A Rare Intersection of Septic Cavernous Sinus Thrombosis and Subarachnoid Hemorrhage: Insights from the Case of a 70-Year-Old Patient.

We describe a rare and complex case of septic cavernous sinus thrombosis (SCST) in a 70-year-old patient who initially presented with ocular symptoms that rapidly progressed to severe intracranial vascular complications, including subarachnoid hemorrhage (SAH). Despite the use of broad-spectrum antibiotics and anticoagulants, the patient's condition deteriorated. SCST, often caused by sinus infections, presents a significant diagnostic and therapeutic dilemma, with mortality rates exceeding 20%. This report underscores the diversity of clinical presentations, ranging from mild headaches to severe cranial nerve deficits, that complicate diagnosis and treatment. The inability to detect any aneurysms in our patient using magnetic resonance imaging (MRI) and computed tomography angiography (CTA) may indicate an alternative pathogenesis. This could involve venous hypertension and endothelial hyperpermeability. This case illustrates the need for personalized treatment approaches, as recommended by the European Federation of Neurological Societies, and the importance of a multidisciplinary perspective when managing such intricate neurological conditions. Our findings contribute to the understanding of SCST coexisting with SAH.

[Management of SAH]. / Prise en charge de la HSA.

Every year, the neurosurgical intensive care unit at Grenoble's university hospital (CHU) receives a large number of cerebrovascular patients. Data collected in the department during 2023 show that subarachnoid hemorrhage (SAH) is one of the most frequent causes of the pathologies treated. In this article, we focus on the appropriate course of action.

Effects of COVID-19 on the admissions of aneurysmal subarachnoid hemorrhage: the West Greece experience.

BACKGROUND: Acute subarachnoid hemorrhage (SAH) due to aneurysmal rupture is a devastating vascular disease accounting for 5% of strokes. COVID-19 pandemic resulted in a decrease in elective and emergency admissions in the majority of neurosurgical centers. The main hypothesis was that fear of COVID-19 may have prevented patients with critical medical or surgical emergencies from actively presenting in emergency departments and outpatient clinics. METHODS: We conducted a single-center, retrospective, observational study searching our institutional data regarding the incidence of spontaneous subarachnoid hemorrhage (SAH) and compare the admissions in two different periods: the pre COVID-19 with the COVID-19 period. RESULTS: The study cohort was comprised of a total of 99 patients. The mean (SD) weekly case rate of patients with SAH was 1.1 (1.1) during the pre-COVID-19 period, compared to 1.7 (1.4) during the COVID-19 period. Analysis revealed that the volume of admitted patients with SAH was 1.5-fold higher during the COVID period compared to the pre-COVID period and this was statistically significant (ExpB = 1.5, CI 95% 1-2.3, p = 0.044). Difference in mortality did not reach any statistical significance between the two periods (p = 0.097), as well as patients' length of stay (p = 0.193). CONCLUSIONS: The presented data cover a more extended time period than so far published reports; it is reasonable that our recent experience may well be demonstrating a general realistic trend of overall increase in aneurysmal rupture rates during lockdown. Hospitalization of patients with SAH cannot afford any reductions in facilities, equipment, or personnel if optimum outcomes are desirable.

Neuroprotective Strategies in Aneurysmal Subarachnoid Hemorrhage (aSAH).

Aneurysmal subarachnoid hemorrhage (aSAH) remains a disease with high mortality and morbidity. Since treating vasospasm has not inevitably led to an improvement in outcome, the actual emphasis is on finding neuroprotective therapies in the early phase following aSAH to prevent secondary brain injury in the later phase of disease. Within the early phase, neuroinflammation, thromboinflammation, disturbances in brain metabolism and early neuroprotective therapies directed against delayed cerebral ischemia (DCI) came into focus. Herein, the role of neuroinflammation, thromboinflammation and metabolism in aSAH is depicted. Potential neuroprotective strategies regarding neuroinflammation target microglia activation, metalloproteases, autophagy and the pathway via Toll-like receptor 4 (TLR4), high mobility group box 1 (HMGB1), NF-κB and finally the release of cytokines like TNFα or IL-1. Following the link to thromboinflammation, potential neuroprotective therapies try to target microthrombus formation, platelets and platelet receptors as well as clot clearance and immune cell infiltration. Potential neuroprotective strategies regarding metabolism try to re-balance the mismatch of energy need and supply following aSAH, for example, in restoring fuel to the TCA cycle or bypassing distinct energy pathways. Overall, this review addresses current neuroprotective strategies in aSAH, hopefully leading to future translational therapy options to prevent secondary brain injury.

