Hematoma Clearance Research Articles

Comparison of the Efficacy of Subosseous Window Neuro-Endoscopy and Minimally Invasive Craniotomy in the Treatment of Basal Ganglia Hypertensive Intracerebral Hemorrhage.

To compare the perioperative indexes and long-term effects of craniotomy and neuro-endoscopic hematoma removal in patients with hypertensive intracerebral hemorrhage (HICH) in the basal ganglia region. This study involved 128 patients with HICH in the basal ganglia region who were admitted to our hospital from February 2020 to June 2022. They were divided into 2 groups according to the random number table method. The craniotomy group (n = 70) underwent microsurgery with small bone window craniotomy with a side cleft, and the neuro-endoscopy group (n = 58) underwent small bone window neuro-endoscopic surgery. A 3-dimensional Slicer was used to calculate the hematoma volume and clearance rate and the postoperative brain tissue edema volume. The operation time, intraoperative blood loss, postoperative intracranial pressure, complications, mortality, and improvement in the modified Rankin scale score at 6 months postoperatively were compared between the two groups. The clearance rate was significantly higher in the neuro-endoscopy group than in the craniotomy group (94.16% ± 1.86% versus 90.87% ± 1.89%, P < 0.0001). The operation time was significantly lower in the neuro-endoscopy group than in the craniotomy group (89.9 ± 11.7 versus 203.7 ± 57.6min, P < 0.0001). Intraoperative blood loss was significantly higher in the craniotomy group (248.31 ± 94.65 versus 78.66 ± 28.96mL, P < 0.0001). The postoperative length of stay in the intensive care unit was 12.6 days in the neuro-endoscopy group and 14.0 days in the craniotomy group with no significant difference ( P = 0.196). Intracranial pressure monitoring showed no significant difference between the two groups on postoperative days 1 and 7. Intracranial pressure was significantly higher in the craniotomy group than in the neuro-endoscopy group on postoperative day 3 (15.1 ± 6.8 versus 12.5 ± 6.8mm Hg, P = 0.029). There was no significant difference in the mortality or outcome rate at 6 months postoperatively between the two groups. In patients with HICH in the basal ganglia region, neuro-endoscopy can significantly improve the hematoma clearance rate, reduce intraoperative hemorrhage and postoperative cerebral tissue edema, and improve surgical efficiency. However, the long-term prognosis of patients who undergo craniotomy through the lateral fissure is similar to that of patients who undergo neuro-endoscopic surgery.

Clinical application of 3DSlicer and Sina in minimally invasive puncture drainage of elderly patients with spontaneous intracerebral hemorrhage under local anesthesia

BackgroundDecreased organ function and poor physical compensatory capacity in elderly patients diagnosed with spontaneous intracerebral hemorrhage (ICH) can make surgical treatment procedures challenging and risky. Minimally invasive puncture drainage (MIPD) combined with urokinase infusion therapy is a safe and feasible method of treating ICH. This study aimed to compare the treatment efficacy of MIPD conducted under local anesthesia using either 3DSlicer + Sina application or computer tomography (CT)–guided stereotactic localization of hematomas in elderly patients diagnosed with ICH. MethodsThe study sample included 78 elderly patients (≥ 65 years of age) diagnosed with ICH for the first time. All patients exhibited stable vital signs and underwent surgical treatment. The study sample was randomly divided into two groups, either receiving 3DSlicer+Sina or CT-guided stereotactic assistance. The preoperative preparation time; hematoma localization accuracy rate; satisfactory hematoma puncture rate; hematoma clearance rate; postoperative rebleeding rate; Glasgow Coma Scale (GCS) score after 7 days; and modified Rankin scale (mRS) score 6 months after surgery were compared between the two groups. ResultsNo significant differences in gender, age, preoperative GCS score, preoperative hematoma volume (HV), and surgical duration were observed between the two groups (all p-values > 0.05). However, the preoperative preparation time was shorter in the group receiving 3DSlicer + Sina assistance compared to that receiving CT-guided stereotactic assistance (p-value < 0.001). Both groups exhibited significant improvement in GCS scores and reduction in HV after surgery (all p-values < 0.001). The accuracy of hematoma localization and puncture was 100% in both groups. There were no significant differences in surgical duration, postoperative hematoma clearance rate, rebleeding rate, postoperative GCS and mRS scores between the two groups (all p-values > 0.05). ConclusionsA combination of 3DSlicer and Sina is effective in accurately identifying hematomas in elderly patients with ICH exhibiting stable vital signs, thus simplifying MIPD surgeries conducted under local anesthesia. This procedure may also be preferred over CT-guided stereotactic localization in clinical practice due to its ease of use and accuracy in hematoma localization.

