The Mechanism and Function of circlRP6 Targeting miR-145 in Occurrence of Intracranial Aneurysms.

Objective: To explore the differential expression of circLRP6 targeted miR-145 in intracranial aneurysms and its regulation of VSMC biological activity, providing a theoretical foundation for the study of intracranial aneurysm regulation by circLRP6. Methods: Expression levels of circLRP6 and miR-145 mRNA were measured in intracranial aneurysms and superficial temporal arteries. In vitro experiments were conducted using TNF-αstimulated HBVSMCs to evaluate the expression of circLRP6 and miR-145, as well as cell proliferation, apoptosis, migration, and related protein expression. Results: CircLRP6 was low expressed in intracranial aneurysms, and MiR-145 showed a trend of Overexpression; With the increase of circLRP6 expression in intracranial aneurysms, expression of miR-145 decreased. The correlation coefficient, r, was -0.5139; After TNF- α following stimulation, phenotype of VSMCs changed, expression of circLRP6 in cells decreased, and expression of miR-145 increased; CircLRP was successfully overexpressed or knocked out in VSMCs cells; Overexpression of circLRP6 can inhibit concentration expression of miR-145; VSMCs cells showed an increasing trend with time. Overexpression of circLRP6 can inhibit the proliferation process of VSMCs cells, The proliferation activity of cells was enhanced after circLRP6 knockout, and Overexpression of miR-145 could enhance the proliferation activity of VSMCs; Overexpression of circLRP6 could promote apoptosis process of VSMCs, while knockout of circLRP6 and Overexpression of miR-145 could inhibit apoptosis ability of VSMCs; Overexpression of circLRP6 can inhibit migration ability of VSMCs cells. Overexpression of circLRP6 after knockout and miR-145 can enhance the migration ability of cells; After circLRP6 overexpression in VSMCs, α-SMA, SM22α And expression concentration of Calponin protein increased, IL-1ß. The concentration and expression of MMP-2 and MMP-9 protein decreased After knockout of circLRP6 and Overexpression of miR-145, α-SMA, SM22α, And expression concentration of Calponin protein decreased, IL-1ß. The expression of MMP-2 and MMP-9 protein increased (P < .05). Conclusion: CircLRP6 is low expressed in intracranial aneurysms and negatively correlates with miR-145 expression. CircLRP6 may be involved in the development of intracranial aneurysms by influencing VSMC phenotype transformation. CircLRP6 acts as a natural sponge for miR-145, regulating VSMC proliferation, migration, and differentiation and promoting apoptosis, ultimately inhibiting the development of intracranial aneurysms. This study provides a theoretical basis for clinical research on the mechanism of intracranial aneurysms.

Application of the Willis Covered Stent in the Treatment of Complex Vascular Diseases of the Internal Carotid Artery and Vertebral Artery: A Retrospective Single-Center Experience.

Objective: To retrospectively evaluate the efficacy and security of Willis covered stent (WCS) deployment for complex vascular diseases of the internal carotid (ICA) and vertebral (VA) arteries. Methods: Retrospective analysis was performed on complex vascular disease patients (n=36) treated with WCSs at our center between March 2017 and December 2022, with a 3-36-months follow-up surveillance and digital subtraction angiography (DSA) examination. Results: The WCSs were successfully deployed in all the patients. The 36 included lesions were carotid-cavernous sinus fistulas (CCFs; n=10) (27.8%), complex saccular aneurysms (n=10) (27.8%), traumatic pseudoaneurysms (n=7) (19.4%), blood blister-like aneurysms (BBAs; n=5) (13.9%), and iatrogenic carotid or vertebral artery ruptures (n=4) (11.1%). The WCS was released at the communicating segment (n=2) (5.6%), the ophthalmic segment (n=3) (8.3%), the clinoid and cavernous segment (n=28) (77.8%), the petrous segment (n=2) (5.6%) of ICA and the V3 segment (n=1) (2.8%) of VA. Postoperative DSA showed complete lesion occlusion in 26 patients (72.2%) who were immediately treated with WCSs, and endoleaks occurred in 3 patients (8.3%) (endoleaks resolved postadjustment in 7 patients (19.4%)). In patients (n=3) (8.3%) treated with double stents at the break of the ICA, the endoleak remained in 1 CCF patient (2.8%) during the 3-month follow-up, and the residual shunt disappeared after the second stent system was placed 3 months later. No aneurysm, bleeding or infarct recurrence reported, and only 1 patient (2.8%) had mild asymptomatic in-stent stenosis. Deaths and procedural complications did not occur during follow-up. Conclusion: Treatment with a WCS for intracranial complex vascular diseases resulted in satisfactory clinical outcomes and appeared effective and safe. Controlled, multicenter, large sample sizes and longer follow-up periods studies are necessary.