Valproic Acid Reduces Vasospasm through Modulation of Akt Phosphorylation and Attenuates Neuronal Apoptosis in Subarachnoid Hemorrhage Rats.

Aneurysmal subarachnoid hemorrhage (SAH) is a devastating emergent event associated with high mortality and morbidity. Survivors usually experience functional neurological sequelae caused by vasospasm-related delayed ischemia. In this study, male Sprague-Dawley rats were randomly assigned to five groups: sham (non-SAH) group, SAH group, and three groups with SAH treated with different doses of valproic acid (VPA) (10, 20, 40 mg/kg, once-daily, for 7 days). The severity of vasospasm was determined by the ratio of cross-sectional areas to intima-media thickness of the basilar arteries (BA) on the seventh day after SAH. The BA showed decreased expression of phospho-Akt proteins. The dentate gyrus showed increased expression of cleaved caspase-3 and Bax proteins and decreased expression of Bcl-2, phospho-ERK 1/2, phospho-Akt and acetyl-histone H3 proteins. The incidence of SAH-induced vasospasm was significantly lower in the SAH group treated with VPA 40 mg/kg (p < 0.001). Moreover, all groups treated with VPA showed reversal of the above-mentioned protein expression in BA and the dentate gyrus. Treatment with VPA upregulated histone H3 acetylation and conferred anti-vasospastic and neuro-protective effects by enhancing Akt and/or ERK phosphorylation. This study demonstrated that VPA could alleviate delayed cerebral vasospasm induced neuro-apoptosis after SAH.

ß-Caryophyllene Liposomes Attenuate Neurovascular Unit Damage After Subarachnoid Hemorrhage in Rats.

This study was conducted to prepare ß-caryophyllene loaded liposomes (BCP-LP) and investigated their effects on neurovascular unit (NVU) damage after subarachnoid hemorrhage (SAH) in rats. A blood injection into the pre-chiasmatic cistern was used to achieve SAH. BCP-LP were prepared, characterized and administrated to rats with SAH. The prepared BCP-LP were spherical with a size distribution of approximately 189.3 nm and Zeta potential of - 13.9 mV. Neurological scoring, the balance beam test, cerebral blood flow monitoring, brain edema and biochemical analyses were applied to evaluate the effects of BCP-LP on rat NVU damage after SAH. The results demonstrated that BCP-LP treatment improved neurological function disorder, balance ability and cerebral blood perfusion in rats. Brain edema detection and blood-brain barrier permeability detection revealed that BCP-LP could reduce brain edema and promote repairment of blood-brain barrier after SAH. Using the western blot experiments, we demonstrated that BCP-LP attenuated the loss of tight junction proteins Occludin and Zonula occludens-1, inhibit the high expression of VEGFR-2 and GFAP, and promote the repair of laminin. These results demonstrate the protective effect BCP-LP exert in the NVU after SAH in rats, and supports the use of BCP-LP for future study and therapy of SAH.

HMGB1-Mediated Neuroinflammatory Responses in Brain Injuries: Potential Mechanisms and Therapeutic Opportunities.