The efficacy of stereotactic minimally invasive thrombolysis at different catheter positions in the treatment of small- and medium-volume basal ganglia hemorrhage (SMITDCP I): a randomized, controlled, and blinded endpoint phase 1 trial.

The aim of this study was to evaluate the effects of stereotactic minimally invasive puncture with different catheter placement positions when combined with urokinase thrombolysis for the treatment of small- and medium-volume basal ganglia hemorrhage. Our goal was to identify the best minimally invasive catheter placement position to enhance therapeutic efficacy for patients with cerebral hemorrhage. The stereotactic minimally invasive thrombolysis at different catheter positions in the treatment of small- and medium-volume basal ganglia hemorrhage (SMITDCPI) was a randomized, controlled, and endpoint phase 1 trial. We recruited patients with spontaneous ganglia hemorrhage (medium-to-small and medium volume) who were treated in our hospital. All patients received stereotactic, minimally invasive punctures combined with an intracavitary thrombolytic injection of urokinase hematoma. A randomized number table method was used to divide the patients into two groups concerning the location of catheterization: a penetrating hematoma long-axis group and a hematoma center group. The general conditions of the two groups of patients were compared, and the data were analyzed, including the time of catheterization, the dosage of urokinase, the amount of residual hematoma, the hematoma clearance rate, complications, and the National Institute of Health stroke scale (NIHSS) score data at 1 month after surgery. Between June 2019 and March 2022, 83 patients were randomly recruited and assigned to the two groups as follows: 42 cases (50.60%) to the penetrating hematoma long-axis group and 41 cases (49.40%) to the hematoma center group. Compared with the hematoma center group, the long-axis group was associated with a significantly shorter catheterization time, a lower urokinase dose, a lower residual hematoma volume, a higher hematoma clearance rate, and fewer complications (P < 0.05). However, there were no significant differences between the two groups in terms of the NIHSS scores when tested 1 month after surgery (P > 0.05). Stereotactic minimally invasive puncture combined with urokinase for the treatment of small- and medium-volume hemorrhage in the basal ganglia, including catheterization through the long axis of the hematoma, led to significantly better drainage effects and fewer complications. However, there was no significant difference in short-term NIHSS scores between the two types of catheterization.

Enhanced liver X receptor signalling reduces brain injury and promotes tissue regeneration following experimental intracerebral haemorrhage: roles of microglia/macrophages

BackgroundInflammation-exacerbated secondary brain injury and limited tissue regeneration are barriers to favourable prognosis after intracerebral haemorrhage (ICH). As a regulator of inflammation and lipid metabolism, Liver X receptor (LXR) has...

Optimizing The Timing of Stereotactic Minimally Invasive Drainage for Hypertensive Intracerebral Hemorrhage

