Tianjie Zhang, Fan Xia, Yingfeng Wan, Guohua Xi, Hua Ya, Richard F Keep
{"title":"Complement Inhibition Reduces Early Erythrolysis, Attenuates Brain Injury, Hydrocephalus, and Iron Accumulation after Intraventricular Hemorrhage in Aged Rats.","authors":"Tianjie Zhang, Fan Xia, Yingfeng Wan, Guohua Xi, Hua Ya, Richard F Keep","doi":"10.1007/s12975-024-01273-6","DOIUrl":"https://doi.org/10.1007/s12975-024-01273-6","url":null,"abstract":"<p><p>Blood components released by erythrolysis play an important role in secondary brain injury and posthemorrhagic hydrocephalus (PHH) after intraventricular hemorrhage (IVH). The current study examined the impact of N-acetylheparin (NAH), a complement inhibitor, on early erythrolysis, PHH and iron accumulation in aged rats following IVH. This study, on 18-months-old male Fischer 344 rats, was in 3 parts. First, rats had an intracerebroventricular injection of autologous blood (IVH) mixed with NAH or saline, or saline alone. After MRI at four hours, Western blot and immunohistochemistry examined complement activation and electron microscopy choroid plexus and periventricular damage. Second, rats had an IVH with NAH or vehicle, or saline. Rats underwent serial MRI at 4 h and 1 day to assess ventricular volume and erythrolysis. Immunohistochemistry and H&E staining examined secondary brain injury. Third, rats had an IVH with NAH or vehicle. Serial MRIs on day 1 and 28 assessed ventricular volume and iron accumulation. H&E staining and immunofluorescence evaluated choroid plexus phagocytes. Complement activation was found 4 h after IVH, and co-injection of NAH inhibited that activation. NAH administration attenuated erythrolysis, reduced ventricular volume, alleviated periventricular and choroid plexus injury at 4 h and 1 day after IVH. NAH decreased iron accumulation, the number of choroid plexus phagocytes, and attenuated hydrocephalus at 28 days after IVH. Inhibiting complement can reduce early erythrolysis, attenuates hydrocephalus and iron accumulation after IVH in aged animals.</p>","PeriodicalId":23237,"journal":{"name":"Translational Stroke Research","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2024-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141470963","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"HDAC9 Deficiency Upregulates cGMP-dependent Kinase II to Mitigate Neuronal Apoptosis in Ischemic Stroke.","authors":"Haoran Lin, Yun Bei, Zexu Shen, Taofeng Wei, Yuyang Ge, Lingyan Yu, Huimin Xu, Wei He, Yunjian Dai, Difei Yao, Haibin Dai","doi":"10.1007/s12975-024-01272-7","DOIUrl":"https://doi.org/10.1007/s12975-024-01272-7","url":null,"abstract":"<p><p>Histone deacetylase 9 (HDAC9) is implicated in ischemic stroke by genome-wide association studies. We conducted a series of experiments using a mouse model of ischemic stroke (middle cerebral artery occlusion followed by reperfusion) to examine the potential role of HDAC9. Briefly, HDAC9 was upregulated in the penumbra. Deletion of HDAC9 from neurons reduced infarction volume, inhibited neuronal apoptosis in the penumbra, and improved neurological outcomes. HDAC9 knockout from neurons in the penumbra upregulated cGMP-dependent kinase II (cGK II), blocking which abrogated the protective effects of HDAC9 deletion. Mechanistically, HDAC9 interacts with the transcription factor MEF2, thereby inhibiting MEF2's binding to the promoter region of the cGK II gene, which results in the suppression of cGK II expression. Inhibiting the interaction between HDAC9 and MEF2 by BML210 upregulated cGK II and attenuated ischemic injury in mice. These results encourage targeting the HDAC9-MEF2 interaction in developing novel therapy against ischemic stroke.</p>","PeriodicalId":23237,"journal":{"name":"Translational Stroke Research","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2024-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141470964","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Cerebral [<sup>18</sup>F]AIF-FAPI-42-Based PET Imaging of Fibroblast Activation Protein for Non-invasive Quantification of Fibrosis After Ischemic Stroke.","authors":"Peipei Tang, Yang Liu, Simin Peng, Zhikai Cai, Ganghua Tang, Zhou Zhou, Kongzhen Hu, Yuhua Zhong","doi":"10.1007/s12975-024-01269-2","DOIUrl":"https://doi.org/10.1007/s12975-024-01269-2","url":null,"abstract":"<p><p>The development of fibrosis after injury to the brain or spinal cord limits the regeneration of the central nervous system in adult mammals. However, the extent of fibrosis in the injured brain has not been systematically investigated in mammals in vivo. This study aimed to assess whether [<sup>18</sup>F]AlF-FAPI-42-based cerebral positron emission tomography (PET) can be utilized to assess the extent of fibrosis in ischemic regions of the brain in vivo. Sprague-Dawley rats underwent permanent occlusion of the right middle cerebral artery (MCAO). On days 3, 7, 14, and 21 after MCAO, the uptake of [<sup>18</sup>F]AlF-FAPI-42 in the ischemic region of the brain in the MCAO groups surpassed that in the control group (day 0). The specific expression of fibroblast activation protein-α (FAP) in ischemic regions of the brain was also confirmed in immunohistofluorescence experiments in vitro. [<sup>18</sup>F]AlF-FAPI-42 intensity correlated with the density of collagen deposition in the ischemic hemisphere (p < 0.001). [<sup>18</sup>F]AlF-FAPI-42 PET/CT imaging demonstrated a specific uptake of radioactivity in the infarcted area in an ischemic stroke patient. PET imaging by using [<sup>18</sup>F]AlF-FAPI-42 offers a promising non-invasive method for monitoring the progression of cerebral fibrosis caused by ischemic stroke and may facilitate the clinical management of stroke patients. Trial registration: chictr.org.cn ChiCTR2200059004. Registered April 22, 2022.</p>","PeriodicalId":23237,"journal":{"name":"Translational Stroke Research","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2024-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141470962","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Anil K Chokkalla, Vijay Arruri, Suresh L Mehta, Raghu Vemuganti
{"title":"Loss of Epitranscriptomic Modification N<sup>6</sup>-Methyladenosine (m<sup>6</sup>A) Reader YTHDF1 Exacerbates Ischemic Brain Injury in a Sexually Dimorphic Manner.","authors":"Anil K Chokkalla, Vijay Arruri, Suresh L Mehta, Raghu Vemuganti","doi":"10.1007/s12975-024-01267-4","DOIUrl":"https://doi.org/10.1007/s12975-024-01267-4","url":null,"abstract":"<p><p>N<sup>6</sup>-Methyladenosine (m<sup>6</sup>A) is a neuronal-enriched, reversible post-transcriptional modification that regulates RNA metabolism. The m<sup>6</sup>A-modified RNAs recruit various m<sup>6</sup>A-binding proteins that act as readers. Differential m<sup>6</sup>A methylation patterns are implicated in ischemic brain damage, yet the precise role of m<sup>6</sup>A readers in propagating post-stroke m<sup>6</sup>A signaling remains unclear. We presently evaluated the functional significance of the brain-enriched m<sup>6</sup>A reader YTHDF1, in post-stroke pathophysiology. Focal cerebral ischemia significantly increased YTHDF1 mRNA and protein expression in adult mice of both sexes. YTHDF1<sup>-/-</sup> male, but not female, mice subjected to transient middle cerebral artery occlusion (MCAO) showed worsened motor function recovery and increased infarction compared to sex-matched YTHDF1<sup>+/+</sup> mice. YTHDF1<sup>-/-</sup> male, but not female, mice subjected to transient MCAO also showed significantly perturbed expression of genes related to inflammation, and increased infiltration of peripheral immune cells into the peri-infarct cortex, compared with sex-matched YTHDF1<sup>+/+</sup> mice. Thus, this study demonstrates a sexual dimorphism of YTHDF1 in regulating post-ischemic inflammation and pathophysiology. Hence, post-stroke epitranscriptomic regulation might be sex-dependent.</p>","PeriodicalId":23237,"journal":{"name":"Translational Stroke Research","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2024-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141311820","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Xing Wang, Dingke Wen, Fan Xia, Mei Fang, Jun Zheng, Chao You, Lu Ma
{"title":"Single-Cell Transcriptomics Revealed White Matter Repair Following Subarachnoid Hemorrhage.","authors":"Xing Wang, Dingke Wen, Fan Xia, Mei Fang, Jun Zheng, Chao You, Lu Ma","doi":"10.1007/s12975-024-01265-6","DOIUrl":"https://doi.org/10.1007/s12975-024-01265-6","url":null,"abstract":"<p><p>Existing research indicates the potential for white matter injury repair during the subacute phase following subarachnoid hemorrhage (SAH). However, elucidating the role of brain cell subpopulations in the acute and subacute phases of SAH pathogenesis remains challenging due to the cellular heterogeneity of the central nervous system. In this study, single-cell RNA sequencing was conducted on SAH model mice to delineate distinct cell populations. Gene Set Enrichment Analysis was performed to identify involved pathways, and cellular interactions were explored using the CellChat package in R software. Validation of the findings involved a comprehensive approach, including magnetic resonance imaging, immunofluorescence