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Abstract Background Intracerebral hemorrhage (ICH) remains a serious clinical problem lacking effective treatment. Urocortin (UCN), a novel anti-inflammatory neuropeptide, protects injured cardiomyocytes and dopaminergic neurons. Our preliminary studies indicate UCN alleviates ICH-induced brain injury when administered intracerebroventricularly (ICV). The present study examines the therapeutic effect of UCN on ICH-induced neurological deficits and neuroinflammation when administered by the more convenient intraperitoneal (i.p.) route. Methods ICH was induced in male Sprague-Dawley rats by intrastriatal infusion of bacterial collagenase VII-S or autologous blood. UCN (2.5 or 25 μg/kg) was administered i.p. at 60 minutes post-ICH. Penetration of i.p. administered fluorescently labeled UCN into the striatum was examined by fluorescence microscopy. Neurological deficits were evaluated by modified neurological severity score (mNSS). Brain edema was assessed using the dry/wet method. Blood-brain barrier (BBB) disruption was assessed using the Evans blue assay. Hemorrhagic volume and lesion volume were assessed by Drabkin's method and morphometric assay, respectively. Pro-inflammatory cytokine (TNF-α, IL-1β, and IL-6) expression was evaluated by enzyme-linked immunosorbent assay (ELISA). Microglial activation and neuronal loss were evaluated by immunohistochemistry. Results Administration of UCN reduced neurological deficits from 1 to 7 days post-ICH. Surprisingly, although a higher dose (25 μg/kg, i.p.) also reduced the functional deficits associated with ICH, it is significantly less effective than the lower dose (2.5 μg/kg, i.p.). Beneficial results with the low dose of UCN included a reduction in neurological deficits from 1 to 7 days post-ICH, as well as a reduction in brain edema, BBB disruption, lesion volume, microglial activation and neuronal loss 3 days post-ICH, and suppression of TNF-α, IL-1β, and IL-6 production 1, 3 and 7 days post-ICH. Conclusion Systemic post-ICH treatment with UCN reduces striatal injury and neurological deficits, likely via suppression of microglial activation and inflammatory cytokine production. The low dose of UCN necessary and the clinically amenable peripheral route make UCN a potential candidate for development into a clinical treatment regimen.

This document is a correction notice for an article titled "Examining Transcriptomic Alterations in Rat Models of Intracerebral Hemorrhage and Severe Intracerebral Hemorrhage." The correction involves a mistake in Figure 1A, where the labels of ICH and Severe ICH were swapped. The corrected image now accurately reflects the conditions represented. The authors state that this correction does not affect the scientific conclusions of the study. The original publication has been updated to include the correction. [Extracted from the article]

Intracerebral hemorrhage (ICH) is the most lethal type of cerebral stroke without effective therapy. Although clinical trials with various surgeries have been conducted, none have improved clinical outcomes compared to the current medical management for ICH. Several ICH animal models, including autologous blood injection, collagenase injection, thrombin injection, and microballoon inflation methods, have been developed to elucidate the underlying mechanisms of ICH-induced brain injury. These models could also be used for discovering new therapy for ICH preclinically. We summarize the existing ICH animal models and the evaluation parameters used to measure the disease outcomes. We conclude that these models, resembling the different aspects of ICH pathogenesis, have their advantages and disadvantages. None of the current models closely represent the severity of ICH seen in clinical settings. More appropriate models are needed to streamline ICH's clinical outcomes and be used for validating newly developed treatment protocols. [ABSTRACT FROM AUTHOR]

Stroke is one of the leading causes of death and long-term disabilities worldwide. In addition to interruption of blood flow, inflammation is widely recognized as an important factor mediating tissue destruction in stroke. Depending on their phenotype, microglia, the main leukocytes in the CNS, are capable of either causing further tissue damage or promoting brain restoration after stroke. β2-integrins are cell adhesion molecules that are constitutively expressed on microglia. The function of β2-integrins has been investigated extensively in animal models of ischemic stroke, but their role in hemorrhagic stroke is currently poorly understood. We show in this study that dysfunction of β2-integrins is associated with improved functional outcome and decreased inflammatory cytokine expression in the brain in a mouse model of hemorrhagic stroke. Furthermore, β2-integrins affect microglial phenotype and cytokine responses in vivo. Therefore, our findings suggest that targeting β2-integrins in hemorrhagic stroke may be beneficial., (Copyright © 2024 by The American Association of Immunologists, Inc.)

Intracerebral hemorrhage (ICH) is the most lethal type of cerebral stroke without effective therapy. Although clinical trials with various surgeries have been conducted, none have improved clinical outcomes compared to the current medical management for ICH. Several ICH animal models, including autologous blood injection, collagenase injection, thrombin injection, and microballoon inflation methods, have been developed to elucidate the underlying mechanisms of ICH-induced brain injury. These models could also be used for discovering new therapy for ICH preclinically. We summarize the existing ICH animal models and the evaluation parameters used to measure the disease outcomes. We conclude that these models, resembling the different aspects of ICH pathogenesis, have their advantages and disadvantages. None of the current models closely represent the severity of ICH seen in clinical settings. More appropriate models are needed to streamline ICH's clinical outcomes and be used for validating newly developed treatment protocols., Competing Interests: There are no conflicts of interest., (Copyright: © 2022 Tzu Chi Medical Journal.)

