Deep Succinylproteomics of Brain Tissues from Intracerebral Hemorrhage with Inhibition of Toll-Like Receptor 4 Signaling.

It is unclear how Toll-like receptor (TLR) 4 signaling affects protein succinylation in the brain after intracerebral hemorrhage (ICH). Here, we constructed a mouse ICH model to investigate the changes in ICH-associated brain protein succinylation, following a treatment with a TLR4 antagonist, TAK242, using a high-resolution mass spectrometry-based, quantitative succinyllysine proteomics approach. We characterized the prevalence of approximately 6700 succinylation events and quantified approximately 3500 sites, highlighting 139 succinyllysine site changes in 40 pathways. Further analysis showed that TAK242 treatment induced an increase of 29 succinyllysine sites on 28 succinylated proteins and a reduction of 24 succinyllysine sites on 23 succinylated proteins in the ICH brains. TAK242 treatment induced both protein hypersuccinylations and hyposuccinylations, which were mainly located in the mitochondria and cytoplasm. GO analysis showed that TAK242 treatment-induced changes in the ICH-associated succinylated proteins were mostly located in synapses, membranes and vesicles, and enriched in many cellular functions/compartments, such as metabolism, synapse, and myelin. KEGG analysis showed that TAK242-induced hyposuccinylation was mainly linked to fatty acid metabolism, including elongation and degradation. Moreover, a combined analysis of the succinylproteomic data with previously published transcriptome data revealed that most of the differentially succinylated proteins induced by TAK242 treatment were mainly distributed throughout neurons, astrocytes, and endothelial cells, and the mRNAs of seven and three succinylated proteins were highly expressed in neurons and astrocytes, respectively. In conclusion, we revealed that several TLR4 signaling pathways affect the succinylation processes and pathways in mouse ICH brains, providing new insights on the ICH pathophysiological processes. Data are available via ProteomeXchange with identifier PXD025622.

Malignant intraventricular meningioma with craniospinal dissemination and concurrent pulmonary metastasis.

BACKGROUND: Malignant intraventricular meningiomas are quite rare and may spread along the craniospinal axis or extraneurally. However, simultaneous cerebrospinal dissemination and distal extraneural metastasis has seldom been reported. CASE PRESENTATION: A 51-year-old woman presented with recurrent anaplastic meningioma in the trigone of right lateral ventricle over a 1.5-year period. Suggested radiotherapy was refused after each operation. The patient showed a local relapse and dissemination around the previous tumoral cavity and along the spinal canal during the last recurrence. Left pulmonary metastasis was also found. She died despite multiple lesion resections. CONCLUSIONS: Malignant intraventricular meningiomas are an uncommon subset of intracranial meningiomas, and have a great potential for intraneural and extraneural metastasis. Systemic investigation for metastasis is required after surgery, especially for those without adjuvant therapies.

Upper thoracic intradural-extramedullary cavernous malformation presenting as subarachnoid hemorrhage without spinal dysfunction: a case report and review of the literature.

A 45-year-old man had subarachnoid hemorrhage (SAH) which was confirmed by lumbar puncture, since it was negative on head computed tomography. The result of neurological examination was normal. Following pan-cerebral angiography and cranial magnetic resonance imaging (MRI) failed to find out the cause of bleeding. The whole spinal MRI revealed an intradural-extramedullary mass lesion at the upper thoracic level which was consistent with cavernous malformation after surgery. When patients presented with SAH of no spinal symptoms, the diagnosis of an intradural-extramedullary cavernous malformation is challenging. A whole spinal workup should be considered in a patient with spontaneous SAH when bleeding from intracranial origin is carefully excluded.

Multiple different remote epidural hematomas after craniotomy: A case report.

BACKGROUND: Epidural hematoma is one of the common postoperative complications after craniotomy. However, multiple remote epidural hematomas in different sites, including supratentorial and infratentorial regions, are exceedingly rare. CASE SUMMARY: We present a rare case in which three remote epidural hematomas occurred after craniotomy. A 21-year-old woman was admitted with a headache for 1 mo, vomiting, and rapid vision loss for 1 wk. Brian magnetic resonance imaging indicated a right thalamic tumor. The intraoperative diagnosis was a cystic tumor, posterior cerebral artery aneurysm, and vascular malformation. The operation was successful. Unfortunately, the patient developed three extradural hematomas within 48 h. Family members consented to the first two hematoma evacuations but refused the third. CONCLUSION: More attention should be paid to this kind of rare complication. Adequate preoperative evaluation is important, especially for acute patients. Monitoring neural function and early computed tomography scanning of the brain after surgery should be highlighted.