Brain injuries are devastating conditions, representing a global cause of mortality and morbidity, with no effective treatment to date. Increased evidence supports the role of neuroinflammation in driving several forms of brain injuries. High mobility group box 1 (HMGB1) protein is a pro-inflammatory-like cytokine with an initiator role in neuroinflammation that has been implicated in Traumatic brain injury (TBI) as well as in early brain injury (EBI) after subarachnoid hemorrhage (SAH). Herein, we discuss the implication of HMGB1-induced neuroinflammatory responses in these brain injuries, mediated through binding to the receptor for advanced glycation end products (RAGE), toll-like receptor4 (TLR4) and other inflammatory mediators. Moreover, we provide evidence on the biomarker potential of HMGB1 and the significance of its nucleocytoplasmic translocation during brain injuries along with the promising neuroprotective effects observed upon HMGB1 inhibition/neutralization in TBI and EBI induced by SAH. Overall, this review addresses the current advances on neuroinflammation driven by HMGB1 in brain injuries indicating a future treatment opportunity that may overcome current therapeutic gaps.

Development of pseudo-subarachnoid hemorrhage secondary to hypoxic-ischemic injury due to bleeding pulmonary arterio-venous malformation.

BACKGROUND: The computed tomography (CT) finding of a pseudo-subarachnoid hemorrhage (SAH) may lead the treating physician into a diagnostic dilemma. We present a case of a pseudo-SAH in a patient with post-resuscitative encephalopathy, secondary to a newly diagnosed bleeding pulmonary arterio-venous malformation (AVM). CASE PRESENTATION: A 19-year-old female presented acutely with massive hemoptysis. Cardiopulmonary resuscitation (CPR) followed, and the patient was subsequently intubated for airway protection with intensive care unit (ICU) admission. Urgent CT angiography of the thorax showed a bleeding pulmonary AVM, with evidence of hemothorax. Non-contrasted cranial CT initially revealed cerebral edema. Day 3 post admission, repeat cranial CT showed worsening cerebral edema, with evidence of pseudo-SAH. Patient passed away the next day. CONCLUSIONS: Pseudo-SAH, if present, carries a poor prognosis. It should be recognized as a potential CT finding in patients with severe cerebral edema, due to various causes. The diagnosis is vital, to avoid wrongful treatment institution, as well as determination of cause of death.

Rush progression and fatal result of septic shock related to central line catheter infection in cirrhosis patient with brain stroke.

BACKGROUND: Catheter-related blood stream infection (CRBSI) is one of the most common intractable healthcare-associated infections because catheters can be easily contaminated by resistant bacteria, and is associated with a high mortality. Central lines are currently used for administering medication to patients with severe stroke, and may thus cause CRBSI. CASE PRESENTATION: A 71-year-old woman with cirrhosis presented with subarachnoid hemorrhage (SAH) that was treated by clipping surgery. On postoperative day (POD) 38, sudden high fever (40.3 °C) was detected; the patient died a few hours later. Blood and central line cultures were positive for Klebsiella pneumoniae that may have caused CRBSI and endotoxin shock. In this case, the duration from fever detection to death was notably short. Additionally, inflammatory markers such as white blood cells (WBC) or C-reactive protein (CRP) were almost within normal ranges, even a few hours after fever was detected and before death. Cirrhosis was considered to be the cause of these phenomena. CONCLUSION: The timely diagnosis and complete treatment of patients with liver cirrhosis who develop CRBSI are highly challenging. We suggest that clinicians should rigorously apply preventive measures and strengthen CRBSI monitoring, especially in cirrhosis-associated cases.

Side Effects of Long-Term Continuous Intra-arterial Nimodipine Infusion in Patients with Severe Refractory Cerebral Vasospasm after Subarachnoid Hemorrhage.