Brain-Derived Extracellular Vesicles Induce Vasoconstriction and Reduce Cerebral Blood Flow in Mice.

Traumatic brain injury (TBI) impairs cerebrovascular autoregulation and reduces cerebral blood flow (CBF), leading to ischemic secondary injuries. We have shown that injured brains release brain-derived extracellular vesicles (BDEVs) into circulation, where they cause a systemic hypercoagulable state that rapidly turns into consumptive coagulopathy. The BDEVs induce endothelial injury and permeability, leading to the hypothesis that they contribute to TBI-induced cerebrovascular dysregulation. In a study designed to test this hypothesis, we detected circulating BDEVs in C57BL/6J mice subjected to severe TBI, reaching peak levels of 3 × 104/µL at 3 h post-injury (71.2 ± 21.5% of total annexin V-binding EVs). We further showed in an adaptive transfer model that 41.7 ± 5.8% of non-injured mice died within 6 h after being infused with 3 × 104/µL of BDEVs. The BDEVs transmigrated through the vessel walls, induced rapid vasoconstriction by inducing calcium influx in vascular smooth muscle cells, and reduced CBF by 93.8 ± 5.6% within 30 min after infusion. The CBF suppression was persistent in mice that eventually died, but it recovered quickly in surviving mice. It was prevented by the calcium channel blocker nimodipine. When being separated, neither protein nor phospholipid components from the lethal number of BDEVs induced vasoconstriction, reduced CBF, and caused death. These results demonstrate a novel vasoconstrictive activity of BDEVs that depends on the structure of BDEVs and contributes to TBI-induced disseminated cerebral ischemia and sudden death.

Risk Factors for Cerebral Infarction After Moderate or Severe Traumatic Brain Injury.

PURPOSE: Posttraumatic cerebral infarction (PTCI) is a common and relatively serious complication of traumatic brain injury (TBI) without a clear etiology. Evaluating risk factors in advance is particularly important to predict and avoid the occurrence of PTCI. PATIENTS AND METHODS: We retrospectively analyzed 297 patients with moderate to severe TBI admitted to the Department of Neurosurgery in our hospital from January 2019 to September 2020 and evaluated the effects of various factors such as age, sex, admission Glasgow Coma Scale (GCS), skull base fracture, subarachnoid hemorrhage (SAH), brain herniation, hypotensive shock, and decompressive craniectomy on the incidence of PTCI. We also performed a multivariate logistics regression analysis on the relevant factors identified and evaluated the diagnostic value of each risk factor in advance by receiver operating characteristic (ROC) analyses. RESULTS: Among the patients, 32 (10.77%) suffered PTCI. The incidence rates of PTCI in those with GCS scores of 3-8 and 9-12 were 15.87% (30/189) and 1.85% (2/108), respectively, while the rates were 18.84% (13/69), 15.03% (29/193), 18.57% (13/70), and 20.59% (14/68) in those with skull base fractures, traumatic SAH, brain herniation, and hypotensive shock, respectively, and 14.38% (23/160) in those who underwent decompressive craniectomy. These differences in PTCI incidence were statistically significant. However, the differences in PTCI incidence caused by patient age and sex were not statistically significant. CONCLUSION: Low GCS score, skull base fractures, traumatic SAH, brain herniation, hypotensive shock, and decompressive craniectomy are risk factors for the occurrence of PTCI, while age and sex are not significantly correlated with the occurrence of PTCI.

Conformation-dependent blockage of activated VWF improves outcomes of traumatic brain injury in mice.

