Role of the prefrontal cortical protease TACE/ADAM17 in neurobehavioral responses to chronic stress during adolescence.

INTRODUCTION: Chronic adolescent stress profoundly affects prefrontal cortical networks regulating top-down behavior control. However, the neurobiological pathways contributing to stress-induced alterations in the brain and behavior remain largely unknown. Chronic stress influences brain growth factors and immune responses, which may, in turn, disrupt the maturation and function of prefrontal cortical networks. The tumor necrosis factor alpha-converting enzyme/a disintegrin and metalloproteinase 17 (TACE/ADAM17) is a sheddase with essential functions in brain maturation, behavior, and inflammatory responses. This study aimed to determine the impact of stress on the prefrontal cortex and whether TACE/ADAM17 plays a role in these responses. METHODS: We used a Lewis rat model that incorporates critical elements of chronic psychosocial stress, such as uncontrollability, unpredictability, lack of social support, and re-experiencing of trauma. RESULTS: Chronic stress during adolescence reduced the acoustic startle reflex and social interactions while increasing extracellular free water content and TACE/ADAM17 mRNA levels in the medial prefrontal cortex. Chronic stress altered various ethological behavioral domains in the observation home cages (decreased ingestive behaviors and increased walking, grooming, and rearing behaviors). A group of rats was injected intracerebrally either with a novel Accell™ SMARTpool TACE/ADAM17 siRNA or a corresponding siRNA vehicle (control). The RNAscope Multiplex Fluorescent v2 Assay was used to visualize mRNA expression. Automated puncta quantification and analyses demonstrated that TACE/ADAM17 siRNA administration reduced TACE/ADAM17 mRNA levels in the medial prefrontal cortex (59% reduction relative to control). We found that the rats that received prefrontal cortical TACE/ADAM17 siRNA administration exhibited altered eating patterns (e.g., increased food intake and time in the feeding zone during the light cycle). CONCLUSION: This study supports that the prefrontal cortex is sensitive to adolescent chronic stress and suggests that TACE/ADAM17 may be involved in the brain responses to stress.

Establishment of a successful robotic pediatric general surgery practice.

Robotic-assisted surgery (RAS) has a variety of theoretical advantages, including tremor filtration, optimal visualization, and improvement of surgeon ergonomics. Though it has achieved wide application in pediatric urology, the majority of pediatric general surgeons do not employ RAS. This study reports our institution's experience with RAS on a pediatric general surgery team. Following IRB approval, a retrospective review of all pediatric patients at our academic children's hospital who underwent RAS between 2017 and 2022 for pediatric general surgical conditions was performed. Patient demographics, operation performed, operating time, complications, and recovery were evaluated. A total of 159 children underwent RAS, increasing from 10 patients in 2017 to 59 patients in 2022. The median age and weight were 15.3 years and 76.4 kg, and 121 (76.1%) were female. The application of RAS was successful in all cases. There were no intraoperative complications and no conversions to an open approach. Eleven patients (6.9%) had unplanned presentations to the emergency department within 30 days. Five of these patients (3.1%) required admission to the hospital. This study demonstrates that the application of RAS in an academic pediatric general surgery practice is feasible and safe. The application of RAS to pediatric general surgery should continue to increase as operative teams increase their experience and comfort.Level of evidence Level IV.

Prefrontal cortical protease TACE/ADAM17 is involved in neuroinflammation and stress-related eating alterations.

