Leukoaraiosis is associated with clinical symptom severity, poor neurological function prognosis and stroke recurrence in mild intracerebral hemorrhage: a prospective multi-center cohort study

Intracerebral hemorrhage (ICH) refers to bleeding in the brain and is associated with the release of large amount of inflammasomes, and the activation of different cell death pathways. These cell death pathways lead to removal of inactivated and damaged cells and also result in neuronal cell damage. Pyroptosis is a newly discovered cell death pathway that has gained attention in recent years. This pathway mainly depends on activation of caspase-1-mediated cascades to cause cell death. We tested a well-known selective inhibitor of caspase-1, AC-YVAD-CMK, which has previously been found to have neuroprotective effects in ICH mice model, to ascertain its effects on the activation of inflammasomes mediated pyroptosis. Our results showed that AC-YVAD-CMK could reduce caspase-1 activation and inhibit IL-1β production and maturation, but has no effect on NLRP3 expression, an upstream inflammatory complex. AC-YVAD-CMK administration also resulted in reduction in M1-type microglia polarization around the hematoma, while increasing the number of M2-type cells. Furthermore, AC-YVAD-CMK treated mice showed some recovery of neurological function after hemorrhage especially at the hyperacute and subacute stage resulting in some degree of limb movement. In conclusion, we are of the view that AC-YVAD-CMK could inhibit pyroptosis, decrease the secretion or activation of inflammatory factors, and affect the polarization of microglia resulting in improvement of neurological function after ICH.

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Depressive symptoms in relation to clinical symptom onset of mild cognitive impairment

International Psychogeriatrics ◽

10.1017/s1041610218001138 ◽

2018 ◽

Vol 31 (04) ◽

pp. 561-569 ◽

Cited By ~ 2

Author(s):

Carol K. Chan ◽

Anja Soldan ◽

Corinne Pettigrew ◽

Mei-Cheng Wang ◽

Jiangxia Wang ◽

...

Keyword(s):

Cognitive Impairment ◽

Depressive Symptoms ◽

Mild Cognitive Impairment ◽

Clinical Symptom ◽

Symptom Onset ◽

Symptom Severity ◽

Hamilton Depression Scale ◽

Cognitively Normal ◽

Increased Risk ◽

Time To Onset

ABSTRACTObjective:There is increasing evidence of an association between depressive symptoms and mild cognitive impairment (MCI) in cross-sectional studies, but the longitudinal association between depressive symptoms and risk of MCI onset is less clear. The authors investigated whether baseline symptom severity of depression was predictive of time to onset of symptoms of MCI.Method:These analyses included 300 participants from the BIOCARD study, a cohort of individuals who were cognitively normal at baseline (mean age = 57.4 years) and followed for up to 20 years (mean follow-up = 2.5 years). Depression symptom severity was measured using the Hamilton Depression Scale (HAM-D). The authors assessed the association between dichotomous and continuous HAM-D and time to onset of MCI within 7 years versus after 7 years from baseline (reflecting the mean time from baseline to onset of clinical symptoms in the cohort) using Cox regression models adjusted for gender, age, and education.Results:At baseline, subjects had a mean HAM-D score of 2.2 (SD = 2.8). Higher baseline HAM-D scores were associated with an increased risk of progression from normal cognition to clinical symptom onset ≤ 7 years from baseline (p= 0.043), but not with progression > 7 years from baseline (p= 0.194). These findings remained significant after adjustment for baseline cognition.Conclusions:These results suggest that low levels of depressive symptoms may be predictive of clinical symptom onset within approximately 7 years among cognitively normal individuals and may be useful in identifying persons at risk for MCI due to Alzheimer’s disease.

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Risks of Stroke Recurrence and Mortality After First and Recurrent Strokes in Denmark: A Nationwide Registry Study

Neurology ◽

10.1212/wnl.0000000000013118 ◽

2021 ◽

pp. 10.1212/WNL.0000000000013118

Author(s):

Nils Skajaa ◽

Kasper Adelborg ◽

Erzsébet Horváth-Puhó ◽

Kenneth J Rothman ◽

Victor W. Henderson ◽

...

Keyword(s):

