Estimating the volume of penumbra in rodents using DTI and stack-based ensemble machine learning framework.

BACKGROUND: This study investigates the potential of diffusion tensor imaging (DTI) in identifying penumbral volume (PV) compared to the standard gadolinium-required perfusion-diffusion mismatch (PDM), utilizing a stack-based ensemble machine learning (ML) approach with enhanced explainability. METHODS: Sixteen male rats were subjected to middle cerebral artery occlusion. The penumbra was identified using PDM at 30 and 90 min after occlusion. We used 11 DTI-derived metrics and 14 distance-based features to train five voxel-wise ML models. The model predictions were integrated using stack-based ensemble techniques. ML-estimated and PDM-defined PVs were compared to evaluate model performance through volume similarity assessment, the Pearson correlation analysis, and Bland-Altman analysis. Feature importance was determined for explainability. RESULTS: In the test rats, the ML-estimated median PV was 106.4 mL (interquartile range 44.6-157.3 mL), whereas the PDM-defined median PV was 102.0 mL (52.1-144.9 mL). These PVs had a volume similarity of 0.88 (0.79-0.96), a Pearson correlation coefficient of 0.93 (p < 0.001), and a Bland-Altman bias of 2.5 mL (2.4% of the mean PDM-defined PV), with 95% limits of agreement ranging from -44.9 to 49.9 mL. Among the features used for PV prediction, the mean diffusivity was the most important feature. CONCLUSIONS: Our study confirmed that PV can be estimated using DTI metrics with a stack-based ensemble ML approach, yielding results comparable to the volume defined by the standard PDM. The model explainability enhanced its clinical relevance. Human studies are warranted to validate our findings. RELEVANCE STATEMENT: The proposed DTI-based ML model can estimate PV without the need for contrast agent administration, offering a valuable option for patients with kidney dysfunction. It also can serve as an alternative if perfusion map interpretation fails in the clinical setting. KEY POINTS: • Penumbral volume can be estimated by DTI combined with stack-based ensemble ML. • Mean diffusivity was the most important feature used for predicting penumbral volume. • The proposed approach can be beneficial for patients with kidney dysfunction.

Effect of Naoluoxintong formula and its split prescriptions on cerebral vascular regeneration in rats with the cerebral ischemia-reperfusion.

OBJECTIVE: To observe regulatory effect of Naoluoxintong formula (, NLXT) and its split prescriptions on vascular regeneration of rats suffering from cerebral ischemia-reperfusion (IR) syndrome of Qi deficiency with blood stasis (QDBS). METHODS: NLXT is the representative prescription of Yiqi Huoxue Tongluo decoction, and NLXT is divided into Yiqi herbs and Huoxue Tongluo herbs according to their efficacies. One hundred and eight specific-pathogen-free, clean-grade, Sprague-Dawley male rats were selected to prepare the classical rat model with QDBS due to middle artery ischemia-reperfusion using the multi-factor compound simulation approach. The animals were classified into sham operation (S), model (M), Nimodping (NMDP), NLXT, YQ and HXTL groups, each having 18 rats. Cerebral ischemia was reperfused after 2 h, and 24 h later, they were administered traditional Chinese medicine treatment for 14 d twice a day. Angiogenesis changes after NLXT administration to middle cerebral artery occlusion-reperfusion (MCAO/R) rats with QDBS were analyzed using the neurological deficit score and hematoxylin-eosin staining. Cerebral infarct area by 2,3,5-Triphenyltetrazolium chloride was detected, and the ultrastructure of the blood vessel in the ischemic frontoparietal cortex was observed by transmission electron microscopy. Angiopoietin 1 (Ang1), angiopoietin 2 (Ang2), vascular endothelial growth factor A (VEGFA), vascular endothelial growth factor receptor 2 (VEGFR2), platelet endothelial cell adhesion molecule-1 (CD31), angiopoietin receptor 2 (Tie2), and P38 mitogen-activated protein kinase (MAPK) protein levels in the frontal and parietal cortex were quantified by immunofluorescence, reverse transcription-polymerase chain reaction, and Western blotting assays. RESULTS: Relative to the S group, VEGFA and VEGFR2 levels in the frontal and parietal cortex of group M were increased, and Ang1, Ang2, Tie2, CD31, and p38 MAPK levels remarkably increased (P < 0.05); cerebral infarct area was significant and pathological morphology and ultrastructure damage was obvious. Relative to the group M, VEGFA, VEGFR2, CD31, Ang1, Ang2, and Tie2 expression of group NLXT and NMDP remarkably elevated (P < 0.05) and infarct focus, pathological morphology and ultrastructure were significantly improved; VEGFA and VEGFR2 levels in the groups YQ and HXTL increased, and Ang1, Ang2, CD31, and Tie2 levels remarkably increased (P < 0.05); p38 MAPK levels in the three treatment groups decreased (P < 0.05). Relative to the group NLXT, the expression levels of p38 MAPK in group YQ and group HXTL were significantly increased, and the expression levels of other indicators were significantly decreased (P < 0.05). CONCLUSION: NLXT can promote the angiogenesis of the rat model of MCAO/R with QDBS by activating VEGFA and inhibiting P38 MAPK, and the effect is better than that of split prescription groups.

