Comparison of scales for the evaluation of aneurysmal subarachnoid haemorrhage: a retrospective cohort study.

BACKGROUND/OBJECTIVES: Aneurysmal subarachnoid haemorrhage (aSAH) is a life-threatening event with major complications. Delayed cerebral infarct (DCI) occurs most frequently 7 days after aSAH and can last for a prolonged period. To determine the most predictive radiological scales in grading subarachnoid or ventricular haemorrhage or both for functional outcome at 3 months in a large aSAH population, we conducted a single-centre retrospective study. METHODS: A 3-year single-centre retrospective cohort study of 230 patients hospitalised for aSAH was analysed. Initial computed tomography (CT) scans in patients hospitalised for aSAH were blindly assessed using eight grading systems: the Fisher grade, modified Fisher grade, Barrow Neurological Institute scale, Hijdra scale, Intraventricular Haemorrhage (IVH) score, Graeb score and LeRoux score. RESULTS: Of 200 patients with aSAH who survived to day 7 and were included for DCI analysis, 39% of cases were complicated with DCI. The Hijdra scale was the best predictor for DCI, with a receiver operating characteristic area under the curve (ROCAUC) of 0.80 (95% confidence interval (CI), 0.74-0.85). The IVH score was the most effective grading system for predicting acute hydrocephalus, with a ROCAUC of 0.85 (95% CI, 0.79-0.89). In multivariate analysis, the Hijdra scale was the best predictor of the occurrence of DCI (hazard ratio, 1.18; 95% CI, 1.10-1.25). CONCLUSIONS: Although these results have yet to be prospectively confirmed, our findings suggest that the Hijdra scale may be a good predictor of DCI and could be useful in daily clinical practice. CLINICAL RELEVANCE STATEMENT: Better assessment of subarachnoid haemorrhage patients would allow for better prognostication and management of expectations, as well as referral for appropriate services and helping to appropriate use limited critical care resources. KEY POINTS: Aneurysmal subarachnoid haemorrhage is a life-threatening event that causes severe disability and leads to major complications such as delayed cerebral infarction. Accurate assessment of the amount of blood in the subarachnoid spaces on computed tomography with the Hijdra scale can better predict the risk of delayed cerebral infarct. The Hijdra scale could be a good triage tool for subarachnoid haemorrhage patients.

Lung Function and Brain MRI Outcomes in the Atherosclerosis Risk in Communities Neurocognitive Study.

Background: Brain imaging studies may provide etiologic insight into observed links between lung function and dementia and stroke. Objective: We evaluated associations of lung function measures with brain MRI markers of vascular and neurodegenerative disease in the ARIC Neurocognitive Study, as few studies have examined the associations. Methods: Lung function was measured at participants' midlife in 1990-1992 (mean age = 56±5 years) and later-life in 2011-2013 (mean age = 76±5 years), and brain MRI was performed in 2011-2013. Linear regression models were used to examine the associations of lung function with brain and white matter hyperintensity (WMH) volumes, and logistic regression models were used for cerebral infarcts and microbleeds, adjusting for potential confounders. Results: In cross-sectional analysis (i.e., examining later-life lung function and MRI markers, n = 1,223), higher forced-expiratory volume in one second (FEV1) and forced vital capacity (FVC) were associated with larger brain and lower WMH volumes [e.g., 8.62 (95% CI:2.54-14.71) cm3 greater total brain volume per one-liter higher FEV1]. No association was seen with microbleeds in the overall sample, but higher FVC was associated with lower odds of microbleeds in never-smokers and higher odds in ever-smokers. In the cross-temporal analysis (i.e., associations with midlife lung function, n = 1,787), higher FVC levels were significantly associated with lower later-life brain volumes. Conclusions: Our results support modest associations of better lung function with less neurodegenerative and cerebrovascular pathology, although findings for microbleeds were unexpected in ever-smokers.

Brucella infection presenting as infective endocarditis complicated by embolic stroke.