Ischemic Stroke ◽

Intracerebral Hemorrhage ◽

Risk Score ◽

Recurrent Stroke ◽

Recurrent Event ◽

Risk Scores ◽

Stroke Recurrence ◽

Stroke Severity ◽

Risk Of Death ◽

First Time

Background and Objectives:To examine risks of stroke recurrence and mortality after first and recurrent stroke.Methods:Using Danish nationwide health registries, we included patients (age ≥18 years) with first-time ischemic stroke (N = 105,397) or intracerebral hemorrhage (N = 13,350) during 2004–2018. Accounting for the competing risk of death, absolute risks of stroke recurrence were computed separately for each stroke subtype and within strata of age groups, sex, stroke severity, body mass index, smoking, alcohol, the Essen stroke risk score, and atrial fibrillation. Mortality risks were computed after first and recurrent stroke.Results:After adjusting for competing risks, the overall 1-year and 10-year risks of recurrence were 4% and 13% following first-time ischemic stroke and 3% and 12% following first-time intracerebral hemorrhage. For ischemic stroke, the risk of recurrence increased with age, was higher for men and following mild than more severe stroke. The most marked differences were across Essen risk scores, for which recurrence risks increased with increasing scores. For intracerebral hemorrhage, risks were similar for both sexes and did not increase with Essen risk score. For ischemic stroke, the 1-year and 10-year risks of all-cause mortality were 17% and 56% after a first-time stroke and 25% and 70% after a recurrent stroke; corresponding estimates for intracerebral hemorrhage were 37% and 70% after a first-time event and 31% and 75% after a recurrent event.Conclusion:The risk of stroke recurrence was substantial following both subtypes, but risks differed markedly among patient subgroups. The risk of mortality was higher after a recurrent than first-time stroke.

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Higher Risk of Ischemic Stroke After an Intracerebral Hemorrhage Than in General Population: A Cohort Study From the United Kingdom

Stroke ◽

10.1161/strokeaha.121.037633 ◽

2021 ◽

Author(s):

David Gaist ◽

Antonio Gonzáléz-Pérez ◽

Stine Munk Hald ◽

Luis Alberto García Rodríguez

Keyword(s):

Cohort Study ◽

United Kingdom ◽

Ischemic Stroke ◽

General Population ◽

Intracerebral Hemorrhage ◽

The United Kingdom

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USING THE CHA2DS2-VASC SCORE TO PREDICT ISCHEMIC STROKE IN PATIENTS WITH INTRACEREBRAL HEMORRHAGE: A NATIONWIDE COHORT STUDY

Journal of the American College of Cardiology ◽

10.1016/s0735-1097(19)31111-8 ◽

2019 ◽

Vol 73 (9) ◽

pp. 503

Author(s):

Peter Brønnum Nielsen ◽

Thure Filskov Overvad ◽

Flemming Skjøth ◽

Søren Due Andersen ◽

Mette Søgaard ◽

...

Keyword(s):

Cohort Study ◽

Ischemic Stroke ◽

Intracerebral Hemorrhage

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Ac-YVAD-cmk improves neurological function by inhibiting caspase-1-mediated inflammatory response in the intracerebral hemorrhage of rats

International Immunopharmacology ◽

10.1016/j.intimp.2019.105771 ◽

2019 ◽

Vol 75 ◽

pp. 105771 ◽

Cited By ~ 1

Author(s):

Hongsheng Liang ◽

Yong Sun ◽

Aili Gao ◽

Nannan Zhang ◽

Ying Jia ◽

...

Keyword(s):

Inflammatory Response ◽

Intracerebral Hemorrhage ◽

Neurological Function ◽

Caspase 1

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The Possible Inhibition Effect of Lycium barbarum Polysaccharides on Rat Intracerebral Hemorrhage Secondary Neuronal Apoptosis through Intervening Endogenous/Exogenous Pathways of Apoptosis

Indian Journal of Neurosurgery ◽

10.1055/s-0040-1713059 ◽

2020 ◽

Vol 9 (02) ◽

pp. 106-114

Author(s):

Yourui Zou ◽

ShengYu Sun ◽

Usama Ilyas Sharif ◽

Abdul Wasie ◽

Hui Ma

Keyword(s):

Intracerebral Hemorrhage ◽

Neuronal Apoptosis ◽

B Cell Lymphoma ◽

Neurological Function ◽

Terminal Deoxynucleotidyl Transferase ◽

Sham Operation ◽

Lycium Barbarum ◽

Inhibition Effect ◽

The Impact ◽

Lycium Barbarum Polysaccharides

Abstract Objective The aim of this study was to explore the inhibition effect and possible mechanism of Lycium barbarum polysaccharides (LBP) on rat intracerebral hemorrhage (ICH) secondary neuronal apoptosis. Materials and Methods High-, medium-, and low-dose LBP (50, 100, and 200 mg•kg) and nimodipine (10 mg•kg) groups were given once daily by 15-day gavage before operation, while the sham operation and ICH groups were given the equal volume of saline. An ICH model was established by autologous blood injection and the neurological function in each group was scored at 4, 8, 12, 24, and 48 hours after modeling. Furthermore, terminal deoxynucleotidyl transferase dUTP nick end labeling analysis was performed to detect neuronal apoptosis, while western blot, immunohistochemistry, and real-time-polymerase chain reaction were used to study the influence of LBP on ICH secondary neuronal apoptosis. Results The neurological function score was significantly decreased after ICH, and the intervention effect of a single drug was not evident. The apoptotic nerve cells increased significantly in the ICH group but decreased considerably in the LBP groups. Furthermore, tumor necrosis factor alpha (TNF-α) expression decreased significantly, while B-cell lymphoma 2 expression increased substantially in the high- and medium-dose LBP groups compared with ICH group, suggesting that LBP could reduce the effect of ICH. However, the impact of LBP did not correlate positively with the dose. Conclusion The application of LBP may not significantly improve neurological function after ICH, but it can inhibit rat ICH secondary neuronal apoptosis.

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