Neurosurgery at the crossroads of immunology and nanotechnology. New reality in the COVID-19 pandemic.

Neurosurgery as one of the most technologically demanding medical fields rapidly adapts the newest developments from multiple scientific disciplines for treating brain tumors. Despite half a century of clinical trials, survival for brain primary tumors such as glioblastoma (GBM), the most common primary brain cancer, or rare ones including primary central nervous system lymphoma (PCNSL), is dismal. Cancer therapy and research have currently shifted toward targeted approaches, and personalized therapies. The orchestration of novel and effective blood-brain barrier (BBB) drug delivery approaches, targeting of cancer cells and regulating tumor microenvironment including the immune system are the key themes of this review. As the global pandemic due to SARS-CoV-2 virus continues, neurosurgery and neuro-oncology must wrestle with the issues related to treatment-related immune dysfunction. The selection of chemotherapeutic treatments, even rare cases of hypersensitivity reactions (HSRs) that occur among immunocompromised people, and number of vaccinations they have to get are emerging as a new chapter for modern Nano neurosurgery.

Perioperative clinical trials for glioma: Raising the bar.

Gliomas are a heterogeneous group of primary brain cancers with poor survival despite multimodality therapy that includes surgery, radiation and chemotherapy. Numerous clinical trials have investigated systemic therapies in glioma, but have largely been negative. Multiple factors have contributed to the lack of progress including tumour heterogeneity, the tumour micro-environment and presence of the blood-brain barrier, as well as extrinsic factors relating to trial design, such as the lack of a contemporaneous biopsy at the time of treatment. A number of strategies have been proposed to progress new agents into the clinic. Here, we review the progress of perioperative, including phase 0 and 'window of opportunity', studies and provide recommendations for trial design in the development of new agents for glioma. The incorporation of pre- and post-treatment biopsies in glioma early phase trials will provide valuable pharmacokinetic and pharmacodynamic data and also determine the target or biomarker effect, which will guide further development of new agents. Perioperative 'window of opportunity' studies must use drugs with a recommended-phase-2-dose, known safety profile and adequate blood-brain barrier penetration. Drugs shown to have on-target effects in perioperative trials can then be evaluated further in a larger cohort of patients in an adaptive trial to increase the efficiency of drug development.

Non-invasive, neurotoxic surgery reduces seizures in a rat model of temporal lobe epilepsy.

Surgery can be highly effective for treating certain cases of drug resistant epilepsy. The current study tested a novel, non-invasive, surgical strategy for treating seizures in a rat model of temporal lobe epilepsy. The surgical approach uses magnetic resonance-guided, low-intensity focused ultrasound (MRgFUS) in combination with intravenous microbubbles to open the blood-brain barrier (BBB) in a transient and focal manner. During the period of BBB opening, a systemically administered neurotoxin (Quinolinic Acid: QA) that is normally impermeable to the BBB gains access to a targeted area in the brain, destroying neurons where the BBB has been opened. This strategy is termed Precise Intracerebral Non-invasive Guided Surgery (PING). Spontaneous recurrent seizures induced by pilocarpine were monitored behaviorally prior to and after PING or under control conditions. Seizure frequency in untreated animals or animals treated with MRgFUS without QA exhibited expected seizure rate fluctuations frequencies between the monitoring periods. In contrast, animals treated with PING targeting the intermediate-temporal aspect of the hippocampus exhibited substantial reductions in seizure frequency, with convulsive seizures being eliminated entirely in two animals. These findings suggest that PING could provide a useful alternative to invasive surgical interventions for treating drug resistant epilepsy, and perhaps for treating other neurological disorders in which aberrant neural circuitries play a role.

Cranial MR-Guided Focused Ultrasound: Clinical Challenges and Future Directions.

Magnetic resonance-guided focused ultrasound is a powerful new technology that is enabling development of noninvasive applications for complex brain disorders. This is currently revolutionizing the treatment of tremor disorders, and a variety of experimental applications are under active investigation. To fully realize the potential of this disruptive technology, many challenges have been identified, some of which have been addressed and others remain to be solved. As an image-based technology, optimal intraoperative imaging can be difficult to achieve and several factors can influence the quality of these images. Technical issues with current devices can also limit the effective delivery of ultrasound technology to particular targets. While lesioning is the primary approved application of magnetic resonance-guided focused ultrasound at present, the ability to transient and precisely open the blood-brain barrier has the potential to clear brain pathologies and deliver restorative therapies, but this more experimental method presents unique difficulties to overcome. Finally, regulatory and reimbursement hurdles currently remain complex and continue to limit widespread application of even approved, effective applications. Here we review many of these challenges, discuss several solutions that have already been developed, and propose potential options for addressing some of these complexities in the future.