Brucellosis (undulant fever) is a zoonotic infection caused by Brucella species. It typically presents with fever, malaise, night sweats, and arthralgia. One of its rare complications is infective endocarditis, which occurs in approximately 1.3% of patients and can be further complicated by embolic stroke. This report describes a rare occurrence of Brucella endocarditis presenting as an embolic stroke. A 34-year-old male presented with sudden left-sided weakness and fever. He reported headaches, fever, and generalized weakness in the preceding week. The patient worked on a farm and hence had animal contact. A neurological exam showed left-sided facial weakness, and power of 0/5 and 1/5 in the left upper and lower extremities, respectively. CT scan of the head revealed a right middle cerebral artery (MCA) territory infarct with penumbra and a right MCA occlusion. He underwent a cerebral artery thrombectomy with successful recanalization. However, he continued to have fever and high inflammatory markers. Echocardiography showed aortic valve vegetation and blood cultures grew Brucella melitensis. A multidisciplinary meeting was held to determine the optimal management, which included a course of rifampicin and doxycycline.

Cerebrofacial arteriovenous metameric syndrome type I + II + III: An unusual case.

Cerebrofacial arteriovenous Metameric syndrome (CAMS) typically manifests as types I, II, or III, occasionally presenting as dual types. Our unique case underscores the coexistence of all three CAMS types in one patient. Furthermore, the concurrent acute cerebellar infarct underscores the need to consider CAMS in the differential diagnosis of adolescents experiencing neurological events.

Frequency and predictors of decompressive craniectomy in ischemic stroke patients treated by mechanical thrombectomy in the ETIS registry.

BACKGROUND AND AIMS: Mechanical thrombectomy (MT) for patients with acute ischemic stroke (AIS) is usually performed in a comprehensive stroke center with on-site neurosurgical expertise. The question of whether MT can be performed in a primary stroke center without a neurosurgical facility is debated. In this context, there is a need to determine the frequency, delay and predictors of neurosurgical procedures in patients treated by MT. This study aims to determine these factors. METHODS: In total, 432 patients under 60years old, diagnosed with an acute ischemic stroke with a large vessel occlusion and treated by MT between January 2018 and December 2019 in six French stroke centers, were selected from the French clinical registry ETIS. Univariate and multivariate logistic regression models were used to identify predictive factors for decompressive craniectomy. RESULTS: Among the 432 included patients, 43 (9.9%) patients with an anterior circulation infarct underwent decompressive craniectomy. Higher admission NIHSS (OR: 1.08 [95% CI: 1.02-1.16]), lower ASPECT (OR per 1 point of decrease 1.53 [1.31-1.79] P<0.001) and preadmission antiplatelet use (OR: 3.03 [1.31-7.01]) were independent risk factors for decompressive craniectomy. The risk of decompressive craniectomy increases to more than 30% with an ASPECT score<4, an NIHSS>16, and current antiplatelet use. CONCLUSION: In this multicenter registry, 9% of acute ischemic stroke patients (<60years old) treated with MT, required decompressive craniectomy. Higher NIHSS score, lower ASPECT score, and preadmission antiplatelet use increase the risk of subsequent requirement for decompressive craniectomy.

Miliary brain tuberculomas and tuberculous meningitis presenting with stroke.

Even though it is an uncommon presentation of tuberculosis, tuberculous meningitis is one of the most deadly manifestations. We report a case of a 6-year-old female who presented to the emergency room for left hemiparesis. Cerebral CT and MRI showed a right ischemic stroke with severe leptomeningitis in the medial cranial fossa. Numerous miliary tuberculomas were demonstrated, as well as a moderate hydrocephalus. Lumbar puncture revealed meningitis, and the mycobacterium tuberculosis polymerase chain reaction from CSF was positive. Pulmonary micronodules on chest CT were suggestive of tuberculosis. The clinical and radiological features, as well as the management approaches of this unusual disease complex, are addressed.

Prediction of motor outcome based on brain perfusion single photon emission computed tomography in corona radiata infarct.

