Browsing by Subject "Cerebral Hemorrhage"
Now showing 1 - 15 of 15
Results Per Page
Sort Options
Item Open Access A risk score for in-hospital death in patients admitted with ischemic or hemorrhagic stroke.(J Am Heart Assoc, 2013-01-28) Smith, Eric E; Shobha, Nandavar; Dai, David; Olson, DaiWai M; Reeves, Mathew J; Saver, Jeffrey L; Hernandez, Adrian F; Peterson, Eric D; Fonarow, Gregg C; Schwamm, Lee HBACKGROUND: We aimed to derive and validate a single risk score for predicting death from ischemic stroke (IS), intracerebral hemorrhage (ICH), and subarachnoid hemorrhage (SAH). METHODS AND RESULTS: Data from 333 865 stroke patients (IS, 82.4%; ICH, 11.2%; SAH, 2.6%; uncertain type, 3.8%) in the Get With The Guidelines-Stroke database were used. In-hospital mortality varied greatly according to stroke type (IS, 5.5%; ICH, 27.2%; SAH, 25.1%; unknown type, 6.0%; P<0.001). The patients were randomly divided into derivation (60%) and validation (40%) samples. Logistic regression was used to determine the independent predictors of mortality and to assign point scores for a prediction model in the overall population and in the subset with the National Institutes of Health Stroke Scale (NIHSS) recorded (37.1%). The c statistic, a measure of how well the models discriminate the risk of death, was 0.78 in the overall validation sample and 0.86 in the model including NIHSS. The model with NIHSS performed nearly as well in each stroke type as in the overall model including all types (c statistics for IS alone, 0.85; for ICH alone, 0.83; for SAH alone, 0.83; uncertain type alone, 0.86). The calibration of the model was excellent, as demonstrated by plots of observed versus predicted mortality. CONCLUSIONS: A single prediction score for all stroke types can be used to predict risk of in-hospital death following stroke admission. Incorporation of NIHSS information substantially improves this predictive accuracy.Item Open Access Anticoagulation in Acute Neurological Disease.(Seminars in neurology, 2021-10) Sasannejad, Cina; Sheth, Kevin NWhile anticoagulation and its reversal have been of clinical relevance for decades, recent academic and technological advances have expanded the repertoire of its application in neurological disease. The advent of direct oral anticoagulants provides effective, mechanistically elegant, and relatively safer therapeutic options than warfarin for eligible patients at risk for neurological sequelae of prothrombotic states, particularly given the recent availability of corresponding reversal agents. In this review, we examine the provenance, indications, safety, and reversal tools for anticoagulant medications in the context of neurological disease, with specific attention to acute ischemic stroke, cerebral venous sinus thrombosis, and intracerebral hemorrhage. We will use specific clinical scenarios to illustrate the complex factors that must be considered in the use of anticoagulation, including intracranial pathology such as intracerebral hemorrhage, traumatic brain injury, or malignancy; metabolic complications such as chronic kidney disease; pregnancy; and advanced age.Item Open Access Association of Intracerebral Hemorrhage Among Patients Taking Non-Vitamin K Antagonist vs Vitamin K Antagonist Oral Anticoagulants With In-Hospital Mortality.(JAMA, 2018-02) Inohara, Taku; Xian, Ying; Liang, Li; Matsouaka, Roland A; Saver, Jeffrey L; Smith, Eric E; Schwamm, Lee H; Reeves, Mathew J; Hernandez, Adrian F; Bhatt, Deepak L; Peterson, Eric D; Fonarow, Gregg CAlthough non-vitamin K antagonist oral anticoagulants (NOACs) are increasingly used to prevent thromboembolic disease, there are limited data on NOAC-related intracerebral hemorrhage (ICH).To assess the association between preceding oral anticoagulant use (warfarin, NOACs, and no oral anticoagulants [OACs]) and in-hospital mortality among patients with ICH.Retrospective cohort study of 141 311 patients with ICH admitted from October 2013 to December 2016 to 1662 Get With The