Childhood traumatic stress profoundly affects prefrontal cortical networks regulating top-down control of eating and body weight. However, the neurobiological mechanisms contributing to trauma-induced aberrant eating behaviors remain largely unknown. Traumatic stress influences brain immune responses, which may, in turn, disrupt prefrontal cortical networks and behaviors. The tumor necrosis factor alpha-converting enzyme / a disintegrin and metalloproteinase 17 (TACE/ADAM17) is a sheddase with essential functions in brain maturation, behavior, and neuroinflammation. This study aimed to determine the role of TACE/ADAM17 on traumatic stress-induced disruption of eating patterns. We demonstrate a novel mechanistic connection between prefrontal cortical TACE/ADAM17 and trauma-induced eating behaviors. Fifty-two (52) adolescent Lewis rats (postnatal day, PND, 15) were injected intracerebrally either with a novel Accell™ SMARTpool ADAM17 siRNA or a corresponding siRNA vehicle. The RNAscope Multiplex Fluorescent v2 Assay was used to visualize mRNA expression. Observation cages were used to monitor ethological behaviors in a more naturalistic environment over long periods. We found that traumatic stress blunts startle reactivity and alter eating behaviors (increased intake and disrupted eating patterns). We also found that the rats that received prefrontal cortical TACE/ADAM17 siRNA administration exhibited decreased eating and increased grooming behaviors compared to controls. These changes were associated with decreased AIF-1 expression (a typical marker of microglia and neuroinflammation). This study demonstrates that prefrontal cortical TACE/ADAM17 is involved in neuroinflammation and may play essential roles in regulating feeding patterns under stress conditions. TACE/ADAM17 represents a promising target to ameliorate inflammation-induced brain and behavior alterations.

Current Open Surgical Indications for Revascularization in Cerebral Ischemia.

Cerebral revascularization was pioneered half a century ago. Gradual improvements in microsurgical instrumentation and training in microsurgical techniques have allowed significant changes that improved outcomes in neurosurgery, extrapolating this knowledge to other neurosurgical diseases (brain tumor, aneurysms, and skull base tumor surgery). But the popularity of cerebral bypass procedures was followed by their decline, given the lack of clear benefit of bypass surgery in chronic cerebrovascular ischemia after the EC-IC bypass studies. Over the last couple of decades, the formidable advance of neuro-endovascular techniques for revascularization has lessened the need for application of open cerebral revascularization procedures, either for flow augmentation or flow replacement. However, there is still a select group of patients with chronic cerebral ischemia, for whom open cerebral revascularization with flow augmentation is the only treatment option available, and this will be the objective of our current review.

Retractorless interhemispheric transtentorial approach for large lesions in the posterior incisural space.

BACKGROUND: Surgical resection of lesions in the posterior incisural space presents a significant surgical challenge, which may result in postoperative visual complications and other neurological deficits. We, therefore, describe a retractorless interhemispheric transtentorial approach that avoids surrounding brain structures with positive outcomes and no complications or visual damage. CASE DESCRIPTION: We present four cases of lesions in the posterior incisural space that was treated with a retractorless interhemispheric transtentorial approach. Two patients were previously seen at another institution for a falcotentorial meningioma. We resected the meningiomas with a parietal-occipital interhemispheric transtentorial approach with no neurological deficits. A third patient presented with a large superior vermian hemangioblastoma with a steep angle of the tentorium. The fourth patient had a large upper vermian metastatic lesion with progressive enlargement, which was refractory to radiation treatments and chemotherapy, and we achieved partial resection. Postoperative visual function was completely preserved in all patients. CONCLUSION: A carefully executed retractorless interhemispheric approach in select cases is an effective option to reduce morbidity and prevent visual complications when removing lesions in the posterior tentorial incisure.

Microsurgical Technique for Basilar Apex Aneurysm Clipping: Two-Dimensional Video.

We present the case of a 57-year-old female with hypertension, current smoker status, and recent headaches. Imaging studies showed an unruptured 8-mm basilar apex wide neck aneurysm located 4 mm above posterior clinoid (Figure 1) with a 3-mm anterior communicant artery aneurysm. No contraindications were encountered for endovascular treatment, although after we evaluated endovascular and surgical options, surgical clipping was considered also a safe and favorable option based on anterior projection of aneurysm, height of the basilar artery bifurcation, small and elongated posterior communicant artery, and available space between posterior clinoid and basilar artery (4 mm). The presence of a second aneurysm increased the patient's interest in a more definitive treatment, as we mentioned the possibility of its treatment if considered safe intraoperatively. A cranio-orbito-zygomatic craniotomy, anterior clinoidectomy, and sylvian fissure dissection was performed with electrophysiology monitoring. The exposure was enhanced by sphenoparietal sinus ligation, and the anterior clinoidectomy allowed working spaces at optic-carotid and carotid-oculomotor spaces for Liliequist membrane dissection, without need for posterior clinoid removal (Figure 2). Brief temporary clipping at basilar trunk below superior cerebellar arteries at perforating free zone was performed. Two clips were applied, obliterating adequately the aneurysm respecting perforating vessels. After the basilar apex aneurysm clipping, we proceeded in a standard fashion to clip the additional anterior communicant artery aneurysm. Micro-Doppler and intraoperative angiogram confirmed aneurysm exclusion and patent parent vessels (Video 1). The patient developed minimal ptosis due to partial right oculomotor nerve palsy that recovered completely in 2 weeks; otherwise, her neurologic exam was normal. At 1-year follow up, computed tomography angiography showed complete aneurysm exclusion.

