Ultrasound combined with urokinase under key-shaped bone window enhances blood clot lysis in an in vitro model of spontaneous intracerebral hemorrhage.

OBJECTIVE: Minimally invasive surgery for spontaneous intracerebral hemorrhage is impeded by inadequate lysis of the target blood clot. Ultrasound is thought to expedite intravascular thrombolysis, thereby facilitating vascular recanalization. However, the impact of ultrasound on intracerebral blood clot lysis remains uncertain. This study aimed to explore the feasibility of combining ultrasound with urokinase to enhance blood clot lysis in an in vitro model of spontaneous intracerebral hemorrhage. METHODS: The blood clots were divided into four groups: control group, ultrasound group, urokinase group, and ultrasound + urokinase group. Using our experimental setup, which included a key-shaped bone window, we simulated a minimally invasive puncture and drainage procedure for spontaneous intracerebral hemorrhage. The blood clot was then irradiated using ultrasound. Blood clot lysis was assessed by weighing the blood clot before and after the experiment. Potential adverse effects were evaluated by measuring the temperature variation around the blood clot in the ultrasound + urokinase group. RESULTS: A total of 40 blood clots were observed, with 10 in each experimental group. The blood clot lysis rate in the ultrasound group, urokinase group, and ultrasound + urokinase group (24.83 ± 4.67%, 47.85 ± 7.09%, 61.13 ± 4.06%) was significantly higher than that in the control group (16.11 ± 3.42%) (p = 0.02, p < 0.001, p < 0.001). The blood clot lysis rate in the ultrasound + urokinase group (61.13 ± 4.06%) was significantly higher than that in the ultrasound group (24.83 ± 4.67%) (p < 0.001) or urokinase group (47.85 ± 7.09%) (p < 0.001). In the ultrasound + urokinase group, the mean increase in temperature around the blood clot was 0.26 ± 0.15°C, with a maximum increase of 0.38 ± 0.09°C. There was no significant difference in the increase in temperature regarding the main effect of time interval (F = 0.705, p = 0.620), the main effect of distance (F = 0.788, p = 0.563), or the multiplication interaction between time interval and distance (F = 1.100, p = 0.342). CONCLUSIONS: Our study provides evidence supporting the enhancement of blood clot lysis in an in vitro model of spontaneous intracerebral hemorrhage through the combined use of ultrasound and urokinase. Further animal experiments are necessary to validate the experimental methods and results.

Spontaneous brain activity in the hippocampal regions could characterize cognitive impairment in patients with Parkinson's disease.

OBJECTIVE: This study aimed to investigate whether spontaneous brain activity can be used as a prospective indicator to identify cognitive impairment in patients with Parkinson's disease (PD). METHODS: Resting-state functional magnetic resonance imaging (RS-fMRI) was performed on PD patients. The cognitive level of patients was assessed by the Montreal Cognitive Assessment (MoCA) scale. The fractional amplitude of low-frequency fluctuation (fALFF) was applied to measure the strength of spontaneous brain activity. Correlation analysis and between-group comparisons of fMRI data were conducted using Rest 1.8. By overlaying cognitively characterized brain regions and defining regions of interest (ROIs) based on their spatial distribution for subsequent cognitive stratification studies. RESULTS: A total of 58 PD patients were enrolled in this study. They were divided into three groups: normal cognition (NC) group (27 patients, average MoCA was 27.96), mild cognitive impairment (MCI) group (21 patients, average MoCA was 23.52), and severe cognitive impairment (SCI) group (10 patients, average MoCA was 17.3). It is noteworthy to mention that those within the SCI group exhibited the most advanced chronological age, with an average of 74.4 years, whereas the MCI group displayed a higher prevalence of male participants at 85.7%. It was found hippocampal regions were a stable representative brain region of cognition according to the correlation analysis between the fALFF of the whole brain and cognition, and the comparison of fALFF between different cognitive groups. The parahippocampal gyrus was the only region with statistically significant differences in fALFF among the three cognitive groups, and it was also the only brain region to identify MCI from NC, with an AUC of 0.673. The paracentral lobule, postcentral gyrus was the region that identified SCI from NC, with an AUC of 0.941. The midbrain, hippocampus, and parahippocampa gyrus was the region that identified SCI from MCI, with an AUC of 0.926. CONCLUSION: The parahippocampal gyrus was the potential brain region for recognizing cognitive impairment in PD, specifically for identifying MCI. Thus, the fALFF of parahippocampal gyrus is expected to contribute to future study as a multimodal fingerprint for early warning.

Deferoxamine reduces endothelial ferroptosis and protects cerebrovascular function after experimental traumatic brain injury.

Cerebrovascular dysfunction resulting from traumatic brain injury (TBI) significantly contributes to poor patient outcomes. Recent studies revealed the involvement of iron metabolism in neuronal survival, yet its effect on vasculature remains unclear. This study aims to explore the impact of endothelial ferroptosis on cerebrovascular function in TBI. A Controlled Cortical Impact (CCI) model was established in mice, resulting in a significant increase in iron-related proteins such as TfR1, FPN1, and FTH, as well as oxidative stress biomarker 4HNE. This was accompanied by a decline in expression of the ferroptosis inhibitor GPX4. Moreover, Perls' staining and nonhemin iron content assay showed iron overload in brain microvascular endothelial cells (BMECs) and the ipsilateral cortex. Immunofluorescence staining revealed more FTH-positive cerebral endothelial cells, consistent with impaired perfusion vessel density and cerebral blood flow. As a specific iron chelator, deferoxamine (DFO) treatment inhibited such ferroptotic proteins expression and the accumulation of lipid-reactive oxygen species following CCI, enhancing glutathione peroxidase (GPx) activity. DFO treatment significantly reduced iron deposition in BMECs and brain tissue, and increased density of the cerebral capillaries as well. Consequently, DFO treatment led to improvements in cerebral blood flow (as measured by laser speckle imaging) and behavioral performance (as measured by the neurological severity scores, rotarod test, and Morris water maze test). Taken together, our results indicated that TBI induces remarkable iron disorder and endothelial ferroptosis, and DFO treatment may help maintain iron homeostasis and protect vascular function. This may provide a novel therapeutic strategy to prevent cerebrovascular dysfunction following TBI.