Objective: Spontaneous intracerebral hemorrhage (ICH) accounts for 10%-15% of all strokes and causes high mortality and morbidity. In the previous study, we demonstrated that ethanol could aggravate the severity of brain injury after ICH by increasing neuroinflammation and oxidative stress. In this study, we further investigate the acute effects of ethanol on brain injury within 24 h after ICH., Materials and Methods: Totally, 66 male Sprague-Dawley rats were assigned randomly into two groups: saline pretreatment before ICH (saline + ICH), and ethanol pretreatment before ICH (ethanol + ICH). Normal saline (10 mL/kg) or ethanol (3 g/kg, in 10 mL/kg normal saline) was administered intraperitoneally 1 h before induction of experimental ICH. Bacterial collagenase VII-S (0.23 U in 1.0 μL sterile saline) was injected into the right striatum to induce ICH in the rats. We evaluated the hematoma expansion, hemodynamic parameters (heart rate and blood pressure), activated partial thromboplastin time (aPTT), prothrombin time (PT), and striatal matrix metallopeptidase 9 (MMP-9) expressions at 3, 6, 9, and 24 h after ICH., Results: The ethanol + ICH group exhibited decreased hematoma at 3 h after ICH; nevertheless, there was a larger hematoma compared with the saline + ICH group at 9 and 24 h after ICH. The ethanol + ICH group had lower blood pressure at 3, 6, and 9 h post-ICH, but both groups maintained similar heart rates after ICH. There was no significant difference in the aPTT and PT between the two groups. Incremental ethanol concentrations had no influence on collagenase VII-S activity at 120 min in vitro . MMP-9 expression was upregulated in the right striata of the ethanol + ICH group, especially at 3 and 9 h after ICH., Conclusion: Ethanol delayed hematoma formation in the first 3 h due to a hypotensive effect; however, the accelerated growth of hematomas after 9 h may be a sequela of ethanol-induced MMP-9 activation., Competing Interests: There are no conflicts of interest.

Basal ganglia hemorrhage accounts for approximately 50% of all hemorrhagic strokes. A good rat model that produces severe intrastriatal hemorrhage (ISH) mimicking human severe ISH is lacking. The present study compared the intra-striatal injection of 0.2 U with that of 0.6 U of collagenase in inducing severe ISH in rats. Three-Tesla (3T) magnetic resonance imaging (MRI) was used to evaluate brain injuries in terms of hematoma size (volume), midline shift (MLS), and brain edema. This evaluation was further substantiated by determination of behavior and neurologic functions and mortality over 56 h. The 0.2 U collagenase caused hematoma volume increases for 10.3 to 30.1 mm³, while the 0.6 U caused 36.4 to 114.8 mm³, at post-ISH 1 h to 56 h. The 0.6 U collagenase significantly increased MLS to 1.5-3.0 times greater than the 0.2 U did at all post-intracerebral hemorrhage (ICH) time points. The MLS increased dependently with hematoma expansion with high correlation coefficients, yet no mortality occurred. These two dosages, nevertheless, caused the same pattern and severity in relative apparent diffusion coefficient (rADC) changes for three regions of interest (ROIs). Both ISH models induced consistent behavior deficits. The larger dosage produced severe brain injuries as well as neurological deficits, more closely mimicking severe human ISH. Hematoma volume and MLS can be the most useful parameters for evaluating the ISH severity in the present experimental model. The larger dosage, therefore, would be useful for investigating the pathophysiology of the severer ISH in the striatum. This may be applied for evaluating potential therapeutic strategies and outcomes in the future., Competing Interests: The authors declare that there are no conflicts of interests.

Granulocyte-colony stimulating factor (G-CSF) protects brain from ischemic/reperfusion (I/R) injury, and inhibition of nitric oxide (NO) synthases partially reduces G-CSF protection. We thus further investigated the effects of G-CSF on ischemia-induced NO production and its consequence on regional cerebral blood flow (rCBF) and neurological deficit. Endothelin-1 (ET-1) microinfused above middle cerebral artery caused a rapid reduction of rCBF (ischemia) which lasted for 30 minutes and was followed by a gradual recovery of blood flow (reperfusion) within the striatal region. Regional NO concentration increased rapidly (NO surge) during ischemia and recovered soon to the baseline. G-CSF increased rCBF resulting in shorter ischemic duration and an earlier onset of reperfusion. The enhancement of the ischemia-induced NO by G-CSF accompanied by elevation of phospho-Akt and phospho-eNOS was noted, suggesting an activation of Akt/eNOS. I/R-induced infarct volume and neurological deficits were also reduced by G-CSF treatment. Inhibition of NO synthesis by L-N(G)-Nitroarginine Methyl Ester (L-NAME) significantly reduced the effects of G-CSF on rCBF, NO surge, infarct volume, and neurological deficits. We conclude that G-CSF increases rCBF through a NO surge mediated by Akt/eNOS, which partially contributes to the beneficial effect of G-CSF on brain I/R injury.