double staining, and Western blot analyses. This study identified ten major brain clusters with cell type-specific gene expression patterns. Notably, we observed infiltration and clonal expansion of reparative microglia in white matter-enriched regions during the subacute stage after SAH. Additionally, microglia-associated pleiotrophin (PTN) was identified as having a role in mediating the regulation of oligodendrocyte precursor cells (OPCs) in SAH model mice, implicating the activation of the mTOR signaling pathway. These findings emphasize the vital role of microglia-OPC interactions might occur via the PTN pathway, potentially contributing to white matter repair during the subacute phase after SAH. Our analysis revealed precise transcriptional changes in the acute and subacute phases after SAH, offering insights into the mechanism of SAH and for the development of drugs that target-specific cell subtypes.</p>","PeriodicalId":23237,"journal":{"name":"Translational Stroke Research","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2024-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141301663","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Sricharan S Veeturi, Samuel Hall, Soichiro Fujimura, Mahmud Mossa-Basha, Elena Sagues, Edgar A Samaniego, Vincent M Tutino
{"title":"Imaging of Intracranial Aneurysms: A Review of Standard and Advanced Imaging Techniques.","authors":"Sricharan S Veeturi, Samuel Hall, Soichiro Fujimura, Mahmud Mossa-Basha, Elena Sagues, Edgar A Samaniego, Vincent M Tutino","doi":"10.1007/s12975-024-01261-w","DOIUrl":"https://doi.org/10.1007/s12975-024-01261-w","url":null,"abstract":"<p><p>The treatment of intracranial aneurysms is dictated by its risk of rupture in the future. Several clinical and radiological risk factors for aneurysm rupture have been described and incorporated into prediction models. Despite the recent technological advancements in aneurysm imaging, linear length and visible irregularity with a bleb are the only radiological measure used in clinical prediction models. The purpose of this article is to summarize both the standard imaging techniques, including their limitations, and the advanced techniques being used experimentally to image aneurysms. It is expected that as our understanding of advanced techniques improves, and their ability to predict clinical events is demonstrated, they become an increasingly routine part of aneurysm assessment. It is important that neurovascular specialists understand the spectrum of imaging techniques available.</p>","PeriodicalId":23237,"journal":{"name":"Translational Stroke Research","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2024-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141296743","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
William M Armstead, Hugh Hekierski, Philip Pastor, Serge Yarovoi, Abd Al-Roof Higazi, Douglas B Cines
{"title":"Retraction Note: Release of IL-6 After Stroke Contributes to Impaired Cerebral Autoregulation and Hippocampal Neuronal Necrosis Through NMDA Receptor Activation and Upregulation of ET-1 and JNK.","authors":"William M Armstead, Hugh Hekierski, Philip Pastor, Serge Yarovoi, Abd Al-Roof Higazi, Douglas B Cines","doi":"10.1007/s12975-024-01264-7","DOIUrl":"https://doi.org/10.1007/s12975-024-01264-7","url":null,"abstract":"","PeriodicalId":23237,"journal":{"name":"Translational Stroke Research","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2024-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141261808","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Abdulkarim Alshammari, Bindu Pillai, Pradip Kamat, Timothy W Jones, Asamoah Bosomtwi, Mohammad Badruzzaman Khan, David C Hess, Weiguo Li, Payaningal R Somanath, Mohammed A Sayed, Adviye Ergul, Susan C Fagan
{"title":"Correction to: Angiotensin II Type 2 Receptor Agonism Alleviates Progressive Post‑stroke Cognitive Impairment in Aged Spontaneously Hypertensive Rats.","authors":"Abdulkarim Alshammari, Bindu Pillai, Pradip Kamat, Timothy W Jones, Asamoah Bosomtwi, Mohammad Badruzzaman Khan, David C Hess, Weiguo Li, Payaningal R Somanath, Mohammed A Sayed, Adviye Ergul, Susan C Fagan","doi":"10.1007/s12975-024-01263-8","DOIUrl":"https://doi.org/10.1007/s12975-024-01263-8","url":null,"abstract":"","PeriodicalId":23237,"journal":{"name":"Translational Stroke Research","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2024-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141248585","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mark Cwajna, Abdelrahman M Hamouda, Nicholas Kendall, Sherief Ghozy, Benjamin D Elder, David F Kallmes