Guidelines-Stroke hospitals.Anticoagulation therapy before ICH, defined as any use of OACs within 7 days prior to hospital arrival.In-hospital mortality.Among 141 311 patients with ICH (mean [SD] age, 68.3 [15.3] years; 48.1% women), 15 036 (10.6%) were taking warfarin and 4918 (3.5%) were taking NOACs preceding ICH, and 39 585 (28.0%) and 5783 (4.1%) were taking concomitant single and dual antiplatelet agents, respectively. Patients with prior use of warfarin or NOACs were older and had higher prevalence of atrial fibrillation and prior stroke. Acute ICH stroke severity (measured by the National Institutes of Health Stroke Scale) was not significantly different across the 3 groups (median, 9 [interquartile range, 2-21] for warfarin, 8 [2-20] for NOACs, and 8 [2-19] for no OACs). The unadjusted in-hospital mortality rates were 32.6% for warfarin, 26.5% for NOACs, and 22.5% for no OACs. Compared with patients without prior use of OACs, the risk of in-hospital mortality was higher among patients with prior use of warfarin (adjusted risk difference [ARD], 9.0% [97.5% CI, 7.9% to 10.1%]; adjusted odds ratio [AOR], 1.62 [97.5% CI, 1.53 to 1.71]) and higher among patients with prior use of NOACs (ARD, 3.3% [97.5% CI, 1.7% to 4.8%]; AOR, 1.21 [97.5% CI, 1.11-1.32]). Compared with patients with prior use of warfarin, patients with prior use of NOACs had a lower risk of in-hospital mortality (ARD, -5.7% [97.5% CI, -7.3% to -4.2%]; AOR, 0.75 [97.5% CI, 0.69 to 0.81]). The difference in mortality between NOAC-treated patients and warfarin-treated patients was numerically greater among patients with prior use of dual antiplatelet agents (32.7% vs 47.1%; ARD, -15.0% [95.5% CI, -26.3% to -3.8%]; AOR, 0.50 [97.5% CI, 0.29 to 0.86]) than among those taking these agents without prior antiplatelet therapy (26.4% vs 31.7%; ARD, -5.0% [97.5% CI, -6.8% to -3.2%]; AOR, 0.77 [97.5% CI, 0.70 to 0.85]), although the interaction P value (.07) was not statistically significant.Among patients with ICH, prior use of NOACs or warfarin was associated with higher in-hospital mortality compared with no OACs. Prior use of NOACs, compared with prior use of warfarin, was associated with lower risk of in-hospital mortality.Item Open Access Bone Marrow Mesenchymal Stem Cell Transplantation Increases GAP-43 Expression via ERK1/2 and PI3K/Akt Pathways in Intracerebral Hemorrhage.(Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology, 2017-01) Cui, Jianzhong; Cui, Changmeng; Cui, Ying; Li, Ran; Sheng, Huaxin; Jiang, Xiaohua; Tian, Yanxia; Wang, Kaijie; Gao, JunlingBackground/aims
Intracerebral hemorrhage (ICH) occurs in hypertensive patients and results in high rates of mortality and disability. This study determined whether bone marrow mesenchymal stem cell (BMSC) transplantation affects axonal regeneration and examined the underlying mechanisms after the administration of PD98059 (p-ERK1/2 inhibitor) or/ and LY294002 (PI3K inhibitor). The hypothesis that was intended to be tested was that BMSC transplantation regulates the expression of growth-associated protein-43 (GAP-43) via the ERK1/2 and PI3K/Akt signaling pathways.Methods
Seventy-five male rats (250-280 g) were subjected to intracerebral blood injection and then randomly received a vehicle, BMSCs, PD98059 or LY294002 treatment. Neurological deficits were evaluated prior to injury and at 1, 3 and 7 days post-injury. The expression of GAP-43, Akt, p-Akt, ERK1/2, and p-ERK1/2 proteins was measured by western blot analysis.Results
BMSC transplantation attenuated neurological deficits 3-7 days post-ICH. The expression of GAP-43 was increased 3 days following BMSC transplantation. However, this increase was inhibited by either PD98059 or LY294002 treatment. Treatment with both PD98059 and LY294002 was more effective than was treatment with an individual compound.Conclusion
