Jun-activated SOCS1 enhances ubiquitination and degradation of CCAAT/enhancer-binding protein ß to ameliorate cerebral ischaemia/reperfusion injury.

This study investigates the molecular mechanisms behind ischaemia/reperfusion (I/R) injury in the brain, focusing on neuronal apoptosis. It scrutinizes the role of the Jun proto-oncogene in apoptosis, involvement of SOCS1 in neural precursor cell accumulation in ischaemic regions, and the upregulation of C-EBPß in the hippocampus following I/R. Key to the study is understanding how Jun controls C-EBPß degradation via SOCS1, potentially offering new clinical treatment avenues for I/R. Techniques such as mRNA sequencing, KEGG enrichment analysis and protein-protein interaction (PPI) in mouse models have indicated involvement of Jun (AP-1) in I/R-induced cerebral damage. The study employs middle cerebral artery occlusion in different mouse models and oxygen-glucose deprivation/reoxygenation in cortical neurons to examine the impacts of Jun and SOCS1 manipulation on cerebral I/R injury and neuronal damage. The findings reveal that I/R reduces Jun expression in the brain, but its restoration lessens cerebral I/R injury and neuron death. Jun activates SOCS1 transcriptionally, leading to C-EBPß degradation, thereby diminishing cerebral I/R injury through the SOCS1/C-EBPß pathway. These insights provide a deeper understanding of post-I/R cerebral injury mechanisms and suggest new therapeutic targets for cerebral I/R injury. KEY POINTS: Jun and SOCS1 are poorly expressed, and C-EBPß is highly expressed in ischaemia/reperfusion mouse brain tissues. Jun transcriptionally activates SOCS1. SOCS1 promotes the ubiquitination-dependent C-EBPß protein degradation. Jun blunts oxygen-glucose deprivation/reoxygenation-induced neuron apoptosis and alleviates neuronal injury. This study provides a theoretical basis for the management of post-I/R brain injury.

E3 ubiquitin ligase COP1 confers neuroprotection in cerebral ischemia/reperfusion injury via regulation of transcription factor C/EBPß in microglia.

BACKGROUND: This study intends to investigate the potential involvement of E3 ubiquitin ligase COP1 in cerebral ischemia-reperfusion (I/R) injury. METHODS: A mouse model of middle cerebral artery occlusion/reperfusion (MCAO/R) was established, and the ischemic penumbra of mouse brain cortex was collected and subjected to RNA-sequencing (RNA-seq). Primary glial cells, neurons and astrocytes were isolated, and microglia were exposed to oxygen and glucose deprivation/reperfusion (OGD/R). RESULTS: COP1 was poorly expressed in MCAO mice and OGD/R microglia. Restoration of COP1 suppressed the activation of microglia and relieves neuroinflammation in cerebral I/R injury, leading to alleviated brain damage (infraction volume [%]: [31.58 ±â€¯2.96] & [12.06 ±â€¯1.29], neurological scores: [3.6 ±â€¯0.6] & [1.2 ±â€¯0.5]). COP1 promoted the ubiquitin-mediated degradation of C/EBPß in microglia. It was further revealed that COP1 attenuated microglia activation and phagocytosis (Iba + cells [N/mm2]: 182.68 ±â€¯20.89 & 84.57 ±â€¯12.08; soma area [µm2]: 78.24 ±â€¯8.75 & 59.78 ±â€¯7.61) through negative regulation of C/EBPß protein expression. Restoration of C/EBPßnegated the neuroprotective effects of COP1 in vivo. DISCUSSION: This study illuminated a mechanism by which COP1 conferred a neuroprotective role in cerebral I/R injury via enhancing the ubiquitin-mediated degradation of transcriptional factor C/EBPß in microglia.

Remote medulla ablongata ventral acute subarachnoid hemorrhage following cervical spinal surgery: A case report.