{"title":"Reporting Compliance and Factors Influencing Timeliness of Stroke-Related Trial Results on ClinicalTrials.gov.","authors":"Mark Cwajna, Abdelrahman M Hamouda, Nicholas Kendall, Sherief Ghozy, Benjamin D Elder, David F Kallmes","doi":"10.1007/s12975-024-01260-x","DOIUrl":"https://doi.org/10.1007/s12975-024-01260-x","url":null,"abstract":"<p><p>Since 2007, research groups are mandated by the Food and Drug Administration Amendments Act (FDAAA) to report clinical trial findings to ClinicalTrials.gov within 12 months of trial completion. This observational study aims to analyze compliance data of stroke-related randomized controlled trials subject to these mandates. Using a previously published algorithm, we identified clinical trials likely to be required to adhere to FDAAA mandates (highly likely applicable clinical trials, or HLACTs) from January 2008 to February 2023. We assessed the proportion of studies that reported results within 12 months of trial completion, as well as those that reported at any point within 5 years. Additionally, we utilized Kaplan-Meier and regression analysis to explore factors associated with on-time reporting. Among 357 stroke-related HLACTs on ClinicalTrials.gov that were terminated or completed between January 1, 2008, and February 1, 2023, 59 (16.5%) reported results within 12 months, while 320 (89.6%) reported results within 5 years. Median reporting times for industry funded, other government or academic institution funded, and National Institute of Health (NIH) funded studies were 18.5 months, 22 months, and 22.5 months, respectively. Open-label studies were less likely to report results by 12 months compared to double-blinded studies (p = 0.002). Biological trials exhibited a lower probability of reporting within 5 years compared to device and/or drug trials (p = 0.007). Clinical trial registries and FDAAA mandates aim to promote accountability and transparency in health sciences research. However, regardless of their funding source, only a minority of stroke-related randomized controlled trials comply with FDAAA's 12-month result reporting mandate.</p>","PeriodicalId":23237,"journal":{"name":"Translational Stroke Research","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2024-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141237652","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Colton J Smith, Christina P Rossitto, Michael Manhart, Imke Fuhrmann, Julie DiNitto, Turner Baker, Muhammad Ali, Marily Sarmiento, J Mocco, Christopher P Kellner
{"title":"Minimally Invasive Intracerebral Hemorrhage Evacuation Improves Pericavity Cerebral Blood Volume.","authors":"Colton J Smith, Christina P Rossitto, Michael Manhart, Imke Fuhrmann, Julie DiNitto, Turner Baker, Muhammad Ali, Marily Sarmiento, J Mocco, Christopher P Kellner","doi":"10.1007/s12975-023-01155-3","DOIUrl":"10.1007/s12975-023-01155-3","url":null,"abstract":"<p><p>Cerebral blood volume mapping can characterize hemodynamic changes within brain tissue, particularly after stroke. This study aims to quantify blood volume changes in the perihematomal parenchyma and pericavity parenchyma after minimally invasive intracerebral hemorrhage evacuation (MIS for ICH). Thirty-two patients underwent MIS for ICH with pre- and post-operative CT imaging and intraoperative perfusion imaging (DynaCT PBV Neuro, Artis Q, Siemens). The pre-operative and post-operative CT scans were segmented using ITK-SNAP software to calculate hematoma volumes and to delineate the pericavity tissue. Helical CT segmentations were registered to cone beam CT data using elastix software. Mean blood volumes were computed inside subvolumes by dilating the segmentations at increasing distances from the lesion. Pre-operative perihematomal blood volumes and post-operative pericavity blood volumes (PBV) were compared. In 27 patients with complete imaging, post-operative PBV significantly increased within the 6-mm pericavity region after MIS for ICH. The mean relative PBV increased by 21.6 and 9.1% at 3 mm and 6 mm, respectively (P = 0.001 and 0.016, respectively). At the 9-mm pericavity region, there was a 2.83% increase in mean relative PBV, though no longer statistically significant. PBV analysis demonstrated a significant increase in pericavity cerebral blood volume after minimally invasive ICH evacuation to a distance of 6 mm from the border of the lesion.</p>","PeriodicalId":23237,"journal":{"name":"Translational Stroke Research","volume":" ","pages":"599-605"},"PeriodicalIF":6.9,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9470163","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}