BMSC transplantation could attenuate neurological deficits and activate axonal regeneration in this rat ICH model. The protective effects might be associated with increased GAP-43 expression by activating both the ERK1/2 and PI3K/Akt signaling pathways.Item Open Access Clinician judgment vs formal scales for predicting intracerebral hemorrhage outcomes.(Neurology, 2016-01-12) Hwang, David Y; Dell, Cameron A; Sparks, Mary J; Watson, Tiffany D; Langefeld, Carl D; Comeau, Mary E; Rosand, Jonathan; Battey, Thomas WK; Koch, Sebastian; Perez, Mario L; James, Michael L; McFarlin, Jessica; Osborne, Jennifer L; Woo, Daniel; Kittner, Steven J; Sheth, Kevin NOBJECTIVE: To compare the performance of formal prognostic instruments vs subjective clinical judgment with regards to predicting functional outcome in patients with spontaneous intracerebral hemorrhage (ICH). METHODS: This prospective observational study enrolled 121 ICH patients hospitalized at 5 US tertiary care centers. Within 24 hours of each patient's admission to the hospital, one physician and one nurse on each patient's clinical team were each asked to predict the patient's modified Rankin Scale (mRS) score at 3 months and to indicate whether he or she would recommend comfort measures. The admission ICH score and FUNC score, 2 prognostic scales selected for their common use in neurologic practice, were calculated for each patient. Spearman rank correlation coefficients (r) with respect to patients' actual 3-month mRS for the physician and nursing predictions were compared against the same correlation coefficients for the ICH score and FUNC score. RESULTS: The absolute value of the correlation coefficient for physician predictions with respect to actual outcome (0.75) was higher than that of either the ICH score (0.62, p = 0.057) or the FUNC score (0.56, p = 0.01). The nursing predictions of outcome (r = 0.72) also trended towards an accuracy advantage over the ICH score (p = 0.09) and FUNC score (p = 0.03). In an analysis that excluded patients for whom comfort care was recommended, the 65 available attending physician predictions retained greater accuracy (r = 0.73) than either the ICH score (r = 0.50, p = 0.02) or the FUNC score (r = 0.42, p = 0.004). CONCLUSIONS: Early subjective clinical judgment of physicians correlates more closely with 3-month outcome after ICH than prognostic scales.Item Open Access Diffuse white matter loss in a transgenic rat model of cerebral amyloid angiopathy.(Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism, 2021-05) Lee, Hedok; Xu, Feng; Liu, Xiaodan; Koundal, Sunil; Zhu, Xiaoyue; Davis, Judianne; Yanez, David; Schrader, Joseph; Stanisavljevic, Aleksandra; Rothman, Douglas L; Wardlaw, Joanna; Van Nostrand, William E; Benveniste, HeleneDiffuse white matter (WM) disease is highly prevalent in elderly with cerebral small vessel disease (cSVD). In humans, cSVD such as cerebral amyloid angiopathy (CAA) often coexists with Alzheimer's disease imposing a significant impediment for characterizing their distinct effects on WM. Here we studied the burden of age-related CAA pathology on WM disease in a novel transgenic rat model of CAA type 1 (rTg-DI). A cohort of rTg-DI and wild-type rats was scanned longitudinally using MRI for characterization of morphometry, cerebral microbleeds (CMB) and WM integrity. In rTg-DI rats, a distinct pattern of WM loss was observed at 9 M and 11 M. MRI also revealed manifestation of small CMB in thalamus at 6 M, which preceded WM loss and progressively enlarged until the moribund disease stage. Histology revealed myelin loss in the corpus callosum and thalamic CMB in all rTg-DI rats, the latter of which manifested in close proximity to occluded and calcified microvessels. The quantitation of CAA load in rTg-DI rats revealed that the most extensive microvascular Aβ deposition occurred in the thalamus. For the first time using in vivo MRI, we show that CAA type 1 pathology alone is associated with a distinct pattern of WM loss.Item Open Access Gender and age interact to affect early outcome after intracerebral hemorrhage.