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Grade IV: Section of the fourt ventricle with the choroidal plexus and diffuse blood clot visible within the ventricular cavity (long blue arrow pointing at the coroidal pexus and short blue arrow pointing at the blood clot within the ventricular cavity of the fourth ventricle). https://doi.org/10.1371/journal.pone.0227349.g004
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Objective
The amount of extravasated blood is an established surrogate marker for subarachnoid hemorrhage (SAH) severity, which varies in different experimental SAH (eSAH) models. A comprehensive eSAH grading system would allow a more reliable correlation of outcome parameters with SAH severity. The aim of this study was to define a severity score...
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Background
The subarachnoid space is continuous with the perivascular compartment in the central nervous system. However, whether the topography and severity of enlarged perivascular spaces (EPVS) correlates with spontaneous subarachnoid hemorrhage (SAH) remains unknown. Based on the underlying arteriopathy distributions, we hypothesized that EPVS...
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Citations
... The cumulative scores from all tests were then aggregated to derive a final ROB score. Subarachnoid hemorrhage severity criteria of ROB score: severe (3-6), moderate (7-10), and mild (11)(12)(13)(14)(15). ...
... Moreover, certain assessment protocols necessitate the euthanasia of animals and subsequent autopsy to define the severity of neurological deficits. While such approaches may yield valuable data, they are inherently invasive and limit the ability to monitor long-term recovery 8,14 . ...
The Circle of Willis perforation (cWp) mouse model is a key tool in subarachnoid hemorrhage (SAH) research; however, inconsistent bleeding volumes can challenge experimental reliability. To address this issue, we introduced the ROB Scoring System, a novel protocol integrating Rotarod Tests (RT), Open-field Tests (OT) video analysis, and daily Body Weight Loss (BWL) monitoring to precisely categorize SAH severity. Forty C57BL/6 mice underwent cWp SAH induction, categorized by ROB into severity subgroups (severe, moderate, mild). Validation compared ROB trends in subgroups, and ROB outcomes with autopsy results on postoperative days three and seven for acute and sub-acute evaluations. Mortality rates were analyzed via the survival log-rank test, revealing a significant difference among SAH subgroups (P < 0.05). Strong correlations between ROB grades and autopsy findings underscored its precision. Notably, the severe group exhibited 100% mortality within 4 days post SAH onset. Single parameters (RT, OT, BWL) were insufficient for distinguishing SAH severity levels. The ROB score represents a significant advancement, offering an objective method for precise categorization and addressing inherent bleeding variations in the cWp SAH model. This standardized protocol enhances the reliability and effectiveness of the SAH translational research, providing a valuable tool for future investigations into this critical area.
... The sham group underwent identical procedures without the vascular perforation. The severity of SAH was blindly assessed at the time of sacrifice according to the previously described grading system [13]. Rats displaying SAH severity scores between 8-13 were used for further experiments [14]. ...
White matter damage (WMD), one of the research hotspots of subarachnoid hemorrhage (SAH), mainly manifests itself as myelin injury and oligodendrocyte differentiation disorder after SAH, although the specific mechanism remains unclear. Dexamethasone-induced Ras-related protein 1(Dexras1) has been reported to be involved in nervous system damage in autoimmune encephalitis and multiple sclerosis. However, whether Dexras1 participates in dysdifferentiation of oligodendrocytes and myelin injury after SAH has yet to be examined, which is the reason for creating the research content of this article. Here, intracerebroventricular lentiviral administration was used to modulate Dexras1 levels in order to determine its functional influence on neurological injury after SAH. Immunofluorescence, transmission electron microscopy, and Western blotting methods, were used to investigate the effects of Dexras1 on demyelination, glial cell activation, and differentiation of oligodendrocyte progenitor cells (OPCs) after SAH. Primary rat brain neurons were treated with oxyhemoglobin to verify the association between Dexras1 and cAMP-CREB. The results showed that Dexras1 levels were significantly increased upon in vivo SAH model, accompanied by OPC differentiation disturbances and myelin injury. Dexras1 overexpression significantly worsened OPC dysdifferentiation and myelin injury after SAH. In contrast, Dexras1 knockdown ameliorated myelin injury, OPC dysdifferentiation, and glial cell activation. Further research of the underlying mechanism discovered that the cAMP-CREB pathway was inhibited after Dexras1 overexpression in the in vitro model of SAH. This study is the first to confirm that Dexras1 induced oligodendrocyte dysdifferentiation and myelin injury after SAH by inhibiting the cAMP-CREB pathway. This present research may reveal novel therapeutic targets for the amelioration of brain injury and neurological dysfunction after SAH.
... The animals were given an overall score between 0 and 18 after summation of all scores. After evaluation of the neurological scores, the SAH severity was blindly assessed according to the previously described grading scale at the time of sacri ce [24,25]. These scores also ranged from 0 to 18. Animals with a < 5 score were eliminated due to low SAH grade [26]. ...