Traumatic brain injury-induced coagulopathy (TBI-IC) causes life-threatening secondary intracranial bleeding. Its pathogenesis differs mechanistically from that of coagulopathy arising from extracranial injuries and hemorrhagic shock, but it remains poorly understood. We report results of a study designed to test the hypothesis that von Willebrand factor (VWF) released during acute TBI is intrinsically hyperadhesive because its platelet-binding A1-domain is exposed and contributes to TBI-induced vascular leakage and consumptive coagulopathy. This hyperadhesive VWF can be selectively blocked by a VWF A2-domain protein to prevent TBI-IC and to improve neurological function with a minimal risk of bleeding. We demonstrated that A2 given through intraperitoneal injection or IV infusion reduced TBI-induced death by >50% and significantly improved the neurological function of C57BL/6J male mice subjected to severe lateral fluid percussion injury. A2 protected the endothelium from extracellular vesicle-induced injury, reducing TBI-induced platelet activation and microvesiculation, and preventing a TBI-induced hypercoagulable state. A2 achieved this therapeutic efficacy by specifically blocking the A1 domain exposed on the hyperadhesive VWF released during acute TBI. These results suggest that VWF plays a causal role in the development of TBI-IC and is a therapeutic target for this life-threatening complication of TBI.

Placenta-derived extracellular vesicles induce preeclampsia in mouse models.

Preeclampsia is a pregnancy-induced condition that impairs the mother's health and results in pregnancy termination or premature delivery. Elevated levels of placenta-derived extracellular vesicles (pcEV) in the circulation have been consistently associated with preeclampsia, but whether these vesicles induce preeclampsia or are the product of preeclampsia is not known. Guided by a small cohort study of preeclamptic patients, we examined the impact of pcEV on the pathogenesis of preeclampsia in mouse models. We detected pcEV in pregnant C56BL/6J mice with a peak level of 3.8±0.9×107/mL at 17-18 days post-coitum. However, these pregnant mice developed hypertension and proteinuria only after being infused with vesicles purified from injured placenta. These extracellular vesicles released from injured placenta disrupted endothelial integrity and induced vasoconstriction. Enhancing the clearance of extracellular vesicles prevented the development of the extracellular vesicle-induced preeclampsia in mice. Our results demonstrate a causal role of pcEV in preeclampsia and identify microvesicle clearance as a new therapeutic strategy for the treatment of this pregnancy-associated complication.

Cognitive impairment after traumatic brain injury is associated with reduced long-term depression of excitatory postsynaptic potential in the rat hippocampal dentate gyrus.

Traumatic brain injury can cause loss of neuronal tissue, remote symptomatic epilepsy, and cognitive deficits. However, the mechanisms underlying the effects of traumatic brain injury are not yet clear. Hippocampal excitability is strongly correlated with cognitive dysfunction and remote symptomatic epilepsy. In this study, we examined the relationship between traumatic brain injury-induced neuronal loss and subsequent hippocampal regional excitability. We used hydraulic percussion to generate a rat model of traumatic brain injury. At 7 days after injury, the mean modified neurological severity score was 9.5, suggesting that the neurological function of the rats was remarkably impaired. Electrophysiology and immunocytochemical staining revealed increases in the slope of excitatory postsynaptic potentials and long-term depression (indicating weakened long-term inhibition), and the numbers of cholecystokinin and parvalbumin immunoreactive cells were clearly reduced in the rat hippocampal dentate gyrus. These results indicate that interneuronal loss and changes in excitability occurred in the hippocampal dentate gyrus. Thus, traumatic brain injury-induced loss of interneurons appears to be associated with reduced long-term depression in the hippocampal dentate gyrus.

von Willebrand factor enhances microvesicle-induced vascular leakage and coagulopathy in mice with traumatic brain injury.

von Willebrand factor (VWF) is an adhesive ligand, and its activity is proteolytically regulated by the metalloprotease ADAMTS-13 (a disintegrin and metalloprotease with thrombospondin type 1 repeat 13). An elevated level of plasma VWF has been widely considered a marker for endothelial cell activation in trauma and inflammation, but its causal role in these pathological conditions remains poorly defined. Using a fluid percussion injury mouse model, we demonstrated that VWF released during acute traumatic brain injury (TBI) was activated and became microvesicle-bound. The VWF-bound microvesicles promoted vascular leakage and systemic coagulation. Recombinant ADAMTS-13 given either before or after TBI reduced the VWF reactivity with minimal influence on VWF secretion. rADAMTS-13 protected the integrity of endothelial cell barriers and prevented TBI-induced coagulopathy by enhancing VWF cleavage without impairing basal hemostasis. Promoting microvesicle clearance by lactadherin had efficacy similar to that of rADAMTS-13. This study uncovers a novel synergistic action between VWF and cellular microvesicles in TBI-induced vascular leakage and coagulopathy and demonstrates protective effects of rADAMTS-13.