(PLoS One, 2013) Umeano, Odera; Phillips-Bute, Barbara; Hailey, Claire E; Sun, Wei; Gray, Marisa C; Roulhac-Wilson, Briana; McDonagh, David L; Kranz, Peter G; Laskowitz, Daniel T; James, Michael LBACKGROUND: Intracerebral hemorrhage (ICH) is a common and devastating form of cerebrovascular disease. In ICH, gender differences in outcomes remain relatively understudied but have been examined in other neurological emergencies. Further, a potential effect of age and gender on outcomes after ICH has not been explored. This study was designed to test the hypothesis that age and gender interact to modify neurological outcomes after ICH. METHODS: Adult patients admitted with spontaneous primary supratentorial ICH from July 2007 through April 2010 were assessed via retrospective analysis of an existing stroke database at Duke University. Univariate analysis of collected variables was used to compare gender and outcome. Unfavorable outcome was defined as discharge to hospice or death. Using multivariate regression, the combined effect of age and gender on outcome after ICH was analyzed. RESULTS: In this study population, women were younger (61.1+14.5 versus 65.8+17.3 years, p=0.03) and more likely to have a history of substance abuse (35% versus 8.9%, p<0.0001) compared to men. Multivariable models demonstrated that advancing age had a greater effect on predicting discharge outcome in women compared to men (p=0.02). For younger patients, female sex was protective; however, at ages greater than 60 years, female sex was a risk factor for discharge to hospice or death. CONCLUSION: While independently associated with discharge to hospice or death after ICH, the interaction effect between gender and age demonstrated significantly stronger correlation with early outcome after ICH in a single center cohort. Prospective study is required to verify these findings.Item Open Access Incontinence and gait disturbance after intraventricular extension of intracerebral hemorrhage.(Neurology, 2016-03-08) Woo, Daniel; Kruger, Andrew J; Sekar, Padmini; Haverbusch, Mary; Osborne, Jennifer; Moomaw, Charles J; Martini, Sharyl; Hosseini, Shahla M; Ferioli, Simona; Worrall, Bradford B; Elkind, Mitchell SV; Sung, Gene; James, Michael L; Testai, Fernando D; Langefeld, Carl D; Broderick, Joseph P; Koch, Sebastian; Flaherty, Matthew LOBJECTIVE: We tested the hypothesis that intraventricular hemorrhage (IVH) is associated with incontinence and gait disturbance among survivors of intracerebral hemorrhage (ICH) at 3-month follow-ups. METHODS: The Genetic and Environmental Risk Factors for Hemorrhagic Stroke study was used as the discovery set. The Ethnic/Racial Variations of Intracerebral Hemorrhage study served as a replication set. Both studies performed prospective hot-pursuit recruitment of ICH cases with 3-month follow-up. Multivariable logistic regression analyses were computed to identify risk factors for incontinence and gait dysmobility at 3 months after ICH. RESULTS: The study population consisted of 307 ICH cases in the discovery set and 1,374 cases in the replication set. In the discovery set, we found that increasing IVH volume was associated with incontinence (odds ratio [OR] 1.50; 95% confidence interval [CI] 1.10-2.06) and dysmobility (OR 1.58; 95% CI 1.17-2.15) after controlling for ICH location, initial ICH volume, age, baseline modified Rankin Scale score, sex, and admission Glasgow Coma Scale score. In the replication set, increasing IVH volume was also associated with both incontinence (OR 1.42; 95% CI 1.27-1.60) and dysmobility (OR 1.40; 95% CI 1.24-1.57) after controlling for the same variables. CONCLUSION: ICH subjects with IVH extension are at an increased risk for developing incontinence and dysmobility after controlling for factors associated with severity and disability. This finding suggests a potential target to prevent or treat long-term disability after ICH with IVH.Item Open Access Intrastriatal injection of autologous blood or clostridial collagenase as murine models of intracerebral hemorrhage.