ERBB1 alleviates secondary brain injury induced by experimental intracerebral hemorrhage in rats by modulating neuronal death via PLC-γ/PKC pathway.

AIMS: Intracerebral hemorrhage (ICH) is a disease with high rates of disability and mortality. The role of epidermal growth factor receptor 1 (ERBB1) in ICH was elucidated in this study. METHODS: ICH model was constructed by injecting autologous arterial blood into the right basal ganglia. The protein level of ERBB1 was detected by western blot analysis. To up- and downregulation of ERBB1 in rats, intraventricular injection of a lentivirus overexpression vector of ERBB1 and AG1478 (a specific inhibitor of ERBB1) was used. The cell apoptosis, neuronal loss, and pro-inflammatory cytokines were assessed by TUNEL, Nissl staining, and ELISA. Meanwhile, behavioral cognitive impairment of ICH rats was evaluated after ERBB1-targeted interventions. RESULTS: ERBB1 increased significantly in brain tissue of ICH rats. Overexpression of ERBB1 remarkably reduced cell apoptosis and neuronal loss induced by ICH, as well as pro-inflammatory cytokines and oxidative stress. Meanwhile, the behavioral and cognitive impairment of ICH rats were alleviated after upregulation of ERBB1; however, the secondary brain injury (SBI) was aggravated by AG1478 treatment. Furthermore, the upregulation of PLC-γ and PKC in ICH rats was reversed by AG1478 treatment. CONCLUSIONS: ERBB1 can improve SBI and has a neuroprotective effect in experimental ICH rats via PLC-γ/PKC pathway.

Multi-center application of a convolutional neural network for preoperative detection of cavernous sinus invasion in pituitary adenomas.

OBJECTIVE: Cavernous sinus invasion (CSI) plays a pivotal role in determining management in pituitary adenomas. The study aimed to develop a Convolutional Neural Network (CNN) model to diagnose CSI in multiple centers. METHODS: A total of 729 cases were retrospectively obtained in five medical centers with (n = 543) or without CSI (n = 186) from January 2011 to December 2021. The CNN model was trained using T1-enhanced MRI from two pituitary centers of excellence (n = 647). The other three municipal centers (n = 82) as the external testing set were imported to evaluate the model performance. The area-under-the-receiver-operating-characteristic-curve values (AUC-ROC) analyses were employed to evaluate predicted performance. Gradient-weighted class activation mapping (Grad-CAM) was used to determine models' regions of interest. RESULTS: The CNN model achieved high diagnostic accuracy (0.89) in identifying CSI in the external testing set, with an AUC-ROC value of 0.92 (95% CI, 0.88-0.97), better than CSI clinical predictor of diameter (AUC-ROC: 0.75), length (AUC-ROC: 0.80), and the three kinds of dichotomizations of the Knosp grading system (AUC-ROC: 0.70-0.82). In cases with Knosp grade 3A (n = 24, CSI rate, 0.35), the accuracy the model accounted for 0.78, with sensitivity and specificity values of 0.72 and 0.78, respectively. According to the Grad-CAM results, the views of the model were confirmed around the sellar region with CSI. CONCLUSIONS: The deep learning model is capable of accurately identifying CSI and satisfactorily able to localize CSI in multicenters.

Association Between Monocyte-to-Lymphocyte Ratio and Hematoma Progression After Cerebral Contusion.

BACKGROUND: The objective of this research was to examine the impact of the monocyte-to-lymphocyte ratio (MLR) on the advancement of hematoma after cerebral contusion. METHODS: The clinical information and laboratory test findings of people with cerebral contusion were retrospectively analyzed. Using the tertiles of MLR, the study participants were categorized into three groups, enabling the evaluation of the correlation between MLR and the advancement of hematoma after cerebral contusion. RESULTS: Among the cohort of patients showing progression, MLR levels were significantly higher compared with the nonprogress group (P < 0.001). The high MLR group had a significantly higher proportion of patients with hematoma progression compared with the medium and low MLR groups. However, the medium MLR group had a lower proportion of patients with hematoma progression compared with the low MLR group. High MLR levels were independently linked to a higher risk of hematoma progression (Odds Ratio 3.546, 95% Confidence Interval 1.187-10.597, P = 0.024). By incorporating factors such as Glasgow Coma Scale score on admission, anticoagulant/antiplatelet therapy, white blood cell count, and MLR into the model, the predictive performance of the model significantly improved (area under the curve 0.754). CONCLUSIONS: Our study suggests that MLR may serve as a potential indicator for predicting the progression of hematoma after cerebral contusion. Further research is necessary to investigate the underlying pathological and physiological mechanisms that contribute to the association between MLR and the progression of hematoma after cerebral contusion and to explore its clinical implications.