Intracerebral hemorrhage is a high-risk pathological event that is associated with formidable morality rates. Here, our objective was to perform a retrospective study to determine the best timing for drainage using physiological data on patients who received drainage at different timings. In this retrospective study, we reviewed 198 patients with hypertensive cerebral hemorrhage who underwent stereotactic drainage at the conventional timing (surgery within 12h of admission; control group) and 216 patients who underwent stereotactic drainage at a customized surgical timing (elective group). Follow-ups were performed at 3 and 6 months after surgery. The clinical indicators, including prognosis, hematoma clearance, recurrent hemorrhage, intracerebral infection, pulmonary infection, deep venous thrombosis, gastrointestinal hemorrhage, National Institutes of Health Stroke Scale scores, and matrix metallopeptidase 2 and 9 levels, were compared between the control and elective groups. Our data indicated that the elective group had significantly better prognosis compared to the control group (p = 0.021), with a higher rate of hematoma clearance (p = 0.004) and a lower rate of recurrent hemorrhage (p = 0.018). The total occurrence rate of post-surgery complications was also lower for the elective group (p = 0.026). NIHSS scores and serum MMP2/9 levels of the elective group were lower than those of the control group. Customized timing of stereotactic drainage may be superior to conventional fixed timing (within 12h post-hemorrhage) in reducing post-surgery complications and promoting recovery, which supports the potential use of customized timing of stereotactic minimally invasive drainage as a new convention in clinics.

Outcomes of Combined Endoscopic Surgery and Fibrinolytic Treatment Protocol for Intraventricular Hemorrhage: A Randomized Controlled Trial.

Intraventricular fibrinolysis (IVF) and endoscopic surgery (ES) are the new promising treatment strategies to enhance the rate of hematoma clearance, which might improve functional outcome. This study investigated and compared the outcomes among these interventions. A randomized (1:1) double-blinded trial was carried out between August 2018 and December 2021. The intervention and control groups comprised patients receiving IVF and/or ES and external ventricular drainage (EVD), respectively. All participants had experienced primary or secondary intraventricular hemorrhage (IVH) from spontaneous intracerebral hemorrhage with obstructive hydrocephalus complications. The primary outcome was modified Rankin Scale score 180 days post treatment. Interim assessments were planned for every 50 participants enrolled to ensure safety and efficacy. After enrollment of 110 participants (55 participants in each group), there was a difference in 30-day mortality (2 [3.6%] vs. 13 [32.7%] in the EVD group, P= 0.002), reaching the predetermined boundaries for termination of the trial. We demonstrated a better favorable outcome (modified Rankin Scale score 0-3) at 180 days in the intervention group, compared with the control group (35 [63.6%] vs. 24 [43.6%], P= 0.04). Participants in the intervention group experienced a higher IVH removal rate (91% [9.0] vs. 69.5% [38.0], P < 0.01) and had lower shunt conversion (1 [1.8%] vs. 16 [29.3%], P < 0.01). Treatment complications were comparable between the two groups. This study demonstrated that combined ES and IVF is safe and effective for the treatment of IVH. In addition, it concluded that aggressive but safe procedures used to remove IVH could improve clinical outcome in patients with IVH.

Hematoma clearance by reactive microglia after intracerebral hemorrhage

Intracerebral hemorrhage (ICH) is a subtype of stroke with high incidence rate and mortality. The pathogenesis of ICH involves primary brain injury and secondary brain injury. Unfortunately, no approved treatment options and therapies targeting them have shown satisfactory outcomes. Microglia are resident innate immune cells with phagocytic function in the central nervous system that rapidly respond to brain injury. Recent research has indicated that reactive microglia with enhanced phagocytosis reprogrammed by the interleukin 10 (IL-10) signaling pathway are critical for endogenous hematoma clearance. In this review, we first summarize the progress of microglial activation and function after ICH, focusing on specific microglial markers, pro- and anti-inflammatory molecules, as well as phenotypic and functional changes. The available evidence supports that microglia play a dual role after ICH. Second, we summarize the results of previous studies on hematoma clearance, focusing on reactive microglia in clearing hematoma through endogenous pathways reprogrammed by IL-10 or other molecules and necessitating the prospect of further research in this field. This review will help us better understand the role of reactive microglia in hematoma clearance and identify potential therapeutic targets to facilitate translational research in this direction.

Research progress of endogenous hematoma absorption after intracerebral hemorrhage.