Succinylation profiles of brain injury after intracerebral hemorrhage.

Protein posttranslational modifications (PTMs) regulate the biological processes of human diseases by genetic code expansion and cellular pathophysiology regulation; however, system-wide changes in PTM levels in the intracerebral hemorrhage (ICH) brain remain poorly understood. Succinylation refers to a major PTM during the regulation of multiple biological processes. In this study, according to the methods of quantitative succinyllysine proteomics based on high-resolution mass spectrometry, we investigated ICH-associated brain protein succinyllysine modifications and obtained 3,680 succinylated sites and quantified around 3,530 sites. Among them, 25 succinyllysine sites on 23 proteins were upregulated (hypersuccinylated), whereas 13 succinyllysine sites on 12 proteins were downregulated (hyposuccinylated) following ICH. The cell component enrichment analysis of these succinylproteins with significant changes showed that 58.3% of the hyposuccinylated proteins were observed in the mitochondria, while the hyper-succinylproteins located in mitochondria decreased in the percentage to about 35% in ICH brains with a concomitant increase in the percentage of cytoplasm to 30.4%. Further bioinformatic analysis showed that the succinylproteins were mostly mitochondria and synapse-related subcellular located and involved in many pathophysiological processes, like metabolism, synapse working, and ferroptosis. Moreover, the integrative analysis of our succinylproteomics data and previously published transcriptome data showed that the mRNAs matched by most differentially succinylated proteins were especially highly expressed in neurons, endothelial cells, and astrocytes. Our study uncovers some succinylation-affected processes and pathways in response to ICH brains and gives us novel insights into understanding pathophysiological processes of brain injury caused by ICH.

Dynamic Diffusion Tensor Imaging Reveals Structural Changes in the Bilateral Pyramidal Tracts after Brain Stem Hemorrhage in Rats.

BACKGROUND AND PURPOSE: Few studies have concentrated on pyramidal tract (PY) changes after brain stem hemorrhage (BSH). In this study, we used a diffusion tensor imaging (DTI) technique and histologic identification to investigate longitudinal PY changes on both the contralateral and ipsilateral sides after experimental BSH. METHODS: BSH was induced in 61 Sprague-Dawley rats by infusing 30 µl of autogenous tail blood into each rat's right pons. DTI and motor function examinations were performed repeatedly on days 1, 3, 7, 14, and 28 after surgery. Fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity, and radial diffusivity were measured in the bilateral PYs. The axon and myelin injury in the PY were evaluated by histologic study. RESULTS: As compared with normal controls, the bilateral PYs in rats with induced BSH showed an early decrease and a late increase in FA and an early increase and a late decrease in MD. A progressive decrease in axial diffusivity with dramatic axon loss from day 1 to day 28 after BSH was found bilaterally. The bilateral PYs showed an early increase and a late decrease in radial diffusivity. Early myelin injury and late repair were also detected pathologically in the bilateral PYs of rats with BSH. Thus, the early motor function deficits of rats with BSH began to improve on day 14 and had almost completely disappeared by day 28. CONCLUSIONS: DTI revealed dynamic changes in the bilateral PYs after BSH, which was confirmed by histologic findings and which correlated with motor function alteration. These findings support the idea that quantitative DTI can track structural changes in the bilateral PYs and that DTI may serve as a noninvasive tool to predict the prognoses of patients with BSH.

Hemorrhagic Epidermoid Cyst in Cerebellar Vermis.

Intracranial epidermoid cysts are usually located in the paramedian regions with characteristic imaging features. Intracystic hemorrhage is rarely reported with most in the cerebellopontine angle area. We described a case of hemorrhagic epidermoid cyst in cerebellar vermis. The patient was a 21-year-old male presenting with a first episode of convulsive seizure attack as the initial and sole symptom. Head computed tomography showed a mass lesion in the cerebellar vermis with high density and nodular low density in the back of the lesion. Magnetic resonance imaging revealed most of the lesion was hypointense to isointense, extremely hypointensity on T1-, T2-weighted imaging respectively. The nodule was hyperintense on both T1- and T2-weighted images. The atypical clinical presentation, location and radiological features of intracranial epidermoid cyst make accurate diagnosis quite challenging. In such cases, scrutinized histopathological examination is necessary to exclude the malignancy that may need radio/chemotherapy.