Caveolin-1 aggravates neurological deficits by activating neuroinflammation following experimental intracerebral hemorrhage in rats.

BACKGROUND: Intracerebral hemorrhage (ICH) is one of the stroke subtypes with the highest mortality. Secondary brain injury is associated with neurological dysfunction and poor prognosis after ICH. Caveolin-1 (CAV1) is the key protein of Caveolae. Previous studies have shown that CAV1 plays an important role in central nervous system diseases, and pointed out that in a collagenase-induced ICH model in vivo, CAV1 is associated with neuroinflammatory activation and poor neurological prognosis. In this study, we explore the role and the molecular mechanism of CAV1 in brain injury via a rat autologous whole blood injection model and an in vitro model of ICH. METHODS: Adult male Sprague-Dawley rats ICH model was induced through autologous whole blood injecting into the right basal ganglia. The changes in protein levels of CAV1 in brain tissues of ICH rats were detected by western blot analysis. The immunofluorescent staining was used to explore the changes of CAV1 in microglia/macrophages (Iba1+ cells). Lentivirus vectors were administered by intracerebroventricular injection to induce CAV1 overexpression and knockdown respectively. The western blot analysis, immunofluorescence staining, enzyme-linked immunosorbent assay, terminal deoxynucleotidyl transferase dUTP nick end labeling and Nissl staining were performed to explore the role of CAV1 in secondary brain injury after ICH. Meanwhile, the rotarod test, foot fault test, adhesive-removal test, and Modified Garcia Test, as well as Morris Water Maze test, were performed to evaluate the behavioral cognitive impairment of ICH rats after genetic intervention. Additionally, BV-2 cells treated with oxygen hemoglobin for 24 h, were used as an in vitro model of ICH in this study to explore the molecular mechanism of CAV1 in brain injury; we performed western blot analysis after precise regulation of CAV1 in BV2 cells to observe changes in protein levels and phosphorylated levels of C-Src, IKK-ß, and NF-κB. RESULTS: The expression of CAV1 in microglia/macrophages (Iba1+ cells) was elevated and reached the peak at 24 h after ICH. CAV1 knockdown ameliorated ICH-induced neurological deficits, while CAV1 overexpression significantly worsened neurological dysfunction of ICH rats. CAV1 knockdown attenuated cellular apoptosis and promoted neuronal survival in brain tissues of ICH rats, while the ICH rats with CAV1 overexpression presented more cellular apoptosis and neuronal loss. Meanwhile, CAV1 knockdown inhibited the microglia activation and neuroinflammatory response, while CAV1 overexpression abolished these effects and aggravated neuroinflammation in brain tissues of ICH rats. Additionally, by inducing to CAV1 knockdown in BV2 cells in an in vitro model of ICH, the levels of p-C-Src, CAV-1, p-CAV-1, and p-IKK-ß in cytoplasm and the level of NF-κB p65 in nucleus of BV2 cells were significantly decreased, while they were increased by inducing to CAV1 overexpression. CONCLUSIONS: Our research revealed CAV1 aggravated neurological dysfunction in a rat ICH model. CAV1 knockdown exerted neuroprotective effect by suppressing microglia activation and neuroinflammation after ICH might via the C-Src/CAV1/IKK-ß/NF-κB signaling pathway.

Time and Influencing Factors to Chronic Subdural Hematoma Resolution After Middle Meningeal Artery Embolization.