Non-traumatic intraparenchymal brain hemorrhage is referred to as intracerebral hemorrhage (ICH). Although ICH is associated with a high rate of disability and case fatality, active intervention can significantly lower the rate of severe disability. Studies have shown that the speed of hematoma clearance after ICH determines the patient's prognosis. Following ICH, depending on the hematoma volume and mass effect, either surgical- or medication-only conservative treatment is chosen. The goal of promoting endogenous hematoma absorption is more relevant because surgery is only appropriate for a small percentage of patients, and open surgery can cause additional trauma to patients. The primary method of removing hematoma after ICH in the future will involve understanding how to produce and manage macrophage/microglial endogenous phagocytic hematomas. Therefore, it is necessary to elucidate the regulatory mechanisms and key targets for clinical purposes.

Safety and Efficacy of Stereotaxic Surgery Combined with Urokinase in the Treatment of Ventricular Hemorrhage: A Retrospective Propensity-Matched Score Analysis

Intraventricular hemorrhage (IVH) is a severe and devastating stroke. Research on existing treatment options has been controversial. Therefore, we aimed to evaluate the safety and efficacy of minimally implanted stereotactic puncture combined with urokinase (uPA) in the treatment of IVH. The clinical data of 122 IVH patients admitted to our department from 2018 to 2022 were retrospectively analyzed. According to the modified RanKin score (mRS) after 30days, the patients were divided into good prognosis (mRS 0-3) and poor prognosis (mRS 4-6), and the factors affecting the prognosis were screened by univariate and multivariate analysis, and then the tendency Score matching and paired patient screening were performed for comparative analysis between uPA and non-uPA groups. Patients' age, uPA usage, initial Glasgow Coma Scale and primary blood volume all could affect the mRS score of patients. One hundred patients were finally included, including 50 cases in the uPA group and 50 cases in the non-uPA group. The analysis showed that at follow-up after 30days, 46.0% of the patients in the uPA group and 28.0% in the non-uPA group had an mRS score of 0-3; however, they were not statistically significantly different. The postoperative hematoma clearance rate in the uPA group was significantly higher than that in the non-uPA group (P<0.001), and the incidence of postoperative complications was not increased (P>0.05). uPA treatment can improve the treatment efficiency. However, its effect in improving patient outcomes does not appear to be significant.

Efficacy and prognosis of neuroendoscopy-assisted surgery for chronic subdural hematoma.

This paper aims to analyze the clinical effect and prognosis of neuroendoscopy-assisted surgery for chronic subdural hematoma (CSDH). The clinical data of CSDH patients who underwent surgery between March 2018 and June 2020 in the Department of Neurosurgery of the First Affiliated Hospital of Xiamen University were retrospectively collected and analyzed. Eighty patients with CSDH who met the inclusive criteria were selected. A control group (32 cases treated with burr hole drainage) and an observation group (48 cases treated with neuroendoscopy-assisted surgery) were set according to different operation methods. The hematoma clearance rate, surgery-related indicators, related complications, hematoma recurrence rate and related prognostic indicators of the two groups were compared and analyzed. The postoperative hematoma clearance rate of the observation group was 92.59%, which was higher than that of the control group (77.78%) (P<0.05). The operation time of the observation group was longer than that of the control group (P<0.05). The postoperative hospitalization time of the observation group was shorter than that of the control group (P<0.05). The postoperative complication rate of the observation group was lower than that of the control group (P<0.05). The recurrence rate of hematoma in the observation group in the six-month postoperative follow-up was 1.85%, which was lower than that in the control group (P<0.05). The limb motor function and daily living ability score of the observation group were higher than those of the control group, and the Markwalder grading score was lower than that of the control group (P<0.05). Neuroendoscopy-assisted treatment which is safe and effective is superior to traditional burr-hole drainage surgery. It can reduce the recurrence rate; thus, it is worth advocating and applying.

Macrophage/Microglia Sirt3 Contributes to the Anti-inflammatory Effects of Resveratrol Against Experimental Intracerebral Hemorrhage in Mice.