INTRODUCTION: The incidence of remote intracranial hemorrhage (RICH) in patients during spinal surgery is rare and the detailed mechanism remains unclear. PRESENTATION OF CASE: A 55-year-old man had undergone cervical discectomy and fusion at C5-6 and C6-7 due to herniated disc and secondary spinal canal stenosis. He had severe headache 20 h postoperatively and his drain output increased from 100 to 350 mL in the second 10 h after surgery. Computed tomography (CT) and magnetic resonance imaging (MRI) were performed and he was diagnosed with acute subarachnoid hemorrhage in the ventral medulla oblongata. The drainage tube was quickly removed. Infusion of hypertonic saline was used to reduce intracranial pressure and nimodipine prevented vasospasm around the brainstem. The patient made a gradual, satisfactory recovery with conservative treatment. DISCUSSION: The most likely pathomechanism leading to RICH is venous bleeding due to rapid leak of a large amount of cerebral spinal fluid (CSF) after spinal surgery. If the patient has a headache or neurological complaints after spinal surgery, immediate imaging is recommended to confirm the diagnosis. Treatment depends on the amount and location of intracranial hemorrhage. CONCLUSION: RICH is a serious but rare complication of spinal surgery and cerebellar hemorrhage is the most common. The most important pathomechanism leading to RICH after spinal surgery is venous bleeding due to rapid leak of a large amount of CSF. Timely CT is necessary to exclude RICH. Treatment of RICH depends on the size of the intracranial hematoma and the patient's symptoms.

Novel type of peritoneocentesis trocar-assisted distal ventriculoperitoneal shunt placement with supervision via a one-port laparoscope.

Ventriculoperitoneal shunts (VPS) are the primary treatment for hydrocephalus and are associated with a high risk of complications, specifically in patients who are obese or have abdominal adhesions or shunt revisions. The present study describes the use of a novel type of peritoneal catheter peritoneocentesis trocar insertion with the assistance of a one-port laparoscope. A total of 36 patients with hydrocephalus underwent this novel type of peritoneocentesis trocar-assisted VPS. The distal shunt catheter was placed into the right subdiaphragmatic space and the catheter was traversed through a single hole drilled through the liver falciform ligament. The duration of the laparoscopic surgery ranged from 6-18 min (mean 10.4±1.6 min). No shunt-related infections or catheter malfunctions or injuries to the intra-abdominal organs occurred. The total abdominal incision length was 1.0 cm (0.5+0.5 cm). No laparoscopy-related complications were observed during follow-up assessments. The novel approach used in the current study is very easy to perform, and this method may significantly reduce the risk of malfunction complications. The presented method also has the advantages of reduced trauma and a simpler surgery. The current study indicated that this simple, minimally invasive procedure was beneficial for patients with hydrocephalus, specifically in cases of patients with obesity, peritoneal adhesions or shunt revisions.

Overdrainage after ventriculoperitoneal shunting in a patient with a wide depressed skull bone defect: The effect of atmospheric pressure gradient.

INTRODUCTION: In patients with traumatic brain injury, an effective approach for managing refractory intracranial hypertension is wide decompressive craniectomy. Postoperative hydrocephalus is a frequent complication requiring cerebrospinal fluid (CSF) diversion. PRESENTATION OF CASE: A 50-year-old male who underwent decompressive craniectomy after traumatic brain injury. He developed hydrocephalus postoperatively, and accordingly we placed a ventriculoperitoneal shunt. However, an imbalance between the intra- and extra-cranial atmospheric pressures led to overdrainage, and he suffered cognitive disorders and extremity weakness. He remained supine for 5days to avoid the effect of gravity on CSF diversion. After 20days, we performed a cranioplasty using a titanium plate. The postoperative course was uneventful, and the patient achieved satisfactory recovery. DISCCUSION: The gravitational effect and the atmospheric pressure gradient effect are two factors associated in the ventriculoperitoneal (VP) shunt treatment of hydrocephalus for the patient who had decompressive craniectomy. These effects can be eliminated by supine bed rest and cranioplasty. CONCLUSION: We herein emphasize the efficacy of VP shunt, supine bed rest and cranioplasty in treating hydrocephalus patients who have undergone craniectomy. A flexible application of these procedures to change the gravitational effect and the atmospheric pressure gradient effect should promote a favorable outcome.