Innovative Applications of MR-Guided Focused Ultrasound for Neurological Disorders.

Magnetic resonance-guided focused ultrasound (MRgFUS) is a cutting-edge technology that is changing the practice of movement disorders surgery. Given the noninvasive and innovative nature of this technology, there is great interest in expanding the use of MRgFUS to additional diseases and applications. Current approved applications target the motor thalamus to treat tremor, but clinical trials are exploring or plan to study noninvasive lesions with MRgFUS to ablate tumor cells in the brain as well as novel targets for movement disorders and brain regions associated with pain and epilepsy. Although there are additional potential indications for lesioning, the ability to improve function by destroying parts of the brain is still limited. However, MRgFUS can also be applied to a brain target after intravenous delivery of microbubbles to create cavitations and focally open the blood-brain barrier (BBB). This has already proven to be safe and technically feasible in human patients with Alzheimer's disease, and this action alone has potential to clear extracellular pathology associated with this and other neurodegenerative disorders. This also provides a foundation for noninvasive intravenous delivery of therapeutic molecules to precise brain targets after transient disruption of the BBB. Certain chemotherapies for brain tumors, immunotherapies, gene, and cell therapies are all examples of therapeutic or even restorative agents that normally will not enter the brain without direct infusion but which have been shown in preclinical studies to effectively traverse the BBB after transient disruption with MRgFUS. Here we will review these novel applications of MRgFUS to provide an overview of the extraordinary potential of this technology to expand future neurosurgical treatments of brain diseases.

An electric-field-responsive paramagnetic contrast agent enhances the visualization of epileptic foci in mouse models of drug-resistant epilepsy.

For patients with drug-resistant focal epilepsy, excision of the epileptogenic zone is the most effective treatment approach. However, the surgery is less effective in the 15-30% of patients whose lesions are not distinct when visualized by magnetic resonance imaging (MRI). Here, we show that an intravenously administered MRI contrast agent consisting of a paramagnetic polymer coating encapsulating a superparamagnetic cluster of ultrasmall superparamagnetic iron oxide crosses the blood-brain barrier and improves lesion visualization with high sensitivity and target-to-background ratio. In kainic-acid-induced mouse models of drug-resistant focal epilepsy, electric-field changes in the brain associated with seizures trigger breakdown of the contrast agent, restoring the T1-weighted magnetic resonance signal, which otherwise remains quenched due to the distance-dependent magnetic resonance tuning effect between the cluster and the coating. The electric-field-responsive contrast agent may increase the probability of detecting seizure foci in patients and facilitate the study of brain diseases associated with epilepsy.

The impact of fluorescein-guided technique in the surgical removal of CNS tumors in a pediatric population: results from a multicentric observational study.

BACKGROUND: Surgery has a fundamental role in central nervous system (CNS) tumors in the pediatric population, as aggressive resection correlates with prognosis. Due to its accumulation in areas with damaged blood brain barrier, sodium fluorescein (SF) could be a valid tool to improve the extent of resection in tumors enhancing at preoperative MRI. This study is aimed to systematically assess the utility of SF in a pediatric population. METHODS: Patient data were collected in two centers, one in Italy and the other in Germany. At the induction of anesthesia, SF was administered intravenously (5 mg/kg). Surgery was performed using a YELLOW560 filter. Fluorescence intensity was graduated as bright, moderate or absent based on surgeon's opinion; furthermore, SF use was judged as "helpful," "not helpful" or "not essential" in tumor removal. RESULTS: Twenty-four patients for 27 surgical procedures were identified. In 21 of 27 (77.8%) procedures fluorescence was reported as bright or moderate, in two of 27 (7.4%) absent and in four of 27 (14.8%) data were unavailable. Intraoperative fluorescence was reported in 21 of 25 (84%) surgeries whose corresponding preoperative MRI had shown contrast enhancement. In 14 of 27 (51.8%) surgical procedures SF was considered "helpful"; in two of 27 (7.4%) not "helpful"; in seven of 27 (25.9%) "not essential." In four of 27 (14.8%) data were unavailable. No adverse effect to SF was registered. CONCLUSIONS: SF could be considered a valid and safe tool to improve visualization of tumors enhancing at preoperative MRI also in pediatric patients. Future prospective studies are needed to confirm these preliminary data.