Intracerebral hemorrhage (ICH) is a devastating stroke type with high mortality and disability. Inflammatory response induced by macrophages/microglia (M/Ms) activation is one of the leading causes of brain damage after ICH. The anti-inflammatory effects of resveratrol (RSV) have already been evaluated in several models of central nervous system disease. Therefore, we designed the current study to assess the role of RSV in ICH and explore its downstream mechanism related to Sirt3. The autologous artery blood injection was administrated to create an ICH mouse model. M/Ms-specific Sirt3 knockout Sirt3f/f; CX3CR1-Cre (Sirt3 cKO) mouse was used to evaluate the role of Sirt3 on RSV treatment. Neuronal function and hematoma volume were assessed to indicate brain damage. The pro-inflammatory marker (CD16) and cytokine (TNF) were measured to evaluate the inflammatory effects. Our results showed that RSV treatment alleviates neurological deficits, reduces cell death, and increases hematoma clearance on day 7 after ICH. In addition, RSV effectively suppressed CD16+ M/Ms activation and decreased TNF release. In Sirt3 cKO mice, the protective effects of RSV were abolished, indicating the potential mechanism of RSV was partially due to Sirt3 signaling activation. Therefore, RSV could be a promising candidate and therapeutic agent for ICH and Sirt3 could be a potential target to inhibit inflammation.

Neuroprotection by Nrf2 via modulating microglial phenotype and phagocytosis after intracerebral hemorrhage

Activated microglia are divided into pro-inflammatory and anti-inflammatory functional states. In anti-inflammatory state, activated microglia contribute to phagocytosis, neural repair and anti-inflammation. Nrf2 as a major endogenous regulator in hematoma clearance after intracerebral hemorrhage (ICH) has received much attention. This study aims to investigate the mechanism underlying Nrf2-mediated regulation of microglial phenotype and phagocytosis in hematoma clearance after ICH. In vitro experiments, BV-2 cells were assigned to normal group and administration group (Nrf2-siRNA, Nrf2 agonists Monascin and Xuezhikang). In vivo experiments, mice were divided into 5 groups: sham, ICH + vehicle, ICH + Nrf2−/−, ICH + Monascin and ICH + Xuezhikang. In vitro and in vivo, 72 h after administration of Monascin and Xuezhikang, the expression of Nrf2, inflammatory-associated factors such as Trem1, TNF-α and CD80, anti-inflammatory, neural repair and phagocytic associated factors such as Trem2, CD206 and BDNF were analyzed by the Western blot method. In vitro, fluorescent latex beads or erythrocytes were uptaken by BV-2 cells in order to study microglial phagocytic ability. In vivo, hemoglobin levels reflect the hematoma volume. In this study, Nrf2 agonists (Monascin and Xuezhikang) upregulated the expression of Trem2, CD206 and BDNF while decreased the expression of Trem1, TNF-α and CD80 both in vivo and in vitro. At the same time, after Monascin and Xuezhikang treatment, the phagocytic capacity of microglia increased in vitro, neurological deficits improved and hematoma volume lessened in vivo. These results were reversed in the Nrf2-siRNA or the Nrf2−/− mice. All these results indicated that Nrf2 enhanced hematoma clearance and neural repair, improved neurological outcomes through enhancing microglial phagocytosis and alleviating neuroinflammation.

Use of Novel Automated Active Irrigation With Drainage Versus Passive Drainage Alone for Chronic Subdural Hematoma-A Propensity Score-Matched Comparative Study With Volumetric Analysis.