BACKGROUND: There is limited information on brain perfusion single-photon emission computed tomography (SPECT) findings related to motor outcomes in patients with stroke. We aimed to investigate whether brain SPECT can be used to determine motor outcomes after corona radiata infarction. METHODS: Eighty-nine patients were recruited in this study. Brain SPECT and diffusion tensor tractography (DTT) were conducted to evaluate the state of the corticospinal tract (CST) within 7-30 days of corona radiata infarct. Motor outcome was measured 6 months after infarct onset and was evaluated using the modified Brunnstrom classification (MBC) and functional ambulation category (FAC) for motor function of the upper and lower extremities, respectively. The presence of hypoperfusion on brain SPECT was evaluated in the frontal lobe, temporal lobe, parietal lobe, basal ganglia, thalamus, and cerebellum on both the ipsilesional and contralesional sides. Statistical analysis was performed using multivariate logistic regression, comparing patients in which CST was spared versus interrupted. RESULTS: Hypoperfusion in the contralesional cerebellum was indicative of poor recovery in both the upper and lower extremities after corona radiata infarction when the CST was interrupted. Additionally, when the CST was preserved, hypoperfusion in the ipsilesional thalamus was indicative of poor recovery of the lower extremities. CONCLUSION: Brain SPECT evaluation was shown to be a useful tool for predicting motor outcomes in patients with corona radiata infarcts.

Possible involvement of inflammasomes on the post-stroke cognitive impairment in a mouse model of embolic cerebral infarct.

Post-stroke cognitive impairment (PSCI) of the complications after stroke has been shown to be involved in brain proinflammatory cytokines such as interleukin (IL)-1ß (IL-lß) and IL-18. In the present study, we examined using acetic acid-induced embolic cerebral infarct (ECI) mice whether post-stroke inflammasome activation is involved in the development of PSCI. In behavioral tests, long-term learning and memory assessed using the passive avoidance test were impaired after ECI. On the other hand, the impairment of short-term learning and memory assessed using the Y-maze test was not observed. Furthermore, the phosphorylated α-amino-3hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor subunit glutamate receptor 1 (GluR1) at Ser 831 and Ser 845 protein was found to be significantly decreased in the dorsal hippocampus of ECI mice. In addition, the expression levels of ionized calcium-binding adapter protein 1 (Iba1), glial fibrillary acidic protein (GFAP), apoptosis-associated speck-like protein containing a caspase recruitment domain / target of methylation-induced silencing 1 (ASC/TMS1), Caspase-1, IL-1ß, IL-18 and tumor necrosis factor-α (TNF-α) were significantly increased in the dorsal hippocampus of ECI mice. These results indicate that development of PSCI after embolic cerebral infarction is due to a decrease in AMPA receptor subunit GluR1 at Ser831 and Ser845 through the inflammasome activation pathway in the dorsal hippocampus.

The GPER1 agonist G1 reduces brain injury and improves the qEEG and behavioral outcome of experimental ischemic stroke.

Stroke is one of the principal cerebrovascular diseases in human populations and contributes to a majority of the functional impairments in the elderly. Recent discoveries have led to the inclusion of electroencephalography (EEG) in the complementary prognostic evaluation of patients. The present study describes the EEG, behavioral, and histological changes that occur following cerebral ischemia associated with treatment by G1, a potent and selective G protein-coupled estrogen receptor 1 (GPER1) agonist in a rat model. Treatment with G1 attenuated the neurological deficits induced by ischemic stroke from the second day onward, and reduced areas of infarction. Treatment with G1 also improved the total brainwave power, as well as the theta and alpha wave activity, specifically, and restored the delta band power to levels similar to those observed in the controls. Treatment with G1 also attenuated the peaks of harmful activity observed in the EEG indices. These improvements in brainwave activity indicate that GPER1 plays a fundamental role in the mediation of cerebral injury and in the behavioral outcome of ischemic brain injuries, which points to treatment with G1 as a potential pharmacological strategy for the therapy of stroke.