BACKGROUND: Long-term continuous intra-arterial nimodipine infusion (CIAN) is a rescue therapy option in cases of severe refractory cerebral vasospasm (CV) following acute non-traumatic subarachnoid hemorrhage (SAH). However, CIAN therapy can be associated with relevant side effects. Available studies focus on intracerebral complications, whereas extracerebral side effects are rarely examined. Aim of the present study was to generate descriptive data on the clinical course during CIAN therapy and expectable extracerebral side effects. METHODS: All patients treated with CIAN therapy for at least 5 days between May 2011 and December 2015 were included. We retrospectively extracted data from the patient data management system regarding the period between 2 days before the beginning and 5 days after the termination of CIAN therapy to analyze the course of ventilation parameters and pulmonary gas exchange, hemodynamic support, renal and liver function, integrity of the gastrointestinal tract, and the occurrence of infectious complications. In addition, we recorded the mean daily values of intracranial pressure (ICP) and intracerebral problems associated with CIAN therapy. RESULTS: Data from 28 patients meeting inclusion criteria were analyzed. The mean duration of long-term CIAN therapy was 10.5 ± 4.5 days. Seventeen patients (60.7%) reached a good outcome level (Glasgow Outcome Scale [GOS] 4-5) 6 months after SAH. An impairment of the pulmonary gas exchange occurred only at the very beginning of CIAN therapy. The required vasopressor support with norepinephrine was significantly higher on all days during and the first day after CIAN therapy compared to the situation before starting CIAN therapy. Two patients required short-time resuscitation due to cardiac arrest during CIAN therapy. Acute kidney injury was observed in four patients, and one of them required renal replacement therapy with sustained low-efficiency daily dialysis. During CIAN therapy, 23 patients (82.1%) needed the escalation of a previous antiinfective therapy or the onset of antibiotics which was in line with a significant increase of C-reactive protein and white blood cell count. Obstipation was observed in 22 patients (78.6%). Ten patients (35.7%) even showed insufficient defecation on at least seven consecutive days. Compared to the situation before, ICP was significantly higher during the whole period of CIAN therapy. CONCLUSIONS: Long-term CIAN therapy is associated with diverse side effects. The leading problems are an impairment of the hemodynamic situation and cardiac problems, an increase in infectious complications, a worsening of the motility of the gastrointestinal tract, and rising ICP values. Teams on neurointensive care units must be aware of these side effects to avoid that the beneficial effects of CIAN therapy on CV reported elsewhere are foiled by the problems this technique can be associated with.

Spontaneous Elevation of Blood Pressure After SAH: An Epiphenomenon of Disease Severity and Demand, But Not a Surrogate for Outcome?

BACKGROUND: Spontaneous blood pressure increase is frequently observed after aneurysmal subarachnoid hemorrhage (aSAH). These episodes of spontaneous blood pressure alterations are usually tolerated under the assumption of an endogenous response to maintain cerebral perfusion. The relevance of blood pressure variability and its relationship to disease severity and outcome, however, remain obscure. METHODS: A total of 115 consecutive patients with aSAH were included for this retrospective analysis of a continuously collected data pool. Demographics, initial clinical severity of aSAH (HH°, mFS), treatment modality, clinical course, and outcome (development of DCI, cerebral infarction, and GOS after 3 months) were recorded. Hemodynamic information-recorded automatically with a frequency of 1/15 min-was analyzed for spontaneous blood pressure increase (SBI) and endogenous persistent hypertension (EPH) after exclusion of iatrogenic factors and relevant co-medication. Subgroup analysis included stratification for day 0-3, 4-14, and 14-21. RESULTS: SBI and EPH incidence varied from 17 to 84% depending on detection threshold (15-35 mmHg) and time period under scrutiny. Incidence of blood pressure increase correlated with disease severity upon admission (p < 0.05), but the anticipated association with outcome was not observed. SBI and EPH were more likely to occur between day 4 and 14 (p < 0.001), but only early occurrence (day 0-3) was associated with higher incidence of DCI (p < 0.05). Persistent blood pressure elevation between day 4 and 21 was associated with fewer DCI. However, no influence of spontaneous upregulation on clinical outcome after three months was observed. CONCLUSIONS: Spontaneous hemodynamic upregulation is a frequent phenomenon after aSAH. Our data support the hypothesis that spontaneous blood pressure alterations reflect an endogenous, demand-driven response correlating with disease severity. Early alterations may indicate an aggravated clinical course, while later upregulation in particular-if permitted-does not translate into a higher risk of unfavorable outcome.