(Journal of visualized experiments : JoVE, 2014-07-03) Lei, Beilei; Sheng, Huaxin; Wang, Haichen; Lascola, Christopher D; Warner, David S; Laskowitz, Daniel T; James, Michael LIntracerebral hemorrhage (ICH) is a common form of cerebrovascular disease and is associated with significant morbidity and mortality. Lack of effective treatment and failure of large clinical trials aimed at hemostasis and clot removal demonstrate the need for further mechanism-driven investigation of ICH. This research may be performed through the framework provided by preclinical models. Two murine models in popular use include intrastriatal (basal ganglia) injection of either autologous whole blood or clostridial collagenase. Since, each model represents distinctly different pathophysiological features related to ICH, use of a particular model may be selected based on what aspect of the disease is to be studied. For example, autologous blood injection most accurately represents the brain's response to the presence of intraparenchymal blood, and may most closely replicate lobar hemorrhage. Clostridial collagenase injection most accurately represents the small vessel rupture and hematoma evolution characteristic of deep hemorrhages. Thus, each model results in different hematoma formation, neuroinflammatory response, cerebral edema development, and neurobehavioral outcomes. Robustness of a purported therapeutic intervention can be best assessed using both models. In this protocol, induction of ICH using both models, immediate post-operative demonstration of injury, and early post-operative care techniques are demonstrated. Both models result in reproducible injuries, hematoma volumes, and neurobehavioral deficits. Because of the heterogeneity of human ICH, multiple preclinical models are needed to thoroughly explore pathophysiologic mechanisms and test potential therapeutic strategies.Item Open Access Long-term chemogenetic activation of M1 glutamatergic neurons attenuates the behavioral and cognitive deficits caused by intracerebral hemorrhage.(Biochemical and biophysical research communications, 2020-06) Ling, Wen-Yuan; Cui, Ying; Gao, Jun-Ling; Jiang, Xiao-Hua; Wang, Kai-Jie; Tian, Yan-Xia; Sheng, Hua-Xin; Cui, Jian-ZhongAcute spontaneous intracerebral hemorrhage (ICH) is a life-threatening disease. It is often accompanied by severe neurological sequelae largely caused by the loss of integrity of the neural circuits. However, these neurological sequelae have few strong medical interventions. Designer receptors exclusively activated by designer drugs (DREADDs) are important chemogenetic tools capable of precisely modulating the activity of neural circuits. They have been suggested to have therapeutic effects on multiple neurological diseases. Despite this, no empirical research has explored the effects of DREADDs on functional recovery after ICH. We aimed to explore whether the long-term excitation of glutamatergic neurons in primary motor cortex (M1) by DREADD could promote functional recovery after ICH. We used CaMKII-driven Gq/Gi-DREADDs to activate/inhibit M1 glutamatergic neurons for 21 consecutive days, and examined their effects on behavioral and cognitive deficits caused by ICH in a mouse model of ICH targeting striatum. Long-term chemogenetic activation of the M1 glutamatergic neurons increased the spatial memory and sensorimotor ability of mice suffering from ICH. It also attenuated the mitochondrial dysfunctions of striatal neurons by raising the ATP levels and mitochondrial membrane potential while decreasing the 8-OHdG levels. These results strongly suggest that selective stimulation of the M1 glutamatergic neurons contributes to functional recovery after ICH presumably through alleviation of mitochondrial dysfunctions.Item Open Access Ratios of head circumference to ventricular size vary over time and predict eventual need for CSF diversion in intraventricular hemorrhage of prematurity.(Child's nervous system : ChNS : official journal of the International Society for Pediatric Neurosurgery, 2024-03) Venkatraman, Vishal; Harward, Stephen C; Bhasin, Srijan; Calderon, Kylie; Atkins, Sage L; Liu, Beiyu; Lee, Hui-Jie; Chow, Shein-Chung; Fuchs, Herbert E; Thompson, Eric MPurpose