Endothelial colony-forming cell-derived exosomes restore blood-brain barrier continuity in mice subjected to traumatic brain injury.

Traumatic brain injury (TBI) tends to cause disruption of the blood-brain barrier (BBB). Previous studies have shown that intravenously or intracerebroventricularly infused human umbilical cord blood-derived endothelial colony-forming cells (ECFCs) can home to injury sites and improve outcomes in mice subjected to experimental TBI. Several reports have demonstrated that these cells did not incorporate directly into newly formed vasculature but instead stimulated the proliferation and migration of tissue-resident endothelial cells (ECs) via paracrine mechanisms. In the present study, exosomes, which range from 30 to 150 nm in diameter, were isolated from ECFC-conditioned medium. The exosomes were labeled with PKH67 ex vivo, and we observed that they were taken up by ECs with high efficiency after 12 h of incubation. Pretreatment with ECFC-derived exosomes promoted the migration of ECs subjected to scratch injury, and incubating ECs exposed to hypoxia with ECFC-derived exosomes decreased PTEN expression, stimulated AKT phosphorylation and increased tight junction (TJ) protein expression in the cells. Furthermore, in vivo delivery of ECFC-derived exosomes into TBI mice also inhibited PTEN expression and increased AKT expression, changes accompanied by reductions in Evans blue (EB) dye extravasation, brain edema and TJ degradation. These data demonstrated that ECFC-derived exosomes have beneficial effects on BBB integrity in mice with TBI.

Dexmedetomidine attenuates traumatic brain injury: action pathway and mechanisms.

Traumatic brain injury induces potent inflammatory responses that can exacerbate secondary blood-brain barrier (BBB) disruption, neuronal injury, and neurological dysfunction. Dexmedetomidine is a novel α2-adrenergic receptor agonist that exert protective effects in various central nervous system diseases. The present study was designed to investigate the neuroprotective action of dexmedetomidine in a mouse traumatic brain injury model, and to explore the possible mechanisms. Adult male C57BL/6J mice were subjected to controlled cortical impact. After injury, animals received 3 days of consecutive dexmedetomidine therapy (25 µg/kg per day). The modified neurological severity score was used to assess neurological deficits. The rotarod test was used to evaluate accurate motor coordination and balance. Immunofluorescence was used to determine expression of ionized calcium binding adapter molecule-1, myeloperoxidase, and zonula occluden-1 at the injury site. An enzyme linked immunosorbent assay was used to measure the concentration of interleukin-1ß (IL-1ß), tumor necrosis factor α, and IL-6. The dry-wet weight method was used to measure brain water content. The Evans blue dye extravasation assay was used to measure BBB disruption. Western blot assay was used to measure protein expression of nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3), caspase-1 p20, IL-1ß, nuclear factor kappa B (NF-κB) p65, occluding, and zonula occluden-1. Flow cytometry was used to measure cellular apoptosis. Results showed that dexmedetomidine treatment attenuated early neurological dysfunction and brain edema. Further, dexmedetomidine attenuated post-traumatic inflammation, up-regulated tight junction protein expression, and reduced secondary BBB damage and apoptosis. These protective effects were accompanied by down-regulation of the NF-κB and NLRP3 inflammasome pathways. These findings suggest that dexmedetomidine exhibits neuroprotective effects against acute (3 days) post-traumatic inflammatory responses, potentially via suppression of NF-κB and NLRP3 inflammasome activation.

Selective NLRP3 inflammasome inhibitor reduces neuroinflammation and improves long-term neurological outcomes in a murine model of traumatic brain injury.