OBJECTIVE: We sought to describe the resolution time of chronic subdural hematoma (CSDH) after middle meningeal artery embolization (MMAE) and potential variables that may affect hematoma resolution. METHODS: A retrospective analysis was performed on CSDH patients between December 2018 and December 2021. Patient characteristics, radiologic manifestations, and data of hematoma resolution were recorded. Univariate and multivariate analyses were conducted to identify predictors of CSDH resolution time. RESULTS: A total of 53 patients were enrolled including 53 hematomas. Only 1 participant relapsed and did not require surgical evacuation. Hematoma resolution was observed in 27 (50.9%) at 4 months and 48 (90.6%) cases at the last radiologic follow-up. The median MMAE-to-resolution time was 19 weeks (interquartile range: 8-24). The burr-hole irrigation + MMAE group showed faster hematoma resolution than MMAE alone during early follow-up periods, but no significant difference was found at 6 months. Increased thickness of residual hematoma, excessive postoperative midline shift, high-density hematoma, mixed-density hematoma, separated hematoma, and anticoagulant or antiplatelet agents used were predictive of nonresolution at 4 months as determined by univariate analysis, whereas anticoagulant or antiplatelet agents used and high-density hematoma were not significant on multivariate analysis. No significant association was noted between hematoma resolution and comorbidities or other hematoma radiologic features. CONCLUSIONS: MMAE is an effective and minimally invasive treatment for CSDH with a lower recurrence rate. The median resolution time of CSDH following MMAE was 19 weeks (interquartile range: 8-24). Burr-hole irrigation contributed to early hematoma resolution but had no significant effect at 6 months. In addition, residual hematoma thickness, postoperative midline shift, and specific type of hematoma were associated with delayed hematoma resolution at 4 months.

Receptor-interacting protein 3-phosphorylated Ca2+ /calmodulin-dependent protein kinase II and mixed lineage kinase domain-like protein mediate intracerebral hemorrhage-induced neuronal necroptosis.

Necroptosis-mediated cell death is an important mechanism in intracerebral hemorrhage (ICH)-induced secondary brain injury (SBI). Our previous study has demonstrated that receptor-interacting protein 1 (RIP1) mediated necroptosis in SBI after ICH. However, further mechanisms, such as the roles of receptor-interacting protein 3 (RIP3), mixed lineage kinase domain-like protein (MLKL), and Ca2+ /calmodulin-dependent protein kinase II (CaMK II), remain unclear. We hypothesized that RIP3, MLKL, and CaMK II might participate in necroptosis after ICH, including their phosphorylation. The ICH model was induced by autologous blood injection. First, we found the activation of necroptosis after ICH in brain tissues surrounding the hematoma (propidium iodide staining). Meanwhile, the phosphorylation and expression of RIP3, MLKL, and CaMK II were differently up-regulated (western blotting and immunofluorescent staining). The specific inhibitors could suppress RIP3, MLKL, and CaMK II (GSK'872 for RIP3, necrosulfonamide for MLKL, and KN-93 for CaMK II). We found the necroptosis surrounding the hematoma and the concrete interactions in RIP3-MLKL/RIP3-CaMK II also both decreased after the specific intervention (co-immunoprecipitation). Then we conducted the short-/long-term neurobehavioral tests, and the rats with specific inhibition mostly had better performance. We also found less blood-brain barrier (BBB) injury, and less neuron loss (Nissl staining) in intervention groups, which supported the neurobehavioral tests. Besides, oxidative stress and inflammation were also alleviated with intervention, which had significant less reactive oxygen species (ROS), tumor necrosis factor (TNF)-α, lactate dehydrogenase (LDH), Iba1, and GFAP surrounding the hematoma. These results confirmed that RIP3-phosphorylated MLKL and CaMK II participate in ICH-induced necroptosis and could provide potential targets for the treatment of ICH patients.

Gut microbiota and its metabolites in non-small cell lung cancer and brain metastasis: from alteration to potential microbial markers and drug targets.