Intraventricular hemorrhage (IVH) of prematurity can lead to hydrocephalus, sometimes necessitating permanent cerebrospinal fluid (CSF) diversion. We sought to characterize the relationship between head circumference (HC) and ventricular size in IVH over time to evaluate the clinical utility of serial HC measurements as a metric in determining the need for CSF diversion.Methods
We included preterm infants with IVH born between January 2000 and May 2020. Three measures of ventricular size were obtained: ventricular index (VI), Evan's ratio (ER), and frontal occipital head ratio (FOHR). The Pearson correlations (r) between the initial (at birth) paired measurements of HC and ventricular size were reported. Multivariable longitudinal regression models were fit to examine the HC:ventricle size ratio, adjusting for the age of the infant, IVH grade (I/II vs. III/IV), need for CSF diversion, and sex.Results
A total of 639 patients with an average gestational age of 27.5 weeks were included. IVH grade I/II and grade III/IV patients had a positive correlation between initial HC and VI (r = 0.47, p < 0.001 and r = 0.48, p < 0.001, respectively). In our longitudinal models, patients with a low-grade IVH (I/II) had an HC:VI ratio 0.52 higher than those with a high-grade IVH (p-value < 0.001). Patients with low-grade IVH had an HC:ER ratio 12.94 higher than those with high-grade IVH (p-value < 0.001). Patients with low-grade IVH had a HC:FOHR ratio 12.91 higher than those with high-grade IVH (p-value < 0.001). Infants who did not require CSF diversion had an HC:VI ratio 0.47 higher than those who eventually did (p < 0.001). Infants without CSF diversion had an HC:ER ratio 16.53 higher than those who received CSF diversion (p < 0.001). Infants without CSF diversion had an HC:FOHR ratio 15.45 higher than those who received CSF diversion (95% CI (11.34, 19.56), p < 0.001).Conclusions
There is a significant difference in the ratio of HC:VI, HC:ER, and HC:FOHR size between patients with high-grade IVH and low-grade IVH. Likewise, there is a significant difference in HC:VI, HC:ER, and HC:FOHR between those who did and did not have CSF diversion. The routine assessments of both head circumference and ventricle size by ultrasound are important clinical tools in infants with IVH of prematurity.Item Open Access Risks and Benefits Associated With Prestroke Antiplatelet Therapy Among Patients With Acute Ischemic Stroke Treated With Intravenous Tissue Plasminogen Activator.(JAMA neurology, 2016-01) Xian, Ying; Federspiel, Jerome J; Grau-Sepulveda, Maria; Hernandez, Adrian F; Schwamm, Lee H; Bhatt, Deepak L; Smith, Eric E; Reeves, Mathew J; Thomas, Laine; Webb, Laura; Bettger, Janet Prvu; Laskowitz, Daniel T; Fonarow, Gregg C; Peterson, Eric DIntravenous tissue plasminogen activator (tPA) is known to improve outcomes in ischemic stroke; however, many patients may have been receiving antiplatelet therapy before acute ischemic stroke and could face an increased risk for bleeding when treated with tPA.To assess the risks and benefits associated with prestroke antiplatelet therapy among patients with ischemic stroke who receive intravenous tPA.This observational study used data from the American Heart Association and American Stroke Association Get With the Guidelines-Stroke registry, which included 85 072 adult patients with ischemic stroke who received intravenous tPA in 1545 registry hospitals from January 1, 2009, through March 31, 2015. Data were analyzed during the same period.Prestroke antiplatelet therapy before tPA administration for acute ischemic stroke.Symptomatic intracranial hemorrhage (sICH), in-hospital mortality, discharge ambulatory status, and modified Rankin Scale score (range, 0 [no symptoms] to 6 [death]).Of the 85 072 registry patients, 38 844 (45.7%) were receiving antiplatelet therapy before admission; 46 228 patients (54.3%) were not. Patients receiving antiplatelet therapy were older (median [25th-75th percentile] age, 76 [65-84] vs 68 [56-80] years) and had a higher prevalence of cardiovascular risk factors. The unadjusted rate of sICH was higher in patients receiving antiplatelet therapy (5.0% vs 3.7%). After risk adjustment, prior use of antiplatelet agents remained associated with higher odds of sICH compared with no use (adjusted odds ratio [AOR], 1.18 [95% CI, 1.10-1.28]; absolute difference, +0.68% [95% CI, 0.36%-1.01%]; number needed to harm [NNH], 147). Among patients enrolled on October 1, 2012, or later, the highest odds (95% CIs) of sICH were found in 15 116 patients receiving aspirin alone (AOR, 1.19 [1.06- 1.34]; absolute difference [95% CI], +0.68% [0.21%-1.20%]; NNH, 147) and 2397 patients receiving dual antiplatelet treatment of aspirin and clopidogrel (AOR, 1.47 [1.16-1.86]; absolute difference, +1.67% [0.58%-3.00%]; NNH, 60). The risk for in-hospital mortality was similar between those who were and were not receiving antiplatelet therapy after adjustment (8.0% vs 6.6%; AOR, 1.00 [0.94-1.06]; nonsignificant absolute difference, -0.01% [-0.37% to 0.36%]). However, patients receiving antiplatelet therapy had a greater risk-adjusted likelihood of independent ambulation (42.1% vs 46.6%; AOR, 1.13 [1.08-1.17]; absolute difference, +2.23% [1.55%-2.92%]; number needed to treat, 43) and better functional outcomes (modified Rankin Scale score, 0-1) at discharge (24.1% vs 27.8%; AOR, 1.14; 1.07-1.22; absolute difference, +1.99% [0.78%-3.22%]; number needed to treat, 50).Among patients with an acute ischemic stroke treated with intravenous tPA, those receiving antiplatelet therapy before the stroke had a higher risk for sICH but better functional outcomes than those who were not receiving antiplatelet therapy.Item Open Access Sex-Specific Effects of Progesterone on Early Outcome of Intracerebral Hemorrhage.(Neuroendocrinology, 2016-01) Hsieh, Justin T; Lei, Beilei; Sheng, Huaxin; Venkatraman, Talagnair; Lascola, Christopher D; Warner, David S; James, Michael LBackground
Preclinical evidence suggests that progesterone improves recovery after intracerebral hemorrhage (ICH); however, gonadal hormones have sex-specific effects. Therefore, an experimental model of ICH was used to assess recovery after progesterone administration in male and female rats.Methods
ICH was induced in male and female Wistar rats via stereotactic intrastriatal injection of clostridial collagenase (0.5 U). Animals were randomized to receive vehicle or 8 mg/kg progesterone intraperitoneally at 2 h, then subcutaneously at 5, 24, 48, and 72 h after injury. Outcomes included relevant physiology during the first 3 h, hemorrhage and edema evolution over the first 24 h, proinflammatory transcription factor and cytokine regulation at 24 h, rotarod latency and neuroseverity score over the first 7 days, and microglial activation/macrophage recruitment at 7 days after injury.Results
Rotarod latency (p = 0.001) and neuroseverity score (p = 0.01) were improved in progesterone-treated males, but worsened in progesterone-treated females (p = 0.028 and p = 0.008, respectively). Progesterone decreased cerebral edema (p = 0.04), microglial activation/macrophage recruitment (p < 0.001), and proinflammatory transcription factor phosphorylated nuclear factor-x03BA;B p65 expression (p = 0.0038) in males but not females, independent of tumor necrosis factor-α, interleukin-6, and toll-like receptor-4 expression. Cerebral perfusion was increased in progesterone-treated males at 4 h (p = 0.043) but not 24 h after injury. Hemorrhage volume, arterial blood gases, glucose, and systolic blood pressure were not affected.Conclusions