Real-time MRI guidance for intra-arterial drug delivery in a patient with a brain tumor: technical note.

Patients with malignant brain tumors have a poor prognosis. The blood-brain barrier (BBB) is considered a primary obstacle in therapeutic drug delivery to the brain. Intra-arterial (IA) delivery of therapeutic agents following osmotic BBB opening has been attempted for years, but high variability has limited its widespread implementation. It has recently been shown in animal studies that MRI is superior to X-ray for guiding IA infusions, as it allows direct visualization of the brain parenchyma supplied by the catheter and facilitates predictable drug targeting. Moreover, PET imaging has shown that IA rather than intravenous delivery of bevacizumab results in accumulation in the brain, providing a strong rationale for using the IA route. We present a patient with recurrent butterfly glioblastoma enrolled in a first-in-man MRI-guided neurointervention for targeted IA drug delivery.

Blood-brain barrier and foetal-onset hydrocephalus, with a view on potential novel treatments beyond managing CSF flow.

Despite decades of research, no compelling non-surgical therapies have been developed for foetal hydrocephalus. So far, most efforts have pointed to repairing disturbances in the cerebrospinal fluid (CSF) flow and to avoid further brain damage. There are no reports trying to prevent or diminish abnormalities in brain development which are inseparably associated with hydrocephalus. A key problem in the treatment of hydrocephalus is the blood-brain barrier that restricts the access to the brain for therapeutic compounds or systemically grafted cells. Recent investigations have started to open an avenue for the development of a cell therapy for foetal-onset hydrocephalus. Potential cells to be used for brain grafting include: (1) pluripotential neural stem cells; (2) mesenchymal stem cells; (3) genetically-engineered stem cells; (4) choroid plexus cells and (5) subcommissural organ cells. Expected outcomes are a proper microenvironment for the embryonic neurogenic niche and, consequent normal brain development.

Blood-Brain Barrier Closure Time After Controlled Ultrasound-Induced Opening Is Independent of Opening Volume.

OBJECTIVES: Microbubble-mediated focused ultrasound (US) opening of the blood-brain barrier (BBB) has shown promising results for the treatment of brain tumors and conditions such as Alzheimer disease. Practical clinical implementation of focused US treatments would aim to treat a substantial portion of the brain; thus, the safety of opening large volumes must be investigated. This study investigated whether the opened volume affects the time for the BBB to be restored after treatment. METHODS: Sprague Dawley rats (n = 5) received bilateral focused US treatments. One hemisphere received a single sonication, and the contralateral hemisphere was targeted with 4 overlapping foci. Contrast-enhanced T1-weighted magnetic resonance imaging was used to assess the integrity of the BBB at 0, 6, and 24 hours after focused US. RESULTS: At time 0, there was no significant difference in the mean enhancement between the single- and multi-point sonications (mean ± SD, 29.7% ± 18.4% versus 29.7% ± 24.1%; P = .9975). The mean cross-sectional area of the BBB opening resulting from the multi-point sonication was approximately 3.5-fold larger than that of the single-point case (14.2 ± 4.7 versus 4.1 ± 3.3 mm2 ; P < .0001). The opened volumes in 9 of 10 hemispheres were closed by 6 hours after focused US. The remaining treatment location had substantially reduced enhancement at 6 hours and was closed by 24 hours. Histologic analysis revealed small morphologic changes associated with this location. T2-weighted images at 6 and 24 hours showed no signs of edema. T2*-weighted images obtained at 6 hours also showed no signs hemorrhage in any animal. CONCLUSIONS: The time for the BBB to close after focused US was independent of the opening volume on the time scale investigated. No differences in treatment effects were observable by magnetic resonance imaging follow-up between larger- and smaller-volume sonications, suggesting that larger-volume BBB opening can be performed safely.

Clinical trial of blood-brain barrier disruption by pulsed ultrasound.