Effect of HHH-Therapy on Regional CBF after Severe Subarachnoid Hemorrhage Studied by Bedside Xenon-Enhanced CT.

BACKGROUND: Management of delayed cerebral ischemia (DCI) following subarachnoid hemorrhage (SAH) is difficult and still carries controversies. In this study, the effect of therapeutic hypervolemia, hemodilution, and hypertension (HHH-therapy) on cerebral blood flow (CBF) was assessed by xenon-enhanced computerized tomography (XeCT) hypothesizing an increase in CBF in poorly perfused regions. METHODS: Bedside XeCT measurements of regional CBF in mechanically ventilated SAH patients were routinely scheduled for day 0-3, 4-7, and 8-12. At clinical suspicion of DCI, patients received 5-day HHH-therapy. For inclusion, XeCT was required at 0-48 h before start of HHH (baseline) and during therapy. Data from corresponding time-windows were also collected for non-DCI patients. RESULTS: Twenty patients who later developed DCI were included, and twenty-eight patients without DCI were identified for comparison. During HHH, there was a slight nonsignificant increase in systolic blood pressure (SBP) and a significant reduction in hematocrit. Median global cortical CBF for the DCI group increased from 29.5 (IQR 24.6-33.9) to 38.4 (IQR 27.0-41.2) ml/100 g/min (P = 0.001). There was a concomitant increase in regional CBF of the worst vascular territories, and the proportion of area with blood flow below 20 ml/100 g/min was significantly reduced. Non-DCI patients showed higher CBF at baseline, and no significant change over time. CONCLUSIONS: HHH-therapy appeared to increase global and regional CBF in DCI patients. The increase in SBP was small, while the decrease in hematocrit was more pronounced, which may suggest that intravascular volume status and rheological effects are of importance. XeCT may be potentially helpful in managing poor-grade SAH patients.

[Prevalence of acute symptomatic seizure after intracerebral hemorrhage].

OBJECTIVE: Introduсtion: Acute symptomatic seizure (ASS) is a most frequently complication after a stroke. Seizures could be associated with the worse outcome. Nowadays the prophylactic antiepileptic treatment after the stroke is not advisable. However this question have to be discussed in a particular groups of patients. The aim: To study the prevalence of ASS in the particular groups of patients after intracerebral hemorrhage as well as to determine the predictors of the sizure occurrence in these groups of patients. PATIENTS AND METHODS: Materials and methods: The retrospective analysis of the clinical features of intracerebral hemorrhage for 305 patients was performed. Among them there were 127 patients with aneurysmal subarachnoid hemorrhage as well as 178 patients were with nonaneurysmal intracerebral hemorrhage. RESULTS: Results: In 12 patients from 127 with subarachnoid hemorrhage were occurred onset seizures. 4 patients from 12 with subarachnoid hemorrhage died (28.5% of all deaths in the group of patients with subarachnoid hemorrhage (SAH)). In the group of patients with seizures 10 of them had aneurysm in anterior part of Willi's Circle. In 11 patients from 178 with nonaneurysmal intracerebral hemorrhage occurred onset seizures. Only one patient from 72 with medial localization of intracerebral hemorrhage had seizures. CONCLUSION: Conclusions: Prevalence of ASS after intracerebral hemorrhage reaches 7.5%, in the group of patients with SAH - 9.5%, in the group of patients with intracerebral nonaneurysmal hemorrhage - 6.25%. Initial seizures at the onset of subarachnoid hemorrhage is an unfavorable prognostic criteria and is associated with higher mortality. Localization of aneurysm in anterior part of Willi's Circle and lateral localisation of intracerebral hemorrhage are associated with a higher risk of the ASS development.

Ethyl Pyruvate Attenuates Early Brain Injury Following Subarachnoid Hemorrhage in the Endovascular Perforation Rabbit Model Possibly Via Anti-inflammation and Inhibition of JNK Signaling Pathway.