Background: The elevated mortality rate associated with non-small-cell lung cancer (NSCLC) is a well-established global concern. Considerable attention has been directed toward exploring the association between gut microbiota and various malignant tumors. We herein investigated the associations between the intestinal microbiome and its metabolites, particularly short-chain fatty acids (SCFAs), in patients with NSCLC at different stages, including early and brain metastasis (BM) stages. The findings aim to offer a fresh perspective on the diagnosis and management of NSCLC. Methods: Fecal samples were collected from 115 participants, comprising healthy controls (n = 35) and patients with treatment-naive NSCLC at the early stage (ELC, n = 40) and the BM stage (n = 40). Characterization of the intestinal microbiome and fecal SCFA levels was performed using 16S rRNA gene sequencing and gas chromatography. Results: The microbial diversity in patients with NSCLC was found to be less abundant and uniform, particularly in the BM stage. Significant alterations in the community structure of the gut microbiota were observed in patients with NSCLC, with an increase in pathogens in Fusobacteria and Proteobacteria and a decrease in SCFA-producing bacteria in Firmicutes and Actinobacteria, particularly in the BM stage. Meanwhile, microbial communities displayed intricate associations in patients with NSCLC. A biomarker panel (Faecalibacterium, Bifidobacterium, Butyricicoccus, Klebsiella, Streptococcus, and Blautia) successfully distinguished patients in the ELC and BM stages from healthy controls (area under the curve: 0.884). The overall concentration of fecal SCFAs was significantly lower in patients with BM compared to patients with ELC and healthy controls. Subgroup analysis of acetate and butyrate yielded similar results. Moreover, multiple disrupted pathways in the NSCLC group were identified using the Kyoto Encyclopedia of Genes and Genomes annotation, including lipid metabolism and genetic information processing, specifically in the BM stage. Conclusion: Compared with healthy controls, distinct host-microbe interactions were evident in different phases of patients with NSCLC. Furthermore, specific forms of the gut microbiome and SCFAs may serve as valuable biomarkers and therapeutic targets in the diagnosis and treatment of NSCLC.

Sensitive SERS detection of oral squamous cell carcinoma-related miRNAs in saliva via a gold nanohexagon array coupled with hybridization chain reaction amplification.

In this work, a highly specific and sensitive method for the detection of dual miRNAs was successfully developed by a hybridization chain reaction (HCR) amplification coupled with surface-enhanced Raman scattering (SERS) on Au-Ag hollow nanoparticles (Au-Ag HNPs) and a gold nanohexagon (AuNH) array. Two Raman reporter-labelled and hairpin DNA-modified Au-Ag HNPs acted as SERS probes (Au-Ag HNPs@4-MBA@HP1-1, Au-Ag HNPs@4-MBA@HP2-1, Au-Ag HNPs@DTNB@HP1-2, and Au-Ag HNPs@DTNB@HP2-2), and the hairpin DNA-modified AuNH array acted as the capture substrate. The HCR process could be triggered by the presence of target miRNAs, and long DNA hybridization chains on the substrate were formed by self-assembly rapidly, causing significant signal enhancement. Using the mentioned strategy, a low detection limit (LOD) of 6.51 aM for miR-31 and 6.52 aM for miR-21 in human saliva were obtained, showing the biosensor's remarkable sensitivity. The proposed biosensor also displays a significant specificity in detecting target miRNAs by introducing different interfering factors. This method has been successfully applied to detect and identify miR-21 and miR-31 in saliva from oral squamous cell carcinoma (OSCC) patients and healthy subjects. The results were consistent with those of the traditional test method in detecting target miRNAs, which confirmed the good accuracy of our method. Hence, the new assay method has great potential to be a valuable platform for detecting miRNAs in the early diagnosis of OSCC.

TREM2 modulates neuroinflammation with elevated IRAK3 expression and plays a neuroprotective role after experimental SAH in rats.

BACKGROUND: The modulation of neuroinflammation is a new direction that may alleviate the early brain injury after subarachnoid hemorrhage (SAH). Brain resident microglia/macrophages (Mi/MΦ) are the key drivers of neuroinflammation. Triggering receptor expressed on myeloid cells 2 (TREM2) has been reported to play a neuroprotective role by activating phagocytosis and suspending inflammatory response in experimental ischemic stroke and intracerebral hemorrhage. This study was designed to investigate the role of TREM2 on neuroinflammation and neuroprotective effects in a rat SAH model. METHODS: Adult male Sprague-Dawley rats were induced SAH through endovascular perforation. Lentivirus vectors were administered by i.c.v. to induce TREM2 overexpression or knockdown 7 days before SAH induction. Short- and long-term neurobehavioral tests, western blotting, immunofluorescence, enzyme-linked immunosorbent assay, terminal deoxynucleotidyl transferase dUTP nick end labeling and Nissl staining were performed to explore the neuroprotective role of TREM2 after SAH. RESULTS: The expression of TREM2 elevated in a rat SAH model with a peak at 48 h after SAH and mainly expressed in Mi/MΦ in brain. TREM2 overexpression improved short- and long-term neurological deficits induced by SAH in rats, while TREM2 knockdown worsened neurological dysfunction. The rats with TREM2 overexpressed presented less neuronal apoptosis and more neuronal survival at 48 h after SAH, while the rats with TREM2 knockdown presented on the contrary. TREM2 overexpression manifested activated phagocytosis and suppressed inflammatory response, with the increase of CD206+/CD11b+ cells and IL-10 expression as well as the decrease of the infiltration of MPO+ cells and the expression of TNF-α, IL-1ß. While TREM2 knockdown abolished these effects. The protein level of IRAK3, a negative regulatory factor of inflammation, was significantly elevated after TREM2 overexpression and declined after TREM2 knockdown. CONCLUSIONS: Our research suggested TREM2 played a neuroprotective role and improved the short- and long-term neurological deficits by modulating neuroinflammation after SAH. The modulation on neuroinflammation of TREM2 after SAH was related with the elevated protein level of IRAK3.