Surgical treatment of traumatic frontal hematoma: comparison of the endoscopic supraorbital approach with frontotemporal approach.

Background: The objective of this study was to compare the efficacy, safety, and outcomes of the endoscopic supraorbital approach and frontotemporal approach for the treatment of traumatic frontal hematoma, with the aim of demonstrating the feasibility of the endoscopic supraorbital approach. Methods: A total of 24 cases underwent hematoma evacuation, including 10 cases using the endoscopic supraorbital approach and 14 cases using the frontotemporal approach. Baseline demographic data, hematoma clearance rate, blood loss, postoperative complications, and 6-month outcomes were retrospectively analyzed. Results: Both approaches effectively evacuated the hematoma, with hematoma clearance rates of 90.97 ± 10.23% in the endoscopic supraorbital group and 85.29 ± 16.15% in the frontotemporal approach group (p > 0.05). The supraorbital approach group demonstrated significantly shorter operation times compared to the frontotemporal approach group (116.50 ± 28.19 min vs. 193.29 ± 72.55 min, p < 0.05), as well as significantly less blood loss (55.00 ± 33.08 mL vs. 685.71 ± 840.20 mL, p < 0.05). There was no significant difference in the rate of postoperative complications between the two groups, and the majority of patients achieved favorable outcomes with a Glasgow Outcome Scale score of 4 or 5 in both groups. Conclusion: Compared to the frontotemporal approach, the endoscopic supraorbital approach offers advantages such as shorter operation times, reduced blood loss, similar treatment effects, and comparable complication rates. Therefore, the endoscopic supraorbital approach may serve as a viable alternative for the treatment of traumatic frontal hematoma.

Management of Primary Brainstem Hemorrhage: A Review of Outcome Prediction, Surgical Treatment, and Animal Model.

Primary brainstem hemorrhage (PBH) has the worst prognosis of all types of intracerebral hemorrhage. Currently, the management of PBH is controversial. Hematoma classification, scoring systems, and electrophysiological monitoring are critical for predicting the outcome of PBH. Surgery may be an effective treatment for PBH. Clinical studies have emphasized the importance of animal models for understanding the pathogenesis and pathological mechanisms of PBH. In this study, combined with recent studies, the outcome prediction, surgical treatment, and animal models of PBH were reviewed.

Ferritinophagy is Involved in Experimental Subarachnoid Hemorrhage-Induced Neuronal Ferroptosis.

Ferroptosis is a novel form of regulated cell death involved in the pathophysiological process of experimental subarachnoid hemorrhage (SAH), but how neuronal ferroptosis occurs remains unknown. In this study, we report that SAH-induced ferroptosis is macroautophagy/autophagy dependent because the inhibition of autophagy by knocking out autophagy-related gene 5 (ATG5) apparently mitigated SAH-induced ferroptosis. We created an experimental SAH model in Sprague-Dawley rats to determine the possible mechanism. We found that SAH can trigger neuronal ferroptosis, as evidenced by the disruption of iron homeostasis, elevation of intracellular lipid peroxidation (LPO) and decreased expression of ferroptosis-protective proteins. Then, we inhibited autophagy by ATG5 gene knockout, showing that autophagy inhibition can reduce the intracellular iron level and LPO, improve the expression of ferroptosis-protective proteins, and subsequently alleviate SAH-induced cell death. Additionally, autophagy inhibition also attenuated SAH prognostic indicators, such as brain edema, blood-brain barrier permeability, and neurological deficits. These findings not only present an opinion that SAH triggers neuronal ferroptosis via activation of ferritinophagy but also indicate that regulating ferritinophagy and maintaining iron homeostasis could provide clues for the prevention of early brain injury.

Pain and Psychological Distress: Effect of Microvascular Decompression on Sleep Disorders and Obsessions in Trigeminal Neuralgia.

Objective This study was aimed to investigate the effects of microvascular decompression (MVD) on sleep disorders and obsessions in trigeminal neuralgia. Methods Clinical data from 115 patients with trigeminal neuralgia treated with MVD from August 1, 2017 to May 31, 2018 at Jining First People's Hospital were analyzed retrospectively. The preoperative and postoperative risk factors for sleep disorders and obsessions, as well as the effects of MVD on sleep disorders and obsessions, were examined. Results In 115 patients, there were significant differences in preoperative sleep disorders associated with sex, monthly household income, pain in multiple branches, visual analog scale (VAS) score, and Self-Rating Depression Scale (SDS) score ( p < 0.05). Preoperative obsessions were significantly different according to age, gender, pain in multiple branches, monthly household income, VAS score, and Self-Rating Anxiety Scale (SAS) score groups ( p < 0.05). A 1-year recurrence was positively correlated with sleep disturbance (odds ratio = 3.829) and obsessions (odds ratio = 4.507). In addition, the results revealed a negative correlation between the manipulation of trigeminal neuralgia and postoperative sleep disorders ( B ≥ 1.043). Moreover, there was a significant difference in sleep disorders and obsessions before and 1 year after MVD ( p < 0.05). Conclusion For patients with trigeminal neuralgia, pain caused by sleep and obsession disorders should be examined early to identify an effective solution. Moreover, MVD, as a first treatment, is valuable for improving the physiological and psychological prognosis of patients.