The blood-brain barrier (BBB) limits the delivery of systemically administered drugs to the brain. Methods to circumvent the BBB have been developed, but none are used in standard clinical practice. The lack of adoption of existing methods is due to procedural invasiveness, serious adverse effects, and the complications associated with performing such techniques coincident with repeated drug administration, which is customary in chemotherapeutic protocols. Pulsed ultrasound, a method for disrupting the BBB, was shown to effectively increase drug concentrations and to slow tumor growth in preclinical studies. We now report the interim results of an ultrasound dose-escalating phase 1/2a clinical trial using an implantable ultrasound device system, SonoCloud, before treatment with carboplatin in patients with recurrent glioblastoma (GBM). The BBB of each patient was disrupted monthly using pulsed ultrasound in combination with systemically injected microbubbles. Contrast-enhanced magnetic resonance imaging (MRI) indicated that the BBB was disrupted at acoustic pressure levels up to 1.1 megapascals without detectable adverse effects on radiologic (MRI) or clinical examination. Our preliminary findings indicate that repeated opening of the BBB using our pulsed ultrasound system, in combination with systemic microbubble injection, is safe and well tolerated in patients with recurrent GBM and has the potential to optimize chemotherapy delivery in the brain.

Dural Arteriovenous Fistula Mimicking a Supratentorial Tumor.

BACKGROUND: The pathophysiology of dural arteriovenous fistulas (dAVF) is not fully understood. Retrograde venous flow can lead to venous congestion and disruption of the blood-brain barrier, resulting in diffuse contrast enhancement. CASE DESCRIPTION: We present the case of a patient with a supratentorial dAVF associated with a solid, tumor-appearing, corticosubcortical contrast-enhancing lesion. Surgical occlusion of the dAVF was followed by complete regression of the contrast-enhancing lesion. Histologic analysis of the lesion showed normal brain tissue. CONCLUSIONS: This case report highlights how venous congestion is an important differential diagnosis in contrast-enhancing lesions associated with dAVF and how it should be taken in consideration to avoid radiologic misdiagnoses and unnecessary treatment.

Long-Term Safety of Repeated Blood-Brain Barrier Opening via Focused Ultrasound with Microbubbles in Non-Human Primates Performing a Cognitive Task.

Focused Ultrasound (FUS) coupled with intravenous administration of microbubbles (MB) is a non-invasive technique that has been shown to reliably open (increase the permeability of) the blood-brain barrier (BBB) in multiple in vivo models including non-human primates (NHP). This procedure has shown promise for clinical and basic science applications, yet the safety and potential neurological effects of long term application in NHP requires further investigation under parameters shown to be efficacious in that species (500 kHz, 200-400 kPa, 4-5 µm MB, 2 minute sonication). In this study, we repeatedly opened the BBB in the caudate and putamen regions of the basal ganglia of 4 NHP using FUS with systemically-administered MB over 4-20 months. We assessed the safety of the FUS with MB procedure using MRI to detect edema or hemorrhaging in the brain. Contrast enhanced T1-weighted MRI sequences showed a 98% success rate for openings in the targeted regions. T2-weighted and SWI sequences indicated a lack edema in the majority of the cases. We investigated potential neurological effects of the FUS with MB procedure through quantitative cognitive testing of' visual, cognitive, motivational, and motor function using a random dot motion task with reward magnitude bias presented on a touchpanel display. Reaction times during the task significantly increased on the day of the FUS with MB procedure. This increase returned to baseline within 4-5 days after the procedure. Visual motion discrimination thresholds were unaffected. Our results indicate FUS with MB can be a safe method for repeated opening of the BBB at the basal ganglia in NHP for up to 20 months without any long-term negative physiological or neurological effects with the parameters used.

Heterotopic mucosal engrafting procedure for direct drug delivery to the brain in mice.

Delivery of therapeutics into the brain is impeded by the presence of the blood-brain barrier (BBB) which restricts the passage of polar and high molecular weight compounds from the bloodstream and into brain tissue. Some direct delivery success in humans has been achieved via implantation of transcranial catheters; however this method is highly invasive and associated with numerous complications. A less invasive alternative would be to dose the brain through a surgically implanted, semipermeable membrane such as the nasal mucosa that is used to repair skull base defects following endoscopic transnasal tumor removal surgery in humans. Drug transfer though this membrane would effectively bypass the BBB and diffuse directly into the brain and cerebrospinal fluid. Inspired by this approach, a surgical approach in mice was developed that uses a donor septal mucosal membrane engrafted over an extracranial surgical BBB defect. This model has been shown to effectively allow the passage of high molecular weight compounds into the brain. Since numerous drug candidates are incapable of crossing the BBB, this model is valuable for performing preclinical testing of novel therapies for neurological and psychiatric diseases.