Wallerian degeneration of the ipsilateral middle cerebellar peduncle after lower pontine paramedian infarct diagnosed by magnetic resonance imaging.

We reported a case of Wallerian degeneration of the unilateral middle cerebellar peduncle (MCP) that developed after ipsilateral paramedian lower pontine infarction. The patient was a 70-year-old woman with right hemiparesis and dysarthria. Using a 3-Tesla scanner, cranial magnetic resonance imaging was performed, and an infarct was found at the left paramedian lower pons. Seven months later, an abnormal signal was found at the central portion of the left MCP, indicative of Wallerian degeneration of the pontocerebellar tract (PCT). There was no abnormality at the contralateral MCP. Usually, Wallerian degeneration of the bilateral MCPs may develop after unilateral paramedian pontine infarction, because bilateral PCTs cross each other at the midline of the basis pontis. In the present case, however, Wallerian degeneration was found at only the ipsilateral MCP. The contralateral PCT was not affected because the PCT runs in the craniocaudal direction, and our patient had a lower pontine infarct. The location of the pontine infarct (affected PCT) and the Wallerian degeneration of the side of the MCP were well correlated.

Toward Automated Detection of Silent Cerebral Infarcts in Children and Young Adults With Sickle Cell Anemia.

BACKGROUND: Silent cerebral infarcts (SCI) in sickle cell anemia (SCA) are associated with future strokes and cognitive impairment, warranting early diagnosis and treatment. Detection of SCI, however, is limited by their small size, especially when neuroradiologists are unavailable. We hypothesized that deep learning may permit automated SCI detection in children and young adults with SCA as a tool to identify the presence and extent of SCI in clinical and research settings. METHODS: We utilized UNet-a deep learning model-for fully automated SCI segmentation. We trained and optimized UNet using brain magnetic resonance imaging from the SIT trial (Silent Infarct Transfusion). Neuroradiologists provided the ground truth for SCI diagnosis, while a vascular neurologist manually delineated SCI on fluid-attenuated inversion recovery and provided the ground truth for SCI segmentation. UNet was optimized for the highest spatial overlap between automatic and manual delineation (dice similarity coefficient). The optimized UNet was externally validated using an independent single-center prospective cohort of SCA participants. Model performance was evaluated through sensitivity and accuracy (%correct cases) for SCI diagnosis, dice similarity coefficient, intraclass correlation coefficient (metric of volumetric agreement), and Spearman correlation. RESULTS: The SIT trial (n=926; 31% with SCI; median age, 8.9 years) and external validation (n=80; 50% with SCI; age, 11.5 years) cohorts had small median lesion volumes of 0.40 and 0.25 mL, respectively. Compared with the neuroradiology diagnosis, UNet predicted SCI presence with 100% sensitivity and 74% accuracy. In magnetic resonance imaging with SCI, UNet reached a moderate spatial agreement (dice similarity coefficient, 0.48) and high volumetric agreement (intraclass correlation coefficient, 0.76; ρ=0.72; P<0.001) between automatic and manual segmentations. CONCLUSIONS: UNet, trained using a large pediatric SCA magnetic resonance imaging data set, sensitively detected small SCI in children and young adults with SCA. While additional training is needed, UNet may be integrated into the clinical workflow as a screening tool, aiding in SCI diagnosis.

Transcranial Doppler Ultrasonography detection on cerebrovascular flow for evaluating neonatal hypoxic-ischemic encephalopathy modeling.