Apelin-13 attenuates early brain injury through inhibiting inflammation and apoptosis in rats after experimental subarachnoid hemorrhage.

BACKGROUND: Early brain injury (EBI) has been considered as the major contributor to the neurological dysfunction and poor clinical outcomes of subarachnoid hemorrhage (SAH). Studies showed that apelin-13 exhibits a neuroprotective effect in brain damage induced by cerebral ischemia. However, it remains unclear whether apelin-13 could exhibit the protective functions following SAH. The present study aimed to validate the neuroprotective role of apelin-13 in SAH, and further investigated the underlying mechanisms. METHODS AND RESULTS: We constructed SAH rat model and we found that apelin-13 significantly alleviated neurological disorder and brain edema, improved memory deficits in SAH rats. Apelin-13 treatment decreased contents of TNF-α and IL-1ß in cerebral spinal fluid of SAH rat by using ELISA. Apelin-13 treatment promoted the expression of APJ and Bcl-2, and decreased the level of active caspase-3 and Bax in the temporal cortex after SAH by using western blot. Also, apelin-13 attenuated the cortical cell death and neuronal degeneration as shown by TUNEL, FJB and Nissl staining. However, ML221, an inhibitor of APJ, significantly reversed all the above neuroprotective effects of apelin-13. Moreover, a neuron-microglia co-culture system, which mimic SAH in vitro, confirmed the protective effect of apelin-13 on neurons and the inhibitory effect on inflammation through apoptosis-related proteins. CONCLUSIONS: These data demonstrated that apelin-13 exhibit a neuroprotective role after SAH through inhibition of apoptosis in an APJ dependent manner.

BMAL1 attenuates intracerebral hemorrhage-induced secondary brain injury in rats by regulating the Nrf2 signaling pathway.

BACKGROUND: Intracerebral hemorrhage (ICH) is a severe cerebrovascular disease with high morbidity and mortality rates. Oxidative stress and inflammation are important pathological mechanisms of secondary brain injury (SBI) after ICH. Brain and muscle Arnt-like protein 1 (BMAL1), which forms the core component of the circadian clock, was previously shown to be involved in many diseases and to participate in oxidative stress and inflammatory responses. However, the role of BMAL1 in SBI following ICH is unknown. In addition, treatments targeting miR-155 and its downstream signaling pathway may exert a beneficial effect on SBI after ICH, while miR-155 may regulate Bmal1 mRNA stability and translation. Nevertheless, researchers have not clearly determined whetheantagomir-155 upregulates BMAL1 expression and subsequently attenuates ICH-induced brain injury in rats. METHODS: After establishing an ICH rat model by injecting autologous blood, the time course of changes in levels of the BMAL1 protein after ICH was analyzed. Subsequently, this study was designed to investigate the potential role and mechanisms of BMAL1 in SBI following ICH using lentiviral overexpression and antagomir-155 treatments. RESULTS: BMAL1 protein levels were significantly decreased in the ICH group compared to the sham group. Genetic overexpression of BMAL1 alleviated oxidative stress, inflammation, brain edema, blood-brain barrier injury, neuronal death, and neurological dysfunction induced by ICH. On the other hand, we observed that inhibiting miRNA-155 using antagomir-155 promoted the expression of BMAL1 and further activated the nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway to attenuate brain injury after ICH. CONCLUSIONS: These results reveal that BMAL1 serves as a neuroprotective agent in ICH and upregulation of BMAL1 attenuates ICH-induced SBI. Therefore, BMAL1 may be a promising therapeutic target for SBI following ICH.

A narrative review of adjuvant therapy for glioma: hyperbaric oxygen therapy.