Early brain injury (EBI) following subarachnoid hemorrhage (SAH) is the main cause to poor outcomes of SAH patients, and early inflammation plays an important role in the acute pathophysiological events. It has been demonstrated that ethyl pyruvate (EP) has anti-inflammatory and neuroprotective effects in various critical diseases, however, the role of EP on EBI following SAH remains to be elucidated. Our study aimed to evaluate the effects of EP on EBI following SAH in the endovascular perforation rabbit model. All rabbits were randomly divided into three groups: sham, SAH + Vehicle (equal volume) and SAH + EP (30 mg/kg/day). MRI was performed to estimate the reliability of the EBI at 24 and 72 h after SAH. Neurological scores were recorded to evaluate the neurological deficit, ELISA kit was used to measure the level of tumor necrosis factor-α (TNF-α), and western blot was used to detect the expression of TNF-α, tJNK, pJNK, bax and bcl-2 at 24 and 72 h after SAH. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) and Fluoro-jade B (FJB) staining were used to detect neuronal apoptosis and neurodegeneration respectively, meanwhile hematoxylin and eosin (H&E) staining was used to assess the degree of vasospasm. Our results demonstrated that EP alleviated brain tissue injury (characterized by diffusion weighted imaging and T2 sequence in MRI scan), and significantly improved neurological scores at 72 h after SAH. EP decreased the level of TNF-α and downregulated pJNK/tJNK and bax/bcl-2 in cerebral cortex and hippocampus effectively both at 24 and 72 h after SAH. Furthermore, EP reduced TUNEL and FJB positive cells significantly. In conclusion, the present study supported that EP afforded neuroprotective effects possibly via reducing TNF-α expression and inhibition of the JNK signaling pathway. Therefore, EP may be a potent therapeutic agent to attenuate EBI following SAH.

[Plasma Free mtDNA and Expression of TLR-9/MAPK in Brain Tissues of Rats with Subarachnoid Hemorrhage].

OBJECTIVES: To determine the plasma level of mitochondrial DNA (mtDNA) and the expression of Toll like receptor-9/mitogen-activated protein kinase (TLR-9/MAPK) in the brain tissues of rats with subarachnoid hemorrhage (SAH). METHODS: Sprague-Dawley rats were used to establish SAH models with a modified method of endovascular perforation. Twenty four hours after the establishment of the models, the plasma level of mtDNA in the rats was detected by real-time PCR; the expressions of TLR-9 and P38 MAPK in the brain tissues were detected by reverse transcription PCR (RT-PCR) and immunohistochemical staining. Differences between the SAH (n =20) and sham-surgical (n =20) groups were compared. RESULTS: Rats in the SAH group had higher levels of plasma mtNDA and expressions of TLR-9 and P38 MAPK in brain tissues than those in the sham-surgical group (P <0.05). CONCLUSION: Plasma free mtDNA and expressions of TLR-9/MAPK increase simultaneously in rats with SAH. mtDNA may induce system and local inflammation reactions in brain.

[Pathological changes in the microstructure of the sensomotor cortex of white rats with experimental subarachnoid hemorrhage and after experimental influences].

INTRODUCTION: Many works are dedicated to research in the experiment of the cerebrovascular diseases and correction of pathological changes. Among these studies we have not found devoted czuciowo-ruchowej changes cortex of rats subarachnoid hemorrhage. MATERIAL AND METHODS: The study was conducted on 18 white rats weighing 220-310 g. The model of subarachnoid hemorrhage (SAH) was created on the base of methodology described by Dudhani RV et al. (2013). SAH develops immediately after injection of autologous arterial blood into the subarachnoid space. Five animals underwent everyday intraperitoneal injection of NO Donator (L-arginine aspartate) for 8 days from the beginning of the experiment. Sampling of the biological material carried on the ninth day after euthanasia of the test animals under anesthesia with diethyl ether. RESULTS: Swollen, rounded shape neurons were observed while watching the microscope slides of rat brain samples after autologous blood injection. Otherwise, others cells in the same sample looked atrophous, of reduced size, shrunken. There was observed increase in surface area to 623.1 ± 36.0 µm² and volume of neurons to 949.8±78.0 mkm³, significant compared to healthy animals. The severity of pathologic changes was lower in group of therapy by NO donator, namely, the bodies of neurons of the similar size, their shape is almost triangular, most neurons also as macroglial cells have close to normal structure and pericellular zone. CONCLUSIONS: SAH evokes a number of pathological changes in the rats' brain sensomotor cerebral cortex. Modeling of the SAH leads to significant (p<0,01) morphometric changes in the pyramidal neurons, namely, to increase of the surface of nerve cells in an average up 1.33 times and 1.5 times - of the volume. Therapy by NO donator of animals with model of SAH reduces the severity of cells' lesion, the majority of neurons and macroglial cells have the shape and pericellular spaces close to the normal.