Objective: This study aimed to investigate the feasibility of Transcranial Doppler Ultrasonography (TCD) in evaluating neonatal hypoxic-ischemic encephalopathy (NHIE) modeling through monitoring the alteration of cerebrovascular flow in neonatal hypoxic-ischemic (HI) rats. Methods: Postnatal 7-day-old Sprague Dawley (SD) rats were divided into the control group, HI group, and hypoxia (H) group. TCD was applied to assess the changes of cerebral blood vessels, cerebrovascular flow velocity, and heart rate (HR) in sagittal and coronal sections at 1, 2, 3, and 7 days after the operation. For accuracy, cerebral infarct of rats was examined by 2,3,5-Triphenyl tetrazolium chloride (TTC) staining and Nissl staining to simultaneously verify the establishment of NHIE modeling. Results: Coronal and sagittal TCD scans revealed obvious alteration of cerebrovascular flow in main cerebral vessels. Obvious cerebrovascular back-flow was observed in anterior cerebral artery (ACA), basilar artery (BA), middle cerebral artery (MCA) of HI rats, along with accelerated cerebrovascular flows in the left internal carotid artery (ICA-L) and BA, decreased flows in right internal carotid artery (ICA-R) relative to those in the H and control groups. The alterations of cerebral blood flows in neonatal HI rats indicated successful ligation of right common carotid artery. Besides, TTC staining further validated the cerebral infarct was indeed caused due to ligation-induced insufficient blood supply. Damage to nervous tissues was also revealed by Nissl staining. Conclusion: Cerebral blood flow assessment by TCD in neonatal HI rats contributed to cerebrovascular abnormalities observed in a real-time and non-invasive way. The present study elicits the potentials to utilize TCD as an effective means for monitoring the progression of injury as well as NHIE modeling. The abnormal appearance of cerebral blood flow is also beneficial to the early warning and effective detection in clinical practice.

Silent infarction in sickle cell disease is associated with brain volume loss in excess of infarct volume.

Introduction: Sickle cell disease (SCD) increases cerebral infarct risk, but reported effects on brain volume have varied. More detailed information using larger cohorts and contemporary methods could motivate the use of longitudinal brain volume assessment in SCD as an automated marker of disease stability or future progression. The purpose of this study was to rigorously evaluate whether children and young adults with SCD have reduced gray matter volume (GMV) and white matter volume (WMV) compared to healthy controls using high-resolution MRI. We tested the hypotheses that (i) elevated CBF, a marker of cerebral hemodynamic compensation in SCD, is associated with global and regional brain atrophy, and (ii) silent cerebral infarct burden is associated with brain atrophy in excess of infarct volume. Methods: Healthy controls (n = 49) and SCD participants without overt stroke (n = 88) aged 7-32 years completed 3 T brain MRI; pseudocontinuous arterial spin labeling measured CBF. Multivariable linear regressions assessed associations of independent variables with GMV, WMV, and volumes of cortical/subcortical regions. Results: Reduced hemoglobin was associated with reductions in both GMV (p = 0.032) and WMV (p = 0.005); reduced arterial oxygen content (CaO2) was also associated with reductions in GMV (p = 0.035) and WMV (p = 0.006). Elevated gray matter CBF was associated with reduced WMV (p = 0.018). Infarct burden was associated with reductions in WMV 30-fold greater than the infarct volume itself (p = 0.005). Increased GM CBF correlated with volumetric reductions of the insula and left and right caudate nuclei (p = 0.017, 0.017, 0.036, respectively). Infarct burden was associated with reduced left and right nucleus accumbens, right thalamus, and anterior corpus callosum volumes (p = 0.002, 0.002, 0.009, 0.002, respectively). Discussion: We demonstrate that anemia and decreased CaO2 are associated with reductions in GMV and WMV in SCD. Increased CBF and infarct burden were also associated with reduced volume in subcortical structures. Global WMV deficits associated with infarct burden far exceed infarct volume itself. Hemodynamic compensation via increased cerebral blood flow in SCD seems inadequate to prevent brain volume loss. Our work highlights that silent cerebral infarcts are just a portion of the brain injury that occurs in SCD; brain volume is another potential biomarker of brain injury in SCD.

Stroke Recurrence and Antiplatelets in Posterior Versus Anterior Circulation Minor Stroke or Transient Ischemic Attack.