Glioma is a kind of common malignant tumor in neurosurgery and has a high mortality and morbidity rate, which poses a serious threat to the health of people all over the world. Surgery is the preferred treatment for patients with glioma, radiotherapy or chemotherapy can be used after surgery. Although there are clear therapeutic protocols, the efficacy and safety of these protocols are clinically proven, a large number of patients are still dissatisfied with the treatment and the health of the patient remains unsatisfactory. Therefore, it is crucial to look for other treatments or complementary treatments. In the modern medical treatment, hyperbaric oxygen (HBO) therapy is widely used in various kinds of pathological state of adjuvant therapy, and existing studies confirm the efficacy of HBO therapy in combination with surgery, radiotherapy, chemotherapy, and photodynamic therapy. Studies have shown that HBO can inhibit the growth of tumor tissue as an adjunctive therapy. This provides novel insights into the clinical treatment of glioma patients. Although HBO is not licensed for use in cancer treatment, as a kind of adjuvant therapy, the treatment effect of HBO can be accepted by the patients and its cost lower, which could be regarded as an ideal safe treatment.

Atorvastatin ameliorates early brain injury through inhibition of apoptosis and ER stress in a rat model of subarachnoid hemorrhage.

Aneurysmal subarachnoid hemorrhage (SAH) is a severe cerebrovascular disease with very poor prognosis. The aim of the present study was to evaluate the protective effects of atorvastatin on early brain injury (EBI) after SAH using a perforation SAH model. Male Sprague-Dawley rats were randomly divided into four groups: the sham group, the SAH group (model group), SAH + 10 mg.kg-1day-1 atorvastatin (low atorvastatin group), and SAH + 20 mg.kg-1day-1 atorvastatin (high atorvastatin group). Atorvastatin was administered orally by gastric gavage for 15 days before operation. At 24 h after SAH, we evaluated the effects of atorvastatin on brain water content, apoptosis by TUNEL assay and scanning electron microscope (SEM), and the expression of apoptosis-related proteins by immunofluorescence and Western blotting analysis. Compared with the sham group, we observed increased brain water content, significant apoptosis, and elevated levels of apoptosis-related proteins including caspase-3, CCAAT enhancer-binding protein homologous protein (CHOP), the 78-kDa glucose-regulated protein (GRP78), and aquaporin-4 (AQP4) in the SAH group. Atorvastatin administration under all doses could significantly reduce brain water content, apoptosis, and the expression levels of caspase-3, CHOP, GRP78, and AQP4 at 24 h after SAH. Our data show that early treatment with atorvastatin effectively ameliorates EBI after SAH through anti-apoptotic effects and the effects might be associated inhibition of caspase-3 and endoplasmic reticulum (ER) stress related proteins CHOP and GRP78.

Fibrinolytic Therapy Improves Outcomes in Patients with Epidural Hematomas Following Cranioplasty: A Pilot Study.

BACKGROUND AND STUDY AIMS: Cranioplasty is a cosmetic procedure utilized to reconstruct cranial defects in patients following decompressive craniectomy. Epidural hematomas are a common complication of cranioplasty and often require surgical drainage. However, repeated surgery compromises patient safety and delays recovery. MATERIAL AND METHODS: We investigated the development of epidural hematomas among 131 patients who underwent cranioplasty. Then we explored the efficacy of urokinase (UK) injection for the noninvasive treatment of epidural hematomas. We observed that 15 patients presented with epidural hematoma following cranioplasty. UK (30,000 IU/3 mL) was injected into the hematoma cavity twice every 12 hours in the first postoperative day. Next we closed the subgaleal drain for 1.5 hours and connected it with a negative-pressure ball on full vacuum to allow drainage. Binary logistic regression analysis was used to evaluate the risk factors associated with the development of epidural hematomas. RESULTS: Our findings demonstrated that a sunken skin flap was a risk factor for epidural hematoma formation (p = 0.006). The decrease in epidural hematoma volume was 35.27 ± 7.27 mL in the first 12 hours on postoperative day 1 after UK treatment. All treated patients whose Glasgow Coma Scale score did not significantly change despite the epidural hematoma had an uneventful recovery without additional complications and were discharged from the hospital, except for one patient. CONCLUSION: Fibrinolytic therapy can be considered an optional treatment for postoperative epidural hematoma associated with cranioplasty, especially in patients who refused further operative treatment or who are not optimal candidates for a second surgery.