Blood Pressure Guideline Adherence in Patients with Ischemic and Hemorrhagic Stroke in the Neurointensive Care Unit Setting.

BACKGROUND AND PURPOSE: Patients with acute brain injuries require strict physiologic control to minimize morbidity and mortality. This study aimed to assess in-hospital compliance to strict physiologic parameters (BP, HR, ICP, SpO2) in these populations. METHODS: Patients with severe cerebrovascular events were admitted to the neurointensive care unit (NSICU) and were continuously monitored using the BedMasterEX (Excel Medical Electronics Inc, FL) system, which recorded hemodynamic data via an arterial catheter continuously in 5-s intervals. Furthermore, we investigated the impact of healthcare provider shift changes (6-8 a.m./p.m) and of day (6 a.m.-6 p.m.) versus night (6 p.m-6 a.m) shifts in hemodynamic control. RESULTS: Fifty patients admitted to the NSICU, 50 % male, mean age 59.7 ± 13.9 years with subarachnoid hemorrhage (23), ischemic stroke (8), subdural hematoma (4), intracerebral hemorrhage (3), intraventricular hemorrhage (2), and miscellaneous injuries (10) were enrolled. Data represented 2,337 total hours of continuous monitoring. Systolic BPs (SBP) were on average outside of recommended ranges 32.26 ± 30.46 % of the monitoring period. We subdivided adherence to ideal SBP range: optimal (≥99 % of time spent in NSICU within range) was achieved in 12 %, adequate (90 %) in 16 %, suboptimal (80 %) in 20 %, inadequate I (70 %) in 12 %, and inadequate II (<70 %) in 40 % of patients. Comparison of shift change %time and day versus night %time out of parameter yielded no statistically significant differences across SAH patients. CONCLUSION: Hemodynamic management of patients with cerebrovascular injuries, based on targeted thresholds in the NSICU, yielded optimal control of SBP in only 28 % of our patients (within parameters ≥90 % of time).

Inhibiting RIPK1-driven neuroinflammation and neuronal apoptosis mitigates brain injury following experimental subarachnoid hemorrhage.

RIPK1, a receptor-interacting serine/threonine protein kinase, plays a crucial role in maintaining cellular and tissue homeostasis by integrating inflammatory responses and cell death signaling pathways including apoptosis and necroptosis, which have been implicated in diverse physiological and pathological processes. Suppression of RIPK1 activation is a promising strategy for restraining the pathological progression of many human diseases. Neuroinflammation and neuronal apoptosis are two pivotal factors in the pathogenesis of brain injury following subarachnoid hemorrhage (SAH). In this study, we established in vivo and in vitro models of SAH to investigate the activation of RIPK1 kinase in both microglia and neurons. We observed the correlation between RIPK1 kinase activity and microglia-mediated inflammation as well as neuronal apoptosis. We then investigated whether inhibition of RIPK1 could alleviate neuroinflammation and neuronal apoptosis following SAH, thereby reducing brain edema and ameliorating neurobehavioral deficits. Additionally, the underlying mechanisms were also explored. Our research findings revealed the activation of RIPK1 kinase in both microglia and neurons following SAH, as marked by the phosphorylation of RIPK1 at serine 166. The upregulation of p-RIPK1(S166) resulted in a significant augmentation of inflammatory cytokines and chemokines, including TNF-α, IL-6, IL-1α, CCL2, and CCL5, as well as neuronal apoptosis. The activation of RIPK1 in microglia and neurons following SAH could be effectively suppressed by administration of Nec-1 s, a specific inhibitor of RIPK1. Consequently, inhibition of RIPK1 resulted in a downregulation of inflammatory cytokines and chemokines and attenuation of neuronal apoptosis after SAH in vitro. Furthermore, the administration of Nec-1 s effectively mitigated neuroinflammation, neuronal apoptosis, brain edema, and neurobehavioral deficits in mice following SAH. Our findings suggest that inhibiting RIPK1 kinase represents a promising therapeutic strategy for mitigating brain injury after SAH by attenuating RIPK1-driven neuroinflammation and neuronal apoptosis.