BACKGROUND: It is unclear whether infarct location affects stroke recurrence after index ischemic stroke. We aimed to compare the risk of stroke recurrence and the responses to dual antiplatelets with ticagrelor-aspirin versus clopidogrel-aspirin between patients with posterior circulation infarct (PCI) and those with anterior circulation infarct (ACI) after minor stroke or transient ischemic attack. METHODS: Data were obtained from the double-blind CHANCE-2 trial (Ticagrelor or Clopidogrel With Aspirin in High-Risk Patients With Acute Nondisabling Cerebrovascular Events II), which was conducted across 202 centers in China from September 2019 to March 2021. Patients with positive diffusion-weighted imaging were included and classified into PCI and ACI groups according to the hyperintense lesions on diffusion-weighted imaging. The primary efficacy and safety outcomes were a new stroke and severe or moderate bleeding within 90 days, respectively. RESULTS: A total of 4168 patients were included in this substudy, with 1427 PCI and 2741 ACI. During the 90-day follow-up, the risk of stroke recurrence in patients with PCI was similar to that with ACI (7.4% versus 8.3%; adjusted hazard ratio, 1.01 [95% CI, 0.79-1.29]; P=0.94). In comparison with clopidogrel-aspirin, ticagrelor-aspirin significantly reduced the risk of stroke recurrence in both the PCI (hazard ratio, 0.59 [95% CI, 0.40-0.89]; P=0.01) and ACI groups (hazard ratio, 0.65 [95% CI, 0.50-0.85]; P=0.002). There was no treatment-by-infarct location interaction (P value for interaction, 0.92). The risk of severe or moderate bleeding was similar between PCI and ACI patients (P=0.19). However, the risk of any bleeding increased on ticagrelor-aspirin than clopidogrel-aspirin treatment in PCI and ACI patients (P=0.02 and 0.002, respectively). CONCLUSIONS: Our study demonstrated that stroke recurrence was similar between PCI and ACI in patients with minor stroke or transient ischemic attack. Additionally, ticagrelor-aspirin was superior to clopidogrel-aspirin in reducing the risk of stroke within 90 days in both PCI and ACI patients. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT04078737.

Does TGFBR3 Polymorphism Increase the Risk of Silent Cerebral Infarction in Egyptian Children with Sickle Cell Disease?

OBJECTIVES: To evaluate the relationship between TGFBR3 rs284875 single nucleotide polymorphism (SNP) state and silent cerebral infarction (SCI) in asymptomatic patients with sickle cell disease (SCD). METHODS: A cross-sectional study was conducted on 50 children with SCD above 2 y of age followed up at the hematology outpatient clinic of Alexandria University Children's Hospital in Egypt. Twenty-four healthy children were included as a control group. All patients included in the study were subjected to complete history and clinical examination. Real-time polymerase chain reaction was performed on patients and controls for identification of SNP rs284875 of the TGFBR3 gene. A magnetic resonance imaging (MRI) of the brain were performed only on patients for detection of SCI. RESULTS: Fifty SCD patients were enrolled (26 males and 24 females), with a median age of 10.9 y (2.3-17.8 y), and 24 children as healthy control for the studied SNP. Thirty-five (70%) patients had homozygous SCD, while 30% had sickle ß-thalassemia. The brain MRI was normal in all the patients except for 2 patients who had features of SCI. The TGFBR3 rs284875 SNP was detected in 15 (30%) patients in the homozygous state (GG) versus only 1 (4.2%) child from the control group (p = 0.003). The prevalence of SCI was low in the study population and there was no statistically significant relationship between the TGFBR3 rs284875 SNP status and the presence of SCI in the brain MRI (p = 0.621). CONCLUSIONS: This study confirmed a low prevalence of SCI in the SCD patient included in the study. The TGFBR3 rs284875 SNP did not significantly increase SCI among those patients.

Assessment of silent brain injury in patients undergoing elective percutaneous coronary intervention due to chronic total occlusion.