A5 segment aneurysm of the anterior cerebral artery, imbedded into the body of the corpus callosum: A case report.

BACKGROUND: The A5 segment aneurysms of the anterior cerebral artery are rare, approximately 0.5% of all intracranial aneurysms. They are small with a wide base located in the midline, with the domes mostly projecting upward or backward. CASE DESCRIPTION: The authors describe a unique case of A5 segment aneurysm, with the dome embedded into the body of the corpus callosum. This 41-year-old female was admitted to the neurology department for possible multiple sclerosis investigation. Computed tomography angiogram (CTA) revealed a 4-mm right-sided pericallosal artery aneurysm, with rare configuration, which was caudally projected, embedded into the body of the corpus callosum. Considering the family history, patient underwent a prophylactic ligation surgery. The postoperative CT and CTA showed no complication and successful occlusion of the aneurysm with no ischemia or hemorrhage in the corpus callosum. CONCLUSION: To the best of our knowledge, this is the first case of an aneurysm with this configuration. Our rare case of A5 segment aneurysm demonstrates the importance of planning of the surgery, choosing the appropriate approach, and knowing the detailed anatomy of the region, as well as the necessity of microsurgical clipping of small unruptured AdistAs.

Short-Burst Bipolar Coagulation for Repairing Partially Damaged Brain Arteries Preserving Their Flow: Technical Note.

OBJECTIVE: Preservation of the integrity of perilesional and intralesional arteries, as well as of perforating vessels, is of utmost importance in microneurosurgery. The purpose of our study was to describe our adaptation of the short-burst bipolar coagulation technique, which was initially introduced by Professor Yasargil, for repairing partially damaged brain arteries. METHODS: When a brain artery is partially and inadvertently damaged during microneurosurgical procedures, microscope magnification is further increased from the high magnification that is routinely used (10-15×) up to 14-17× in order to recognize clearly the injured zone of the vessel. Then the exact bleeding point is identified with a precise suction. Next, bipolar forceps with sharp tips (0.3 mm) are used to seal the wall of the injured artery, closing the borders of the hole between them. A delicate coagulation (20 Malis units, 3 watts) is performed for less than a second according to the so-called "open-close" technique. Short and small bursts of coagulation are used to progressively reduce the size of the defect by cauterization of the surrounding tissue. This gradually diminishes the bleeding up to restore the functional integrity of the vessel wall. RESULTS: The senior author's modification of the Yasargil technique has been used for more than 30 years as a simple and fast method of microsurgical vascular repair of small tears. CONCLUSIONS: The bipolar coagulation represents a safe, clean, fast, and even cheap method for repairing wall defects in fine arteries that are accidently damaged during a microsurgical operation.

Clean, fast and preserving normal anatomy: "the Helsinki revolution" in microneurosurgery.

After the senior author took chairmanship in Helsinki University Hospital in, he led the department into making neurosurgical operations much faster, safer and workflow more efficient, and at the same time maintaining high surgical quality and results. The aim was to describe the philosophies and style of Helsinki Microneurosurgery. The philosophies of Helsinki Neurosurgery are categorized into two concepts: The operation room TEAM concept and the main principle "Simple, clean, fast and respecting the normal anatomy". The way to be efficient is to find good methods based on logic, reason and experience. Specific and systematic procedures before the microneurosurgery followed by high quality skills under the microscope are of utmost importance. Moreover, intraoperatively, neuroanesthesia has to provide good surgical conditions. Today, Helsinki University Central hospital Department of Neurosurgery has an annual workflow 3500 neurosurgical operations. We believe that microneurosurgical treatment remains to be important for years ahead, and neurosurgeons of great hearts, minds and skills are welcomed all over the world.