Passive drainage post-surgical evacuation of symptomatic chronic subdural hematoma (cSDH) is currently standard of care. High rates of infection, drain occlusion, and recurrence are associated complications. To explore the use of a novel double-lumen active automated irrigation and aspiration system, IRRAflow (IRRAS), for patients with cSDH and compared procedural and clinical outcomes against passive drainage alone with propensity score matching (PSM) and volumetric analysis. A prospectively maintained database was retrospectively searched for consecutive patients presenting with cSDH. One-to-one PSM of covariates (including baseline comorbidities and presentation hematoma volume) in active and passive irrigation groups was performed to adjust for treatment selection bias. Rates of hematoma clearance, catheter-related occlusion, and infection; number of revisions; and length of hospital stay were recorded. This study included 55 patients: active continuous irrigation-drainage-21 (21 post-PSM) and passive drainage-34 (21 post-PSM). For PSM groups, a significantly higher rate of hematoma clearance was obtained in the active irrigation-drainage group (0.5 ± 0.4 vs 0.4 ± 0.5 mL/day) and in the passive drainage group; odds ratio (OR) = 1.291 (CI: 1.062-1.570, P = .002) and a significantly lower rate of catheter-related infections (OR = 0.051; CI: 0.004-0.697, P = .039). A nonsignificantly lower hematoma expansion rate at discharge was noted in the active irrigation-drainage group (4.8% vs 23.8%; OR = 0.127; P = .186). No statistical difference in all-cause in-hospital mortality or discharge Glasgow Coma Scale score was observed between groups. Active and automated continuous irrigation plus drainage after cSDH surgical evacuation resulted in faster hematoma clearance and led to favorable clinical outcomes and low complication and revision rates compared with passive irrigation.

Intraoperative ultrasound is valuable for detecting intracranial hematoma progression and decreasing mortality in traumatic brain injury.

Our aim was to explore the clinical benefit of intraoperative ultrasound in decompressive craniectomy (DC) for traumatic brain injury (TBI). From January 1, 2018, through April 30, 2021, 54 patients who developed acute subdural hematoma (SDH) due to blunt injury and underwent DC with or without intraoperative ultrasound assistance were retrospectively included in our study. Logistic regression analyses were performed to compare the therapeutic efficacy in the two groups. In the ultrasound group (14 patients, 25.93%), intraoperative ultrasound was used for assisting hematoma removal and/or ventriculostomy during DC. In the control group (40 patients, 74.07%), ultrasound was not used during the operation and ventriculostomy was not performed. No statistically significant differences in age, sex, initial Glasgow Coma Scale (GCS) score, blood loss, postoperative intracranial pressure (ICP), duration of hyperosmolar therapy, or Glasgow Outcome Scale Extended (GOS-E) score 6months after injury were observed. No mortality was recorded in the ultrasound group. The mortality rate in the control group during hospitalization was 25% (p < 0.05). Intraoperative ultrasound is helpful for intracranial hematoma removal and ventriculostomy with cerebrospinal fluid drainage and decreases mortality in experienced hands. The reason for higher mortality rate in the control group might result from poor hematoma clearance rate and poor postoperative intracranial pressure control. It is a useful tool for diagnosing and assisting with treatment in cases of TBI.

Magnetic Targeting Nanocarriers Combined with Focusing Ultrasound for Enhanced Intracerebral Hemorrhage Therapy.

Intracerebral hemorrhage (ICH) remains a significant cause of morbidity and mortality around the world, and surgery is still the most direct and effective way to remove ICH. However, the potential risks brought by surgery, such as normal brain tissue damage, post-operative infection, and difficulty in removing deep hematoma, are still the main problems in the surgical treatment of ICH. Activation of the peroxisome proliferator-activated receptor gamma (PPARγ) is reported to show a good therapeutic effect in hematoma clearance. Herein, a magnetic targeting nanocarrier loaded with a PPARγ agonist (15d-PGJ2-MNPs) is synthesized, which could be magnetically targeted and enriched in the area of the hematoma after intravenous injection. Subsequent application of focusing ultrasound (FUS) could enhance drug diffusion, which activates the PPARγ receptors on macrophages around the hematoma for better hematoma clearance. The 15d-PGJ2-MNP treatment alleviates brain injury, accelerates hematoma clearance, attenuates neuroinflammation, reduces brain edema and significantly improves the deficits in sensory and motor function and spatial learning ability in the ICH mouse model. This work proposes an effective magnetic targeting plus FUS method to treat ICH, highlighting its great potential in the treatment of hemorrhagic stroke.