Initial real-world experience of clazosentan for subarachnoid hemorrhage in Japan.

BACKGROUND: Cerebral vasospasm (CVS) is one of the most critical factors associated with clinical outcomes of patients with subarachnoid hemorrhage (SAH). Clazosentan has been investigated worldwide as a prophylactic agent to prevent CVS. We evaluated a new CVS management protocol which included clazosentan. METHODS: Consecutive 138 patients with SAH, hospitalized in our institution between January 2017 and December 2022, were included in this study. Baseline characteristics, clinical findings, and operative records were analyzed retrospectively. From May 2022, 10 mg/h clazosentan was co-administered with fasudil to all patients according to the indication in the Japanese label. Patients admitted before this date received the conventional combined protocol using the fasudil hydrochloride, nicardipine, and ozagrel. RESULTS: Eighteen (13.0%) patients received the new protocol during the CVS period (defined as day 1 up to day 14 after SAH onset). There were 54 (39.1%) elderly patients aged 75 years or older. Seventy-two (52.2%) patients underwent neurosurgical clipping, whereas 55 (39.9%) patients received endovascular coiling. Among the patients with new protocol, only one patient (5.6%) had symptomatic CVS, compared with 18 patients (15.0%) in those with conventional protocol. More patients who received the new protocol had fluid retention compared with control group (38.9% [7/18] vs. 8.3% [10/120]). Other results did not differ between the two groups. CONCLUSIONS: Clinical outcomes of the new protocol were comparable to those of conventional protocol. Clazosentan may simplify anti-vasospasm treatment. Fluid retention was a specific side-effect of clazosentan, which requires attention especially in the first half of the CVS period.

Nrf-2 modulates excitability of hippocampal neurons by regulating ferroptosis and neuroinflammation after subarachnoid hemorrhage in rats.

Excitability of hippocampal neurons in subarachnoid hemorrhage (SAH) rats has not been well studied. The rat SAH model was applied in this study to explore the role of nuclear factor E2-related factor (Nrf-2) in the early brain injury of SAH. The neural excitability of CA1 pyramidal cells (PCs) in SAH rats was evaluated by using electrophysiology experiments. Ferroptosis and neuroinflammation were measured by ELISA, transmission electron microscopy and western blotting. Our results indicated that SAH induced neurological deficits, brain edema, ferroptosis, neuroinflammation and neural excitability in rats. Ferrostatin-1 treatment significantly decreased the expression and distribution of IL-1ß, IL-6, IL-10, TGF-ß and TNF-α. Inhibiting ferroptosis by ferrostatin-1 can attenuate neural excitability, neurological deficits, brain edema and neuroinflammation in SAH rats. Inhibiting the expression of Nrf-2 significantly increased the neural excitability and the levels of IL-1ß, IL-6, IL-10, TGF-ß and TNF-α in Fer-1-treated SAH rats. Taken together, inhibiting the Nrf-2 induces early brain injury, brain edema and the inflammatory response with increasing of neural excitability in Fer-1-treated SAH rats. These results have indicated that inhibiting ferroptosis, neuroinflammation and neural excitability attenuates early brain injury after SAH by regulating the Nrf-2.