The nucleotide-binding oligomerization domain (NOD)-like receptor family pyrin domain containing 3 (NLRP3) inflammasome-mediated inflammatory response has emerged as a prominent contributor to the pathophysiological processes of traumatic brain injury (TBI). Recently, a potent, selective, small-molecule NLRP3 inflammasome inhibitor, MCC950, was described. Here, we investigated the effect of MCC950 on inflammatory brain injury and long-term neurological outcomes in a mouse model of TBI. Male C57/BL6 mice were subjected to TBI using the controlled cortical impact injury (CCI) system. Western blotting, flow cytometry, and immunofluorescence assays were utilized to analyze post-traumatic NLRP3 inflammasome expression and determine its cellular source. We found that NLRP3 inflammasome expression was significantly increased in the peri-contusional cortex and that microglia were the primary source of this expression. The effects of MCC950 on mice with TBI were then determined using post-assessments including analyses of neurological deficits, brain water content, traumatic lesion volume, neuroinflammation, blood-brain barrier (BBB) integrity, and cell death. MCC950 treatment resulted in a better neurological outcome after TBI by alleviating brain edema, reducing lesion volume, and improving long-term motor and cognitive functions. The therapeutic window for MCC950 against TBI was as long as 6 h. Furthermore, the neuroprotective effect of MCC950 was associated with reduced microglial activation, leukocyte recruitment, and pro-inflammatory cytokine production. In addition, MCC950 preserved BBB integrity, alleviated TBI-induced loss of tight junction proteins, and attenuated cell death. Notably, the efficacy of MCC950 was abolished in microglia-depleted mice. These results indicate that microglia-derived NLRP3 inflammasome may be primarily involved in the inflammatory response to TBI, and specific NLRP3 inflammasome inhibition using MCC950 may be a promising therapeutic approach for patients with TBI.

Dexmedetomidine attenuated early brain injury in rats with subarachnoid haemorrhage by suppressing the inflammatory response: The TLR4/NF-κB pathway and the NLRP3 inflammasome may be involved in the mechanism.

Early brain injury (EBI) plays a pivotal role in the prognosis of patients with subarachnoid haemorrhage (SAH). Dexmedetomidine (DEX), a highly selective α2 receptor agonist, is reported to exert multiple protective effects in many neurological diseases. This study was designed to investigate whether DEX had neuroprotective functions in EBI after SAH, and to explore the possible mechanisms. The SAH model was established by an endovascular perforation in adult male Sprague-Dawley (SD) rats. DEX (25 µg/kg) or vehicle was administered intraperitoneally 2 h after SAH. Neurological deficits, brain oedema, inflammation, BBB damage, and cell apoptosis at 24 h after SAH were evaluated. Additionally, the expression of components of the Toll-like receptor 4 (TLR4)/nuclear factor-κB (NF-κB) pathway, and the nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome were also assessed. We demonstrated that DEX treatment improved neurological scores, alleviated brain oedema, reduced the permeability of the blood-brain barrier (BBB), and up-regulated the expression of tight junction proteins. DEX treatment could reduce the neutrophil infiltration, microglial activation, and pro-inflammatory factor release. In addition, DEX alleviated cell apoptosis at 24 h after SAH. Notably, DEX could also suppress the activation of the TLR4/NF-κB pathway and the NLRP3 inflammasome. These findings suggested that treatment with DEX after SAH attenuated SAH-induced EBI, partially through the suppression of the TLR4/NF-κB pathway and the NLRP3 inflammasome.

Anti-inflammatory and immunomodulatory mechanisms of atorvastatin in a murine model of traumatic brain injury.