Progesterone administration improved early neurobehavioral recovery and decreased secondary neuroinflammation after ICH in male rats. Paradoxically, progesterone worsened neurobehavioral recovery and did not modify neuroinflammation in female rats. Future work should isolate mechanisms of sex-specific progesterone effects after ICH.Item Open Access Tumor necrosis factor α antagonism improves neurological recovery in murine intracerebral hemorrhage.(J Neuroinflammation, 2013-08-20) Lei, Beilei; Dawson, Hana N; Roulhac-Wilson, Briana; Wang, Haichen; Laskowitz, Daniel T; James, Michael LBACKGROUND: Intracerebral hemorrhage (ICH) is a devastating stroke subtype characterized by a prominent neuroinflammatory response. Antagonism of pro-inflammatory cytokines by specific antibodies represents a compelling therapeutic strategy to improve neurological outcome in patients after ICH. To test this hypothesis, the tumor necrosis factor alpha (TNF-α) antibody CNTO5048 was administered to mice after ICH induction, and histological and functional endpoints were assessed. METHODS: Using 10 to 12-week-old C57BL/6J male mice, ICH was induced by collagenase injection into the left basal ganglia. Brain TNF-α concentration, microglia activation/macrophage recruitment, hematoma volume, cerebral edema, and rotorod latency were assessed in mice treated with the TNF-α antibody, CNTO5048, or vehicle. RESULTS: After ICH induction, mice treated with CNTO5048 demonstrated reduction in microglial activation/macrophage recruitment compared to vehicle-treated animals, as assessed by unbiased stereology (P = 0.049). This reduction in F4/80-positive cells was associated with a reduction in cleaved caspase-3 (P = 0.046) and cerebral edema (P = 0.026) despite similar hematoma volumes, when compared to mice treated with vehicle control. Treatment with CNTO5048 after ICH induction was associated with a reduction in functional deficit when compared to mice treated with vehicle control, as assessed by rotorod latencies (P = 0.024). CONCLUSIONS: Post-injury treatment with the TNF-α antibody CNTO5048 results in less neuroinflammation and improved functional outcomes in a murine model of ICH.Item Open Access Xenon neuroprotection in experimental stroke: interactions with hypothermia and intracerebral hemorrhage.(Anesthesiology, 2012-12) Sheng, Siyuan P; Lei, Beilei; James, Michael L; Lascola, Christopher D; Venkatraman, Talaignair N; Jung, Jin Yong; Maze, Mervyn; Franks, Nicholas P; Pearlstein, Robert D; Sheng, Huaxin; Warner, David SBackground
Xenon has been proven to be neuroprotective in experimental brain injury. The authors hypothesized that xenon would improve outcome from focal cerebral ischemia with a delayed treatment onset and prolonged recovery interval.Methods
Rats were subjected to 70 min temporary focal ischemia. Ninety minutes later, rats were treated with 0, 15, 30, or 45% Xe for 20 h or 0 or 30% Xe for 8, 20, or 44 h. Outcome was measured after 7 days. In another experiment, after ischemia, rats were maintained at 37.5° or 36.0°C for 20 h with or without 30% Xe. Outcome was assessed 28 days later. Finally, mice were subjected to intracerebral hemorrhage with or without 30% Xe for 20 h. Brain water content, hematoma volume, rotarod function, and microglial activation were measured.Results
Cerebral infarct sizes (mean±SD) for 0, 15, 30, and 45% Xe were 212±27, 176±55, 160±32, and 198±54 mm, respectively (P=0.023). Neurologic scores (median±interquartile range) followed a similar pattern (P=0.002). Infarct size did not vary with treatment duration, but neurologic score improved (P=0.002) at all xenon exposure durations (8, 20, and 44 h). Postischemic treatment with either 30% Xe or subtherapeutic hypothermia (36°C) had no effect on 28-day outcome. Combination of these interventions provided long-term benefit. Xenon improved intracerebral hemorrhage outcome measures.Conclusion
Xenon improved focal ischemic outcome at 7, but not 28 days postischemia. Xenon combined with subtherapeutic hypothermia produced sustained recovery benefit. Xenon improved intracerebral hemorrhage outcome. Xenon may have potential for clinical stroke therapy under carefully defined conditions.