Outcomes of decompressive craniectomy for malignant middle cerebral artery stroke in an academic hospital in Brazil / Desfechos da craniectomia descompressiva para infarto maligno da artéria cerebral média em um hospital acadêmico no Brasil

Abstract Background Ischemic stroke is an important cause of death in the world. The malignant middle cerebral artery infarction (MMCAI) has mortality as high as 80% when clinically treated. In this setting, decompressive craniectomy is a life-saving measure, in spite of high morbidity among survivors. Objective To evaluate the outcomes of patients with MMCAI treated with decompressive craniectomy in a Brazilian academic tertiary stroke center. Methods A prospective stroke database was retrospectively evaluated, and all patients treated with decompressive craniectomy for MMCAI between January 2014 and December 2017 were included. The demographics and clinical characteristics were evaluated. The functional outcome, measured by the modified Rankin Scale (mRS), was assessed at hospital discharge, after 3-months and 1-year of follow-up. Results We included 53 patients on the final analysis. The mean age was 54.6 ± 11.6 years and 64.2% were males. The median time from symptoms to admission was 4.8 (3-9.7) hours and the mean time from symptoms to surgery was 36 ± 17 hours. The left hemisphere was the affected in 39.6%. The median NIHSS at admission was 20 (16-24). The in-hospital mortality was 30.2%. After a median of 337 [157-393] days, 47.1% of patients had achieved favorable outcome (mRS ≤ 4) and 39.6% had died. Conclusion Decompressive craniectomy is a life-saving measure in the setting of MMCAI, and its effects remains important in the scenario of a middle-income country in real-world situations.

Resumo Antecedentes O acidente vascular cerebral (AVC) isquêmico é uma causa importante da morte em todo o mundo. O infarto maligno da artéria cerebral média (IMACM) tem mortalidade de até 80% quando tratado clinicamente. Nesse contexto, a craniectomia descompressiva é uma medida salvadora de vidas, apesar da alta morbidade entre os sobreviventes. Objetivo Avaliar os desfechos dos pacientes com IMACM tratados com craniectomia descompressiva em um centro acadêmico terciário de AVC no Brasil. Métodos Um banco de dados prospectivo de AVC foi avaliado retrospectivamente e todos os pacientes tratados com craniectomia descompressiva para IMACM entre janeiro de 2014 e dezembro de 2017 foram incluídos. As características clínicas e demográficas foram avaliadas. Os desfechos funcionais, medidos pela escala modificada da Rankin (mRS), foram avaliados na alta hospitalar, após 3 meses e após 1 ano de seguimento. Resultados Foram incluídos 53 pacientes na análise final. A idade média foi 54,6 ± 11,6 anos e 64,2% eram homens. A mediana do tempo dos sintomas à admissão foi 4,8 (3-9,7) horas e o tempo médio dos sintomas à cirurgia foi 36 ± 17 horas. O hemisfério esquerdo foi o afetado em 39,6%. A pontuação na escala de AVC do National Institute of Health (NIHSS) à admissão foi 20 (16-24). A mortalidade hospitalar foi 30,2%. Após uma mediana de 337 (157-393) dias, 47,1% dos pacientes tinham atingido um desfecho favorável (mRS ≤ 4) e 39,6% tinham morrido. Conclusão Craniectomia descompressiva é uma medida salvadora de vidas no contexto do IMACM e seus efeitos permanecem importantes no cenário de um país em desenvolvimento em situação de vida real.