Intracerebroventricular transplantation of ex vivo expanded endothelial colony-forming cells restores blood-brain barrier integrity and promotes angiogenesis of mice with traumatic brain injury.

Endothelial progenitor cells (EPCs) play a key role in tissue repair and regeneration. Previous studies have shown a positive correlation between the number of circulating EPCs and clinical outcomes of patients with traumatic brain injury (TBI). A recent study has further shown that intravenous infusion of human umbilical cord blood-derived endothelial colony-forming cells (ECFCs) improves outcomes of mice subjected to experimental TBI. This follow-up study was designed to determine whether intracerebroventricular (i.c.v.) infusion of ECFCs, which may reduce systemic effects of these cells, could repair the blood-brain barrier (BBB) and promote angiogenesis of mice with TBI. Adult nude mice were exposed to fluid percussion injury and transplanted i.c.v. with ECFCs on day 1 post-TBI. These ECFCs were detected at the TBI zone 3 days after transplantation by SP-DiIC18(3) and fluorescence in situ hybridization. Mice with ECFCs transplant had reduced Evans blue extravasation and brain water content, increased expression of ZO-1 and claudin-5, and showed a higher expression of angiopoietin 1. Consistent with the previous report, mice with ECFCs transplant had also increased microvascular density. Modified neurological severity score and Morris water maze test indicated significant improvements in motor ability, spatial acquisition and reference memory in mice receiving ECFCs, compared to those receiving saline. These data demonstrate the beneficial effects of ECFC transplant on BBB integrity and angiogenesis in mice with TBI.

Neuronavigation-guided focused ultrasound-induced blood-brain barrier opening: a preliminary study in swine.

BACKGROUND AND PURPOSE: FUS-induced BBB opening is a promising technique for noninvasive and local delivery of drugs into the brain. Here we propose the novel use of a neuronavigation system to guide the FUS-induced BBB opening procedure and investigate its feasibility in vivo in large animals. MATERIALS AND METHODS: We developed an interface between the neuronavigator and FUS to allow guidance of the focal energy produced by the FUS transducer. The system was tested in 29 swine by more than 40 sonication procedures and evaluated by MR imaging. Gd-DTPA concentration was quantitated in vivo by MR imaging R1 relaxometry and compared with ICP-OES assay. Brain histology after FUS exposure was investigated using H&E and TUNEL staining. RESULTS: Neuronavigation could successfully guide the focal beam, with precision comparable to neurosurgical stereotactic procedures (2.3 ± 0.9 mm). A FUS pressure of 0.43 MPa resulted in consistent BBB opening. Neuronavigation-guided BBB opening increased Gd-DTPA deposition by up to 1.83 mmol/L (a 140% increase). MR relaxometry demonstrated high correlation with ICP-OES measurements (r(2) = 0.822), suggesting that Gd-DTPA deposition can be directly measured by imaging. CONCLUSIONS: Neuronavigation provides sufficient precision for guiding FUS to temporally and locally open the BBB. Gd-DTPA deposition in the brain can be quantified by MR relaxometry, providing a potential tool for the in vivo quantification of therapeutic agents in CNS disease treatment.

Fístula de líquido cefalorraquídeo recidivante postraumática asociada a meningocele esfenoidal. Técnica abierta-endoscópica / Cerebrospinal fluid fistula associated with posttraumatic recurrent sphenoidal meningocele. Open-endoscopic technique

Introducción. Las fístulas de líquido cefalorraquídeo surgen tras la ruptura de las barreras que separan la cavidad nasal y senos paranasales de los espacios subaracnoideos: base craneal, duramadre y membrana aracnoidea. Aproximadamente el 80% surgen en el contexto de traumatismos craneofaciales con fracturas de la base craneal. La elección del abordaje y técnica quirúrgica más adecuada en cada caso es esencial para la obtención de resultados quirúrgicos globales satisfactorios. El desarrollo de la cirugía endoscópica endonasal ha supuesto un arma terapéutica menos invasiva y eficaz, siendo las fístulas de líquido cefalorraquídeo una indicación bien establecida para su tratamiento definitivo. Caso clínico. Se presenta el caso de una paciente con fístula de líquido cefalorraquídeo recurrente con meningoencefalocele asociado tratada vía endoscópica. Discusión. Se discute el tratamiento conservador versus quirúrgico de las fístulas de líquido cefalorraquídeo. Ventajas y desventajas de los distintos tipos de abordajes relacionados con el manejo definitivo(AU)