Objective: Silent brain infarcts (SBI) are thromboembolic complications associated with cardiac surgery, diagnostic angiography, and percutaneous interventions. Serum neuron-specific enolase (NSE) is the proven biomarker for measuring neuronal damage. This study aimed to evaluate the incidence of SBI, defined as elevated NSE after coronary chronic total occlusion (CTO) intervention and elective coronary stenting. Design: The study population consisted of two patient groups: the CTO group included consecutive patients with coronary CTO intervention, and the control group consisted of patients who underwent elective coronary intervention. NSE blood levels were measured before and 12-18 h after the procedure. NSE blood levels of >20 ng/mL were considered SBI. Results: A total of 108 patients were included in the study. Of these, 55 (50.9%) had SBI after the procedure. The SBI rate was 59.7% in the CTO group and 39.1% in the control group. Patients with SBI were more likely to have diabetes mellitus, hyperlipidemia, higher HbA1c, higher total stent length, and longer procedural time. Multivariate logistic regression analysis showed that CTO procedure (odds ratio [OR]: 3.129; 95% confidence interval [CI]: 1.246-7.858; p < 0.015) and diabetes mellitus (OR: 2.93; 95% CI: 1.185-7.291; p < 0.020) are independent predictors of SBI. Conclusion: Our data suggest that SBI occurs more frequently after CTO intervention than after non-CTO intervention. Intervention complexity and patient clinical characteristics may explain the increased incidence.

Amelioration of Brain Damage after Treatment with the Methanolic Extract of Glycyrrhizae Radix et Rhizoma in Mice.

Glycyrrhizae Radix et Rhizoma (GR) is a traditional herbal medicine widely used in Asian countries. GR was the most frequently used medicine among stroke patients in Donguibogam, the most representative book in Korean medicine. In the present study, we investigated the neuroprotective effects of the GR methanolic extract (GRex) on an ischemic stroke mice model. Ischemic stroke was induced by a 90 min transient middle cerebral artery occlusion (MCAO), and GRex was administered to mice with oral gavage after reperfusion of MCA blood flow. The MCAO-induced edema and infarction volume was measured, and behavioral changes were evaluated by a novel object recognition test (NORT). Immunofluorescence stains and Western blotting identified underlying mechanisms of the protective effects of GRex. GRex post-treatment in mice with MCAO showed potent effects in reducing cerebral edema and infarction at 125 mg/kg but no effects when the dosage was much lower or higher than 125 mg/kg. GRex inhibited the decrease of spontaneous motor activity and novel object recognition functions. The neuroprotective effects of GRex on ischemic stroke were due to its regulation of inflammation-related neuronal cells, such as microglia and astrocytes.

Pituitary adenomas and cerebrovascular disease: A review on pathophysiology, prevalence, and treatment.

Pituitary adenomas (PAs) have been shown to cause excess cardiovascular disease comorbidity and mortality. Cerebrovascular disease (CeVD) is a small subset of cardiovascular disease with high morbidity, and its risk in patients with pituitary adenomas has been sparingly explored. In this review, we examine what is known about the prevalence of cerebrovascular disease in patients with PAs, from its initial discovery in 1970 to present. An abundance of literature describes increased cerebrovascular mortality in patients with acromegaly, while research on other PA subtypes is less frequent but shows a similarly elevated CeVD mortality relative to healthy populations. We also review how cerebrovascular risk changes after PAs are treated, with PA treatment appearing to prevent further accumulation of cerebrovascular risk without reversing prior elevations. While acromegaly-associated CeVD appears to be caused by elevated growth hormone (GH) levels and Cushing disease's elevated glucocorticoids similarly cause durable alterations in cerebrovascular structure and function, less is known about the mechanisms behind CeVD in other PA subpopulations. Proposed pathophysiologies include growth hormone deficiency inducing vessel wall damage or other hormone deficits causing increased atherosclerotic disease. Early diagnosis and treatment of PAs may be the key to minimizing lifetime CeVD risk elevations. More research is needed to better understand the mechanisms behind the increased CeVD seen in patients with PAs. Physicians caring for PA patients must remain vigilant for signs and symptoms of cerebrovascular disease in this patient population.