Time course of hemispheric cerebral volume after decompressive craniectomy in malignant middle cerebral artery stroke / Evolução temporal do volume hemisférico cerebral após craniectomia descompressiva em infarto maligno de artéria cerebral média

Abstract Background Brain edema is the leading cause of death in patients with malignant middle cerebral artery (MCA) infarction. Midline shift (MLS) has been used as a monohemispheric brain edema marker in several studies; however, it does not precisely measure brain edema. It is now possible to directly measure hemisphere brain volume. Knowledge about the time course of brain edema after malignant middle cerebral artery infarction may contribute to the condition's management. Objective Therefore, our goal was to evaluate the course of brain edema in patients with malignant MCA infarction treated with decompressive craniectomy (DC) using hemispheric volumetric measurements. Methods Patients were selected consecutively from a single tertiary hospital between 2013 and 2019. All patients were diagnosed with malignant middle cerebral artery infarction and underwent a decompressive craniectomy (DC) to treat the ischemic event. All computed tomography (CT) exams performed during the clinical care of these patients were analyzed, and the whole ischemic hemisphere volume was calculated for each CT scan. Results We analyzed 43 patients (197 CT exams). Patients' mean age at DC was 51.72 [range: 42-68] years. The mean time between the ischemic ictus and DC was 41.88 (range: 6-77) hours. The mean time between the ischemic event and the peak of hemisphere volume was 168.84 (95% confidence interval [142.08, 195.59]) hours. Conclusion In conclusion, the peak of cerebral edema in malignant MCA infarction after DC occurred on the 7th day (168.84 h) after stroke symptoms onset. Further studies evaluating therapies for brain edema even after DC should be investigated.

Resumo Antecedentes O edema cerebral é a principal causa de morte em pacientes com infarto maligno de artéria cerebral média. O desvio da linha média tem sido utilizado como marcador de edema cerebral mono-hemisférico em alguns estudos; porém, ele não mede de forma precisa o edema cerebral. Atualmente é possível mensurar diretamente o volume do hemisfério cerebral. O conhecimento sobre a evolução temporal do edema cerebral após infartos malignos da artéria cerebral média pode contribuir para o cuidado clínico desta condição. Objetivo Nosso objetivo é avaliar o edema hemisférico ao longo do tempo, em pacientes com infarto maligno da artéria cerebral média, tratados com craniectomia descompressiva. Métodos Os pacientes foram selecionados de forma consecutiva, em um hospital terciário, entre 2013 e 2019. Todos os pacientes apresentavam diagnóstico de infarto maligno de artéria cerebral média e foram submetidos a craniectomia descompressiva. Todas as tomografias computadorizadas de crânio destes pacientes foram analizadas, e o volume do hemisfério cerebral infartado foi mensurado. Resultados Analisamos 43 pacientes (197 tomografias de crânio). A idade média dos pacientes na craniectomia descompressiva foi 51,72 (42-68) anos. O tempo médio entre o ictus e a craniectomia descompressiva foi 41,88 (6-77) horas. O tempo médio entre o ictus e o pico do volume hemisférico foi 168,84 (142,08-195,59) horas. Conclusão O pico do volume cerebral em pacientes com infarto maligno de artéria cerebral média submetidos a craniectomia descompressiva ocorreu no 7o dia (168,84 horas) após o infarto. Mais estudos avaliando terapêuticas direcionadas ao edema cerebral seriam úteis neste contexto.

Efficacy of Baishao Luoshi decoction on synaptic plasticity in rats with post stroke spasticity.