Background
White matter damage (WMD), different from the widely studied neuronal death, is also involved in neurological dysfunction after subarachnoid hemorrhage (SAH) although the specific mechanism is not yet known. Dexras1 (RASD1) has been reported to be involved in nervous system damage in autoimmune encephalitis and multiple sclerosis; however, there is no information on whether Dexras1 participates in WMD after SAH. We hypothesized that Dexras1 participates in oligodendrocyte precursor cell (OPC) differentiation in WMD after SAH.Methods
Intracerebroventricular lentiviral administration was used to modulate Dexras1 levels to determine its functional influence on neurological injuries after SAH. Immunofluorescence, transmission electron microscopy, and Western blotting were used to investigate the effects of Dexras1 on demyelination, glial cell activation and differentiation of OPCs after SAH. Primary rat brain neurons were treated with oxyhemoglobin to elucidate the association between Dexras1 and cAMP-CREB.ResultsDexras1 levels were significantly increased after SAH, accompanied by clear neurological deficits, glial cell activation, OPC differentiation disorders, and myelin injury. Dexras1 overexpression significantly worsened OPC dysdifferentiation and myelin injury after SAH, which were accompanied by increased glial cell activation and levels of inflammatory factors. In contrast, Dexras1 knockdown ameliorated demyelination, oligodendrocyte differentiation disorders, and glial cell activation. cAMP acted as an upstream agonist of CREB, with decreased TNF-α and IL-1β levels after SAH. However, the cAMP-CREB pathway was inhibited after Dexras1 overexpression.ConclusionDexras1 induced oligodendrocyte dysdifferentiation after SAH and regulated glial cell activation through suppression of the cAMP-CREB pathway. This research highlights a novel direction for the improvement of neurological dysfunction after SAH.
... Previous studies were able to demonstrate that this specific model facilitates the reliable induction of severe SAH with a high incidence of vasospasm, making it specifically suitable for the evaluation of this phenomenon. 17,18,31 In the present study, we found an overall high incidence of cerebral vasospasm on day 2 (65%) as well as on day 5 (86%), which again reflects the aforementioned benefits of this experimental SAH-model. Considering vasospasm severity, expectedly, severe vasospasm was seen more often on day 5 (49%) compared to day 2 (21%). ...
Transcranial direct current stimulation (tDCS) has been shown to induce changes in cortical excitability and perfusion in a rat ischemic stroke model. Since perfusion disturbances are a common phenomenon, not only in ischemic but also in hemorrhagic stroke, tDCS might have a possible beneficial effect on cerebral perfusion in hemorrhagic stroke as well. We applied tDCS in a rat model of subarachnoid hemorrhage (SAH) and evaluated its impact on vasospasm. SAH was induced using the double-hemorrhage rat model. TDCS was applied on day 3 and 4. For vasospasm assessment magnetic resonance angiography was performed on day 1, day 2 and day 5. A total of 147 rats were operated, whereat 72 rats died before day 5 and 75 rats survived the whole experiment and could be analyzed. The cathodal group consisted of 26 rats, the anodal group included 24 rats. Thirteen rats served as controls without tDCS, and twelve rats underwent a sham operation. The cathodal group revealed the lowest incidence of new vasospasm on day 5 ( p = 0.01), and the lowest mean number of vasospastic vessels per rat ( p = 0.02). TDCS influences the vasospasm incidence in an SAH-model in rats, where cathodal-tDCS was associated with a lower vasospasm incidence and severity.
The Circle of Willis perforation (cWp) mouse model is a key tool in subarachnoid hemorrhage (SAH) research; however, inconsistent bleeding volumes can challenge experimental reliability. To address this issue, we introduced the ROB Scoring System, a novel protocol integrating Rotarod Tests (RT), Open-field Tests (OT) video analysis, and daily Body Weight Loss (BWL) monitoring to precisely categorize SAH severity. Forty C57BL/6 mice underwent cWp induction, categorized by ROB into severity subgroups (severe, moderate, mild). Validation compared ROB outcomes with autopsy results on postoperative days 3 and 7 for acute and sub-acute evaluations. Mortality rates were analyzed via the survival log-rank test, revealing a significant difference among severity groups (P < 0.0001). Strong correlations between ROB grades and autopsy findings underscored its precision. Notably, the severe group exhibited 100% mortality within 4 days post-SAH onset. Individual parameters (RT, OT, BWL) were insufficient for distinguishing SAH severity levels. The ROB Scoring System represents a significant advancement, offering precise categorization and addressing inherent bleeding variations in the cWp mouse model. This standardized protocol enhances the reliability and effectiveness of SAH research, providing a valuable tool for future investigations into this critical.