BACKGROUND: Neuroinflammation is an important secondary injury mechanism that has dual beneficial and detrimental roles in the pathophysiology of traumatic brain injury (TBI). Compelling data indicate that statins, a group of lipid-lowering drugs, also have extensive immunomodulatory and anti-inflammatory properties. Among statins, atorvastatin has been demonstrated as a neuroprotective agent in experimental TBI; however, there is a lack of evidence regarding its effects on neuroinflammation during the acute phase of TBI. The current study aimed to evaluate the effects of atorvastatin therapy on modulating the immune reaction, and to explore the possible involvement of peripheral leukocyte invasion and microglia/macrophage polarization in the acute period post-TBI. METHODS: C57BL/6 mice were subjected to TBI using a controlled cortical impact (CCI) device. Either atorvastatin or vehicle saline was administered orally starting 1 h post-TBI for three consecutive days. Short-term neurological deficits were evaluated using the modified neurological severity score (mNSS) and Rota-rod. Brain-invading leukocyte subpopulations were analyzed by flow cytometry and immunohistochemistry. Pro- and anti-inflammatory cytokines and chemokines were examined using enzyme-linked immunosorbent assay (ELISA). Markers of classically activated (M1) and alternatively activated (M2) microglia/macrophages were then determined by quantitative real-time PCR (qRT-PCR) and flow cytometry. Neuronal apoptosis was identified by double staining of terminal deoxynucleotidyl transferase-dUTP nick end labeling (TUNEL) staining and immunofluorescence labeling for neuronal nuclei (NeuN). RESULTS: Acute treatment with atorvastatin at doses of 1 mg/kg/day significantly reduced neuronal apoptosis and improved behavioral deficits. Invasions of T cells, neutrophils and natural killer (NK) cells were attenuated profoundly after atorvastatin therapy, as was the production of pro-inflammatory cytokines (IFN-γ and IL-6) and chemokines (RANTES and IP-10). Notably, atorvastatin treatment significantly increased the proportion of regulatory T cells (Tregs) in both the peripheral spleen and brain, and at the same time, increased their main effector cytokines IL-10 and TGF-ß1. We also found that atorvastatin significantly attenuated total microglia/macrophage activation but augmented the M2/M1 ratio by both inhibiting M1 polarization and enhancing M2 polarization. CONCLUSIONS: Our data demonstrated that acute atorvastatin administration could modulate post-TBI neuroinflammation effectively, via a mechanism that involves altering peripheral leukocyte invasion and the alternative polarization of microglia/macrophages.

IL-2/Anti-IL-2 Complex Attenuates Inflammation and BBB Disruption in Mice Subjected to Traumatic Brain Injury.

Traumatic brain injury (TBI) induces the excessive inflammation and disruption of blood-brain barrier, both of which are partially mediated by the activation of microglia and release of inflammatory cytokines. Previous reports showed that administration of regulatory T cells (Tregs) could suppress inflammation and promote neurological function recovery, and that the IL-2/anti-IL-2 complex (IL-2C) could increase the number of Tregs. Thus, we hypothesized that IL-2C-mediated expansion of Tregs would be beneficial in mice subjected to TBI. In this study, mice received an intraperitoneal injection of IL-2C for three consecutive days. We observed that IL-2C dose-dependently increased Tregs without affecting the populations of CD4, CD8, or natural killer cells. IL-2C could improve the neurological recovery and reduce brain edema, tissue loss, neutrophils infiltration, and tight junction proteins degradation. Furthermore, this complex could also reduce the expression of CD16/32, IL-1ß, or TNF-α, and elevate the expression of CD206, arginase 1, or TGF-ß. These results suggest that IL-2C could be a potential therapeutic method to alleviate excessive inflammation and maintain blood vessel stability after TBI.

Methylprednisolone sodium succinate reduces BBB disruption and inflammation in a model mouse of intracranial haemorrhage.

Inflammation and disruption of the blood-brain barrier (BBB) cause oedema and secondary brain injury after intracranial haemorrhage (ICH), which is closely related to patient prognosis. Methylprednisolone sodium succinate (MPSS), a well-known immunosuppressive agent, is widely applied in many diseases to inhibit inflammation. In this study, we investigated the effect of MPSS on inflammation and disruption of the BBB in a model mouse of ICH. ICH was induced by injecting collagenase into the right striatum of male C57/BL mice. Permeability of BBB was measured with Evans Blue assay and brain oedema was detected by measurement of brain water content. Expressions of NF-κB, TLR4, occludin, ZO-1, IL-1ß, TNF-α, Bax, and Bcl-2 were determined by Western Blot. Neutrophils, microglia were measured by immunohistochemistry staining, neuronal apoptosis was measured by TUNEL and NeuN co-stained. Administration of MPSS post-ICH significantly reduced permeability of the BBB and brain oedema and upregulated expression of ZO-1 and Occludin. MPSS inhibited inflammatory responses, including reducing proinflammatory cytokines (IL-1ß, TNF-α), suppressing infiltration of neutrophils and activation of microglia. This was accompanied by attenuated activation of the TLR4/NF-κB signalling pathway. In addition, MPSS reduced neuronal apoptosis through increasing Bcl-2 expression and reducing Bax expression. MPSS suppressed inflammatory responses, attenuated disruption of the BBB and reduced neuronal apoptosis, contributing to reduction of secondary brain injury after ICH. These results suggest that MPSS may be a potential therapy for ICH.