OBJECTIVE: To evaluate the efficacy of Baishao Luoshi decoction (, BD) on synaptic plasticity in rats with post stroke spasticity (PSS), and to study the mechanism behind the action. METHODS: The PSS model of rat was established by middle cerebral artery occlusion (MCAO). The neurological deficit symptoms were evaluated by modified neurological deficit score (mNSS). Muscle tension were evaluated by Modified Ashworth score (MAS). Transmission electron microscopy (TEM) was used to observe the synaptic ultrastructure. The expression of synaptic plasticity-related protein brain derived neurotrophic factor (BDNF), growth associated protein-43 (GAP43), synaptophysin (p38) and microtubule-associated protein 2 (MAP2) in the brain tissue around the infarct were detected by Western blotting. RESULTS: We found that mNSS were significantly improved and limb spasticity was ameliorated treated by BD. The thickness of postsynaptic density and the synaptic curvature increased significantly. The expression of synaptic plasticity-related protein BDNF, GAP43, p38, MAP2 in the brain tissue around the infarct were raised remarkably after treated by BD. CONCLUSIONS: Alleviating PSS by BD may be related to rescuing the synaptic plasticity, which provides a probable new therapeutic method for PSS.

Petrous Carotid Artery Thrombosis in an Immunocompromised Patient Presenting With Mastoiditis, A Case Report.

OBJECTIVES: The neurotologic literature commonly describes venous sinus thrombosis as a complication of mastoiditis. However, thrombosis of the internal carotid artery in the setting of mastoiditis is rarely described. We aim to document a case of carotid artery thrombosis in a patient presenting with mastoiditis. METHODS: We describe this case and review relevant literature. RESULTS: A renal transplant patient was transferred to our hospital with a left middle cerebral artery (MCA) infarct due to acute mastoiditis. Examination demonstrated middle ear effusion and radiologic workup confirmed mastoid infection adjacent to the site of arterial thrombosis. During cortical mastoidectomy and facial recess approach to the middle ear, the petrous carotid bone was found to be dehiscent with pneumatization of the petrous apex. Thrombosis was found to resolve following surgery, IV antibiotics and anticoagulation. Clinically, his focal neurological deficits improved. Proximity of the infectious process to an exposed petrous carotid artery supports the hypothesis that this patient's thrombus was a product of infectious spread and extra-luminal compression. CONCLUSION: To our knowledge, this is the first report of MCA infarction due to petrous ICA arterial thrombus in the setting of mastoid infection. The patient's immunocompromised state may have predisposed and contributed to the adverse outcome. We advocate for aggressive management of acute mastoiditis in the immunocompromised to prevent or manage complications (such as venous thrombophlebitis as well as ICA thrombus) as these patients don't show typical signs of infection and inflammation.

Effcacy-oriented compatibility for Tianma (), Yanlingcao () and Bingpian () on improving cerebral ischemia stroke by network pharmacology and serum pharmacological methods.

OBJECTIVE: To evaluate the compatibility of Tianma (, TM), Yanlingcao (, YLC) and Bingpian (, BP), and their efficacy in the treatment of cerebral ischemic stroke. METHODS: Network pharmacology was used to determine the compatibility of TM, YLC, and BP, and their potential mechanism. The middle cerebral artery occlusion (MCAO) rat model was used to evaluate the curative effect of the six combinations of TM, YLC, and BP (TZB1-TZB6) on cerebral ischemia, by using the weight matching method to form. The potential component changes of TM and YLC in the blood and brains of rats were analyzed using ultra performance liquid chromatography-mass spectrometry. Finally, molecular docking linked the results of animal experiments and network pharmacology, determining the potential component contributors of TM and YLC to treating ischemic stroke. RESULTS: TZB reduced the cerebral infarct volume and protected the nerve cells in MCAO rats. The components of TM and YLC were also identified in the blood and brain homogenate, and BP can facilitate the entry of the components of TM and YLC into the blood and brain. Diosgenin, pennogenin, and gastrodin induced effective binding activities with adenosine receptor a1. CONCLUSION: We investigate an approach that improves the means of folk prescription combined with multi technology that maybe promote the transformation of Chinese medicinal prescription into component-based Chinese medicine.

Different training patterns at recovery stage improve cognitive function in ischemic stroke rats through regulation of the axonal growth inhibitor pathway.