Inhibition of the LRRC8A channel promotes microglia/macrophage phagocytosis and improves outcomes after intracerebral hemorrhagic stroke.

Promoting microglial/macrophage (M/Mφ) phagocytosis accelerates hematoma clearance and improves the prognosis of intracerebral hemorrhagic stroke (ICH). Cation channels such as Piezo1 modulate bacterial clearance by regulating M/Mφ. Whether LRRC8A, an anion channel, affects M/Mφ erythrophagocytosis and functional recovery after ICH was investigated here. We found that LRRC8A is highly expressed on M/Mφ in the perihematomal region of ICH mice. Conditional knockout of Lrrc8a in M/Mφ or treatment with an LRRC8A channel blocker accelerated hematoma clearance, reduced neuronal death, and improved functional recovery after ICH. Mechanistically, the LRRC8A channel inhibition promoted M/Mφ phagocytosis by activating AMP-activated protein kinase (AMPK), thereby inducing nuclear translocation of nuclear factor-erythroid 2 related factor 2 (Nrf2) and increasing Cd36 transcription. Our findings illuminate the regulation of M/Mφ phagocytosis by the LRRC8A channel via the AMPK-Nrf2-CD36 pathway after ICH, suggesting that LRRC8A is a potential target for hematoma clearance in ICH treatment.

Early, Intense Rehabilitation Fails to Improve Outcome After Intra-Striatal Hemorrhage in Rats

Background The formation and degradation of an intracerebral hemorrhage causes protracted cell death, and an extended window for intervention. Experimental studies find that rehabilitation mitigates late cell death, with accelerated hematoma clearance as a potential mechanism. Objective We assessed whether early, intense, enriched rehabilitation (ER, environmental enrichment and massed skills training) enhances functional benefit, reduces brain injury, and augments hematoma clearance. Methods In experiment 1, rats (n = 56) were randomized to intervention in the light (-L) or dark phase (-D) of their housing cycle, then to 10 days of ER or control (CON) treatment after collagenase-induced striatal intracerebral hemorrhage (ICH). ER rats were treated from 5 to 14 days after ICH. Behavior and residual hematoma volume was assessed on day 14. In experiment 2, rats (n = 72) were randomized to ER-D10, ER-D20, or CON-D. ER rats completed 10 or 20 days of training in the dark. Rats were euthanized on day 60 for histology. In both experiments, behavioral assessment was completed pre-ICH, pre-ER (day 4 post-ICH), and post-ER (experiment 1: days 13-14; experiment 2: days 16-17 and 30-31). Results Reaching intensity was high but similar between ER-D10 and ER-L10. Unlike previous work, rehabilitation did not alter skilled reaching or hematoma resolution. Varying ER duration also did not affect reaching success or lesion volume. Conclusions In contrast to others, and under these conditions, our findings show that striatal ICH was generally unresponsive to rehabilitation. This highlights the difficulty of replicating and extending published work, perhaps owing to small inter-study differences.

Modified exosomal SIRPα variants alleviate white matter injury after intracerebral hemorrhage via microglia/macrophages

BackgroundDespite limited efficiency, modulation of microglia/macrophages has shown to attenuate neuroinflammation after intracerebral hemorrhage (ICH). In this context, we evaluated the efficacy of modified exosomal signal regulatory protein α (SIRPα) variants (SIRPα-v Exos) in microglia/macrophages and neuroinflammation-associated white matter injury after ICH.MethodsSIRPα-v Exos were engineered to block CD47-SIRPα interactions. After obtaining SIRPα-v Exos from lentivirus-infected mesenchymal stem cells, C57BL/6 mice suffering from ICH underwent consecutive intravenous injections of SIRPα-v Exos (6 mg/kg) for 14 days. Afterwards, the volume of hematoma and neurological dysfunctions were assessed in mice continuously until 35 days after ICH. In addition, demyelination, electrophysiology and neuroinflammation were evaluated. Furthermore, the mechanisms of microglial regulation by SIRPα-v Exos were investigated in vitro under coculture conditions.ResultsThe results demonstrated that the clearance of hematoma in mice suffering from ICH was accelerated after SIRPα-v Exo treatment. SIRPα-v Exos improved long-term neurological dysfunction by ameliorating white matter injury. In addition, SIRPα-v Exos recruited regulatory T cells (Tregs) to promote M2 polarization of microglia/macrophages in the peri-hematoma tissue. In vitro experiments further showed that SIRPα-v Exos regulated primary microglia in a direct and indirect manner in synergy with Tregs.ConclusionOur studies revealed that SIRPα-v Exos could accelerate the clearance of hematoma and ameliorate secondary white matter injury after ICH through regulation of microglia/macrophages. SIRPα-v Exos may become a promising treatment for ICH in clinical practice.Graphical

