the first evidence revealing mood impairment, HPA axis dysfunction, and potential therapeutic efficacy by CRFR1 antagonist in mice with chronic itch, thus providing a preclinical model to investigate the affective consequence of chronic itch and the underlying mechanisms.

Advances in stroke pharmacology.

Stroke occurs when a cerebral blood vessel is blocked or ruptured, and it is the major cause of death and adult disability worldwide. Various pharmacological agents have been developed for the treatment of stroke either through interrupting the molecular pathways leading to neuronal death or enhancing neuronal survival and regeneration. Except for rtPA, few of these agents have succeeded in clinical trials. Recently, with the understanding of the pathophysiological process of stroke, there is a resurrection of research on developing neuroprotective agents for stroke treatment, and novel molecular targets for neuroprotection and neurorestoration have been discovered to predict or offer clinical benefits. Here we review the latest major progress of pharmacological studies in stroke, especially in ischemic stroke; summarize emerging potential therapeutic mechanisms; and highlight recent clinical trials. The aim of this review is to provide a panorama of pharmacological interventions for stroke and bridge basic and translational research to guide the clinical management of stroke therapy.

Combination of dura turning-over and decompressive craniectomy: a new pattern of surgery for cerebral infarction caused by craniocerebral gunshot injury.

BACKGROUND: Craniocerebral gunshot injury refers to a wound caused by a bullet passing through or lodged in brain tissue, resulting in the loss of function of a certain area or other fatal damage to the human brain. Craniocerebral gunshot injury is usually life-threatening and is very common in modern warfare, accounting for the majority of battle casualties. Most of the patients suffer from acute cerebral infarction caused by vascular injury. Lack of early and solid battlefield emergency medical interference adds to the risk of death among the wounded. CASE PRESENTATION: We present a 24-year-old man who was shot with a shotgun from a distance of 15 m in an accidental injury. Forty-seven grapeshots were found on his body surface by physical examination. A computed tomography (CT) scan demonstrated large areas of low-density shadows in his right parietal lobe and right temporal lobe with the midline shifting to the left side 2 days later. Afterwards, the patient was transferred to our emergency medical center at Changzheng Hospital in Shanghai. Cranial computed tomography angiography (CTA) showed a high-density shadow in the initial part of the right middle cerebral artery. The branches after the initial part were obliterated. Prompt medical attention and decompressive craniotomy (DC) surgery contributed to the final recovery from cerebral infarction of this patient. CONCLUSION: Bullets can penetrate or be lodged in the brain, causing intracranial hypertension. The bullets lodged in the brain can result in stenosis and embolism of a cerebral artery, causing acute cerebral infarction. Combining dura turning-over surgery with DC surgery can not only decrease intracranial pressure, which can increase the blood supply for hypertension-induced vessel stenosis, but also help vessels outside the dura mater grow into ischemic areas of the cerebral cortex. However, this new pattern of surgery needs further support from evidence-based medicine.

Secoisolariciresinol diglycoside, a flaxseed lignan, exerts analgesic effects in a mouse model of type 1 diabetes: Engagement of antioxidant mechanism.

Peripheral painful neuropathy is one of the most common complications in diabetes and necessitates improved treatment. Secoisolariciresinol diglycoside (SDG), a predominant lignan in flaxseed, has been shown in our previous studies to exert antidepressant-like effect. As antidepressant drugs are clinically used to treat chronic neuropathic pain, this work aimed to investigate the potential analgesic efficacy of SDG against diabetic neuropathic pain in a mouse model of type 1 diabetes. We subjected mice to diabetes by a single intraperitoneal (i.p.) injection of streptozotocin (STZ, 200 mg/kg), and Hargreaves test or von Frey test was used to assess thermal hyperalgesia or mechanical allodynia, respectively. Chronic instead of acute SDG treatment (3, 10 or 30 mg/kg, p.o., twice per day for three weeks) ameliorated thermal hyperalgesia and mechanical allodynia in diabetic mice, and these analgesic actions persisted about three days when SDG treatment was terminated. Although chronic treatment of SDG to diabetic mice did not impact on the symptom of hyperglycemia, it greatly attenuated excessive oxidative stress in sciatic nerve and spinal cord tissues, and partially counteracted the condition of weight decrease. Furthermore, the analgesic actions of SDG were abolished by co-treatment with the reactive oxygen species donor tert-butyl hydroperoxide (t-BOOH), but potentiated by the reactive oxygen species scavenger phenyl-N-tert-butylnitrone (PBN). These findings indicate that chronic SDG treatment can correct neuropathic hyperalgesia and allodynia in mice with type 1 diabetes. Mechanistically, the analgesic actions of SDG in diabetic mice may be associated with its antioxidant activity.

Surgical treatment achieves better outcome in severe traumatic pericallosal aneurysm: case report and literature review.

Traumatic pericallosal aneurysm (TPA) is typically seldom yet potentially lethal. Because of its rarity, also complicated by the unpredictable delayed-onset, TPA is more difficult to be diagnosed promptly. Due to the sporadic reports and diverse opinions on the priority of surgical treatment, a consensus about effective management of TPA has not been reached. Here we report a 55 year-old male patient with TPA, who received an emergent craniotomy to clip the pseudoaneurysm and remove the hematoma under intense intracranial pressure (ICP) monitoring. A satisfactory clinical outcome was achieved at a 3-month follow-up. Thereafter, a review was conducted to evaluate the outcomes of different managing modalities.