Running wheel exercise training (RWE) and skilled reaching training (SRT) are physical training approaches with positive effects on cognitive function. However, few studies have compared the different effects of these exercises on long-term memory, and their mechanism remains unknown. This study investigated the effects of SRT and RWE, at the recovery stage, on the cognitive function of transient middle cerebral artery occlusion (tMCAO) rats and explored their association with NgR1/Rho-A/ROCK/LOTUS/LGI1 signaling. Adult Sprague-Dawley rats (n = 55) were divided into four groups after pretraining: SRT, RWE, tMCAO, and Sham. Rats were subjected to modified neurological severity score (mNSS) measurements and forelimb grip strength and the Morris water maze tests. Using immunofluorescence and western blotting, we evaluated axonal growth inhibitor expression in the peri-infarct cortex on days 28 and 56 after tMCAO. Results showed the mNSS reduced, whereas the grip strengths improved in RWE and SRT groups. The escape latency in the Morris water maze test was shorter, whereas the number of times of crossing the platform was higher in both the SRT and RWE groups than in the tMCAO group on day 56; furthermore, the parameters in the SRT group improved compared to those in the RWE group. Physical exercise training could improve cognitive functions by reducing the expression of the NgR1/RhoA/ROCK axon growth inhibitors and increasing the expression of the endogenous antagonists LOTUS/LGI1. Exercise training beginning at the recovery stage could improve the cognitive function in tMCAO rats through a mechanism probably associated with the axonal growth inhibitor pathway.

Adenosine A1R/A3R (Adenosine A1 and A3 Receptor) Agonist AST-004 Reduces Brain Infarction in a Nonhuman Primate Model of Stroke.

BACKGROUND AND PURPOSE: Treatment with A1R/A3R (adenosine A1 and A3 receptor) agonists in rodent models of acute ischemic stroke results in significantly reduced lesion volume, indicating activation of adenosine A1R or A3R is cerebroprotective. However, dosing and timing required for cerebroprotection has yet to be established, and whether adenosine A1R/A3R activation will lead to cerebroprotection in a gyrencephalic species has yet to be determined. METHODS: The current study used clinical study intervention timelines in a nonhuman primate model of transient, 4-hour middle cerebral artery occlusion to investigate a potential cerebroprotective effect of the dual adenosine A1R/A3R agonist AST-004. Bolus and then 22 hours intravenous infusion of AST-004 was initiated 2 hours after transient middle cerebral artery occlusion. Primary outcome measures included lesion volume, lesion growth kinetics, penumbra volume as well as initial pharmacokinetic-pharmacodynamic relationships measured up to 5 days after transient middle cerebral artery occlusion. Secondary outcome measures included physiological parameters and neurological function. RESULTS: Administration of AST-004 resulted in rapid and statistically significant decreases in lesion growth rate and total lesion volume. In addition, penumbra volume decline over time was significantly less under AST-004 treatment compared with vehicle treatment. These changes correlated with unbound AST-004 concentrations in the plasma and cerebrospinal fluid as well as estimated brain A1R and A3R occupancy. No relevant changes in physiological parameters were observed during AST-004 treatment. CONCLUSIONS: These findings suggest that administration of AST-004 and combined A1R/A3R agonism in the brain are efficacious pharmacological interventions in acute ischemic stroke and warrant further clinical evaluation.

Effects of electroacupuncture pretreatment on motor function and cerebral blood flow in MCAO model rats / 针灸推拿医学（英文版）

Objective: To observe the effects of electroacupuncture (EA) pretreatment on motor function, cerebral blood flow, cerebral infarction volume, and vascular endothelial growth factor (VEGF) level in middle cerebral artery occlusion (MCAO) model rats. Methods: Twenty-four male Sprague-Dawley rats were randomly divided into a normal group, a model group, and an EA group, with eight rats in each group. The middle cerebral artery ischemia-reperfusion model was established by the suture-occluded method in the model group and the EA group, while not in the normal group. The EA group was pretreated with EA at bilateral Fengchi (GB20) before model preparation, once a day for 30 min each time for a total of 7 d. The changes in the CatWalk gait parameters, modified Bederson neurological deficit score, cerebral blood flow, cerebral infarction volume after ischemia, and VEGF level in the brain tissue of rats in each group were observed. Results: Compared with the normal group, the modified Bederson neurological deficit score in the model group and the EA group increased after modeling (P<0.05), and the CatWalk gait parameters (one-leg stance duration, gait cadence, and gait cycle) were all changed (P<0.05). Compared with the model group, the modified Bederson neurological deficit score in the EA group decreased (P<0.05), and the CatWalk gait parameters improved (P<0.05). Immediately after ischemia, the cerebral blood flow in the normal group was greater than that in the model group and the EA group (P<0.05); after reperfusion, the cerebral blood flow in the EA group