Prognosis and Influencing Factors of Early Microsurgery for Severe Hypertensive Brainstem Hemorrhage.

Objective To investigate the prognosis and influencing factors of early microsurgery for severe hypertensive brainstem hemorrhage. Methods The clinical data of 19 patients with severe hypertensive brainstem hemorrhage treated in the Department of Neurosurgery of the Second Affiliated Hospital of Shandong First Medical University between January 2018 and December 2021 were retrospectively analyzed. The clinical efficacy and risk factors affecting the prognosis were analyzed by chi-square test and multivariate logistic regression. Results A total of 19 patients with severe hypertensive brainstem hemorrhage were treated by early microsurgery, including 14 cases by subtemporal approach and 5 cases by retrosigmoid approach. After 3 months of follow-up, 6 patients died and 13 patients survived. The 30-day and 90-day mortality rates were 21.1% and 31.6%, respectively, and the good prognosis rate was 15.4%. Univariate analysis showed that hematoma volume and hematoma clearance rate might be the factors affecting the prognosis of patients with severe hypertensive brainstem hemorrhage; the observed difference was statistically significant (P < 0.05). Multivariate logistic regression analysis further confirmed that hematoma volume was an independent factor affecting the death of patients with brainstem hemorrhage (P < 0.05), while hematoma volume (B: 2.909, OR: 18.332, 95% CI: 1.020–329.458, P: 0.048) was a risk factor. Conclusion Hematoma volume resulted as an independent factor affecting the death of patients with severe hypertensive brainstem hemorrhage. Early microsurgical clearance of brainstem hematoma contributed to reducing the 30-day and 90-day mortality and improving the prognosis of patients.

Pulsed Electromagnetic Field Protects Against Brain Injury After Intracerebral Hemorrhage: Involvement of Anti-Inflammatory Processes and Hematoma Clearance via CD36.

Intracerebral hemorrhage causes high mortality and morbidity, but its therapy methods are limited. In the present study, pulsed electromagnetic field (PEMF) was demonstrated to have beneficial effects on an intracerebral hemorrhage (ICH) model. This study explored the effects and underlying mechanisms of PEMF in a mouse model of ICH and cultured BV2 cells. PEMF was applied 4hours after collagenase-induced ICH at day 0 and 4hours per day for seven consecutive days. The expression levels of proinflammatory factors were assessed by ELISA kits and western blotting. Hematoma volume was measured by histological analysis. The effects of PEMF on phagocytosis of the erythrocytes were observed in cultured BV2 cells and ICH mouse models. Seven days after ICH, the hematoma volume was significantly reduced in PEMF-treated animals compared to nontreated mice. We found that PEMF decreased the hematoma volume and the expression levels of proinflammatory factors after ICH. Moreover, PEMF enhanced the erythrophagocytosis of microglia via CD36. Furthermore, we found that downregulation CD36 with Genistein blocked the effects of PEMF-induced hematoma clearance and anti-inflammations effects. Thus, the PEMF-mediated promotion of neurological functions may at least partly involve anti-inflammatory processes and hematoma clearance. These results suggest that PEMF treatment promoted the hematoma clearance and alleviated the inflammation after ICH.