Introduction. Cerebrospinal fluid fistulas arise after the breakdown of the barriers that separate the nasal cavity and paranasal sinuses of the subarachnoid space, skull base, dura and arachnoid membrane. Approximately 80% arise in the context of craniofacial trauma with fractures of the skull base. The choice of approach, appropriate surgical technique in each case is essential to achieve a good overall surgical outcome. Development of endoscopic endonasal surgery has become a less invasive and effective therapeutic tool, with cerebrospinal fluid fistulas being a well-established indication for definitive treatment. Case report. A case of a patient with cerebrospinal fluid fistula associated with recurrent meningoencephalocele, treated endoscopically. Discussion. We discuss the surgical versus conservative treatment of spinal fluid fistulas, and the advantages and disadvantages of different types of approaches related to definitive management(AU)

The pathophysiological time window study of performing minimally invasive procedures for the intracerebral hematoma evacuation in rabbit.

The objective of this study was to observe the pathophysiological time window of performing minimally invasive procedures for the intracerebral hematoma evacuation. Thirty-six rabbits were randomly placed in either a normal control group (NC group, 6 rabbits), a model control group (MC group, 6 rabbits) or a minimally invasive group (MI group, 24 rabbits). A model of intracerebral hemorrhage (ICH) was established in the MC and MI groups. In the MI group, the intracerebral hematoma was evacuated by stereotactic minimally invasive procedures over 6h (6 rabbits), 12h (6 rabbits), 18 h (6 rabbits) and 24h (6 rabbits), following successful induction of ICH. All of the animals in each group were sacrificed 48 h after the successful induction of ICH. Perihematomal brain tissues were removed to determine the glutamate level, BBB permeability and brain water content (BWC). The perihematomal glutamate level, BBB permeability and the BWC in the MI group were significantly decreased compared with those of the MC group. Performing minimally invasive procedures for evacuation of ICH in 6h showed the most remarkable decrease of the glutamate level, BBB permeability and BWC, followed by a significant difference observed at 12h within the MI subgroups. Performing minimally invasive procedures in early stages after ICH for the hematoma evacuation could decrease the perihematomal glutamate level, BBB permeability and BWC significantly. The pathophysiological time window of minimally invasive procedures for hematoma evacuation might be 6-12h after hemorrhage.

MR-guided focused ultrasound for brain ablation and blood-brain barrier disruption.

MR-guided transcranial focused ultrasound (FUS) has been demonstrated as a non-invasive tool for treating various brain diseases. First, FUS can thermally ablate brain tissues under real-time MR thermometry monitoring. The MRI guidance significantly improves the precision of the thermal dose deposition. Second, in conjunction with microbubble contrast agents, FUS can reversibly disrupt the blood-brain barrier for delivery of macromolecular drugs to the brain parenchyma. This offers huge potential for treating brain diseases with a much higher local drug concentration than other drug delivery methods. In this chapter, a detailed protocol of MR-guided focused ultrasound for brain thermal ablation and BBB disruption in an animal research setting is presented.

Effects of minimally invasive puncture and drainage of intracranial hematoma on the blood-brain barrier in patients with cerebral hemorrhage.

The effects of minimally invasive surgery on the blood-brain barrier (BBB) of 30 patients with cerebral hemorrhage were investigated. Difference of the BBB index and serum MBP concentration were assessed in 15 cases of conservative treatment group and 15 cases of minimally invasive surgery group. The BBB index in minimally invasive surgery group was significantly lower than in conservative treatment group (P<0.05), and the BBB index in the two treatment groups was significantly higher than in control group (P<0.01). Serum MBP concentration in minimally invasive surgery group was significantly lower than in conservative treatment group (P<0.05), and that in the two treatment groups was significantly higher than in control group (P<0.01). It was suggested the permeability of BBB in patients with cerebral hemorrhage was increased, and BBB index and serum MBP concentration in patients with cerebral hemorrhage were increased. Minimally invasive surgery can reduce the lesion of cytotoxicity to BBB and cerebral edema.