Diagnosis of Delayed Cerebral Ischemia in Patients with Aneurysmal Subarachnoid Hemorrhage and Triggers for Intervention

Neurocritical Care, Journal Year: 2023, Volume and Issue: 39(2), P. 311 - 319

Published: Aug. 3, 2023

Abstract Introduction Delayed cerebral ischemia (DCI) is a major determinant for poor neurological outcome after aneurysmal subarachnoid hemorrhage (aSAH). Detection and treatment of DCI key component in the neurocritical care patients with aSAH initial aneurysm repair. Methods Narrative review literature. Results Over past 2 decades, there has been paradigm shift away from macrovascular (angiographic) vasospasm as main diagnostic therapeutic target. Instead, pathophysiology hypothesized to derive several proischemic pathomechanisms. Clinical examination remains most reliable means monitoring DCI, but its value limited comatose patients. In such patients, usually based on numerous neurophysiological and/or radiological modalities. Catheter angiography gold standard detection spasm. Computed tomography (CT) increasingly used instead catheter because it less invasive may be combined CT perfusion imaging. permits semiquantitative blood flow measurements, including evaluation microcirculation. It prediction, early detection, diagnosis yet-to-prove benefit clinical when screening modality. Transcranial Doppler considered an additional noninvasive tool velocities middle artery, accuracy other arteries. Continuous electroencephalography enables signs at reversible stage prior manifestation. However, widespread use still required infrastructure expertise data interpretation. Near-infrared spectroscopy, continuous modality dynamics, shown conflicting results needs further validation. Monitoring techniques beyond examinations help especially these are their nature restriction measurements focal brain areas. Conclusion The current literature underscores need incorporating existing modalities developing new methods evaluate perfusion, metabolism, overall function more accurately globally.

Language: Английский

---

Haptoglobin Attenuates Cerebrospinal Fluid Hemoglobin-Induced Neurological Deterioration in Sheep

Translational Stroke Research, Journal Year: 2024, Volume and Issue: unknown

Published: April 23, 2024

Secondary brain injury (SBI) occurs with a lag of several days post-bleeding in patients aneurysmal subarachnoid hemorrhage (aSAH) and is strong contributor to mortality long-term morbidity. aSAH-SBI coincides cell-free hemoglobin (Hb) release into the cerebrospinal fluid. This temporal association convincing pathophysiological concepts suggest that CSF-Hb could be targetable trigger SBI. However, sparse experimental evidence for Hb's neurotoxicity vivo defines significant research gap clinical translation. We modeled exposure observed aSAH conscious sheep, which allowed us assess neurological functions gyrencephalic species. Twelve animals were randomly assigned 3-day bi-daily intracerebroventricular (ICV) injections either Hb or combined high-affinity scavenger protein haptoglobin (Hb-Hp, CSL888). Repeated CSF sampling confirmed clinically relevant concentrations. prolonged over 3 resulted disturbed movement activity, reduced food intake, impaired observational neuroscores. The Hb-induced neurotoxic effects significantly attenuated when was administered equimolar haptoglobin. Preterminal magnetic resonance imaging (MRI) showed no CSF-Hb-specific structural alterations. In both groups, histology demonstrated an inflammatory response revealed enhanced perivascular histiocytic infiltrates Hb-Hp group, indicative adaptive mechanisms. Heme iron deposition comparable, suggesting comparable clearance efficiency Hb-haptoglobin complexes from intracranial compartment. identified phenotype toxicity rather due neurovascular dysfunction than injury. Haptoglobin effective at attenuating CSF-Hb-induced deterioration, supporting its therapeutic potential.

Language: Английский

---

4-Hydroxyderricin attenuates ischemic brain injury and neuroinflammation by upregulating haptoglobin expression in microglia

Phytomedicine, Journal Year: 2025, Volume and Issue: unknown, P. 156649 - 156649

Published: March 1, 2025

Language: Английский

---

Red Blood Cells in the Cerebrospinal Fluid Compartment After Subarachnoid Haemorrhage: Significance and Emerging Therapeutic Strategies

Translational Stroke Research, Journal Year: 2024, Volume and Issue: unknown

Published: Feb. 29, 2024

Subarachnoid haemorrhage (SAH) is a subtype of stroke that predominantly impacts younger individuals. It associated with high mortality rates and can cause long-term disabilities. This review examines the contribution initial blood load dynamics clot clearance to pathophysiology SAH risk adverse outcomes. These outcomes include hydrocephalus delayed cerebral ischaemia (DCI), particular focus on impact located in cisternal spaces, as opposed ventricular blood, development DCI. The literature described underscores prognostic value haematoma characteristics, such volume, density, anatomical location. limitations traditional radiographic grading systems are discussed, compared more accurate volumetric quantification techniques for predicting patient prognosis. Further, significance red cells (RBCs) their breakdown products secondary brain injury after explored. presents novel interventions designed accelerate or mitigate effects toxic byproducts released from erythrolysis cerebrospinal fluid following SAH. In conclusion, this offers deeper insights into complex discusses potential pathways available advancing its management.

Language: Английский

---

All Three Supersystems—Nervous, Vascular, and Immune—Contribute to the Cortical Infarcts After Subarachnoid Hemorrhage

Translational Stroke Research, Journal Year: 2024, Volume and Issue: unknown

Published: April 30, 2024

The recently published DISCHARGE-1 trial supports the observations of earlier autopsy and neuroimaging studies that almost 70% all focal brain damage after aneurysmal subarachnoid hemorrhage are anemic infarcts cortex, often also affecting white matter immediately below. not limited by usual vascular territories. About two-fifths ischemic occurs within ~ 48 h; remaining three-fifths delayed (within 3 weeks). Using neuromonitoring technology in combination with longitudinal neuroimaging, entire sequence both early cortical infarct development has been recorded patients. Characteristically, caused acute severe vasospastic events, so-called spreading ischemia, triggered spontaneously occurring depolarization. In locations where a depolarization passes through, cerebral blood flow can drastically drop few seconds remain suppressed for minutes or even hours, followed high-amplitude, sustained hyperemia. depolarization, neurons lead event, other cells neurovascular unit (endothelium, smooth muscle, pericytes, astrocytes, microglia, oligodendrocytes) follow. However, dysregulation three supersystems-nervous, vascular, immune-is very likely involved dysfunction underlying ischemia. It is assumed blood, which lies directly on cortex enters parenchyma via glymphatic channels, triggers these dysregulations. This review discusses neuroglial, neurovascular, neuroimmunological dysregulations context ischemia as critical elements pathogenesis hemorrhage.

Language: Английский

---

Hemorrhage-activated NRF2 in tumor-associated macrophages drives cancer growth, invasion, and immunotherapy resistance

Journal of Clinical Investigation, Journal Year: 2023, Volume and Issue: 134(3)

Published: Dec. 7, 2023

Microscopic hemorrhage is a common aspect of cancers, yet its potential role as an independent factor influencing both cancer progression and therapeutic response largely ignored. Recognizing the essential function macrophages in red blood cell disposal, we explored pathway that connects intratumoral with formation cancer-promoting tumor-associated (TAMs). Using spatial transcriptomics, found NRF2-activated myeloid cells possessing characteristics procancerous TAMs tend to cluster peri-necrotic hemorrhagic tumor regions. These resembled anti-inflammatory erythrophagocytic macrophages. We identified heme, metabolite, pivotal microenvironmental steering toward protumorigenic activities. Single-cell RNA-seq functional assays 3D culture spheroids revealed how elevated intracellular heme signals via transcription NRF2 induce TAMs. stabilized epithelial-mesenchymal transition, enhancing invasiveness metastatic potential. Additionally, exhibited resistance reprogramming by IFNγ anti-CD40 antibodies, reducing their tumoricidal capacity. Furthermore, MC38 colon adenocarcinoma-bearing mice constitutively activated leukocytes were resistant immunotherapy. Overall, our findings emphasize hemorrhage-activated driver progression, suggesting targeting this could offer new strategies enhance immunity overcome therapy resistance.

Language: Английский

---

Hypoxia-Induced Myocardial Hypertrophy Companies with Apoptosis Enhancement and p38-MAPK Pathway Activation

High Altitude Medicine & Biology, Journal Year: 2024, Volume and Issue: 25(3), P. 186 - 196

Published: April 22, 2024

Li, Xiaoxu, Zhijun Pu, Gang Xu, Yidong Yang, Yu Cui, Xiaoying Zhou, Chenyuan Wang, Zhifeng Zhong, Simin Jun Yin, Fabo Shan, Chengzhong Li Jiao, Dewei Chen, and Jian Huang. Hypoxia-induced myocardial hypertrophy companies with apoptosis enhancement p38-MAPK pathway activation. High Alt Med Biol. 00:00–00, 2024.

Language: Английский

---

Acute evacuation of 54 intracerebral hematomas (aICH) during the microsurgical clipping of a ruptured middle cerebral artery bifurcation aneurysm—illustration of the individual clinical courses and outcomes with a serial brain CT/MRI panel until 12 months

Acta Neurochirurgica, Journal Year: 2024, Volume and Issue: 166(1)

Published: Jan. 17, 2024

Abstract Purpose In aneurysmal intracerebral hemorrhage (aICH), our review showed the lack of patient’s individual (i) timeline panels and (ii) serial brain CT/MRI slice through aICH evacuation neurointensive care until final tissue outcome. Methods Our retrospective cohort consists 54 consecutive patients from a defined population who acutely underwent clipping middle cerebral artery bifurcation saccular aneurysm (Mbif sIA) with at Kuopio University Hospital (KUH) 2010 to 2019. We constructed since emergency call The were indicated by numbers (1.–54.) in pseudonymized panels, tables, results, discussion. Results volumes on KUH admission (median 46 cm 3 ) plotted against time 8 hours) associated significantly rebleeds ( n =25) deaths =12). illustrated aICHs, intraventricular hemorrhages (aIVHs), residuals after evacuations, perihematomal edema (PHE), delayed injury (DCI), 42 survivors, clinical outcome (mRS) Conclusions Regarding present more information than words, figures, graphs. Re-bleeds larger worse outcomes. Swift logistics sIA occlusion is required, also duty hours weekends. Intraoperative CT needed illustrate degree evacuation. PHE may evoke uncontrollable intracranial pressure (ICP) spite acute volume reduction.

Language: Английский

---

The Haptoglobin Response after Aneurysmal Subarachnoid Haemorrhage

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(23), P. 16922 - 16922

Published: Nov. 29, 2023

Haptoglobin is the body's first line of defence against toxicity extracellular haemoglobin released following a subarachnoid haemorrhage (SAH). We investigated haptoglobin response after SAH in cerebrospinal fluid (CSF) and serum. Paired CSF serum samples from 19 controls 92 patients were assayed as follows: ultra-performance liquid chromatography for haptoglobin, immunoassay multiplexed cytokines, colorimetry albumin. There was marked deficiency: 99% unbound. The quotients both CSF/serum albumin (qAlb) (qHp) used to compute index (qHp/qAlb). had significantly lower compared controls, especially Haptoglobin-1 allele carriers. Serum levels increased correlated with cytokine levels. variables not associated long-term clinical outcomes post-SAH. conclude that: (1) intrathecal consumption occurs SAH, more so haptoglobin-1 carriers; (2) upregulated keeping liver acute phase central inflammation; (3) low that any variation too small this affect outcomes, emphasising potential therapeutic supplementation.

Language: Английский

---

Navigating Hemolysis, Hemoglobin Toxicity, and Its Renal Implications in Cardiac Surgery

Anesthesiology, Journal Year: 2024, Volume and Issue: 141(6), P. 1162 - 1174

Published: Aug. 19, 2024

Cardiopulmonary bypass–induced hemolysis is linked to acute kidney injury in cardiac surgery. Emerging therapies targeting cell-free hemoglobin, like haptoglobin, nitric oxide, and antioxidants, show promise reducing injury, highlighting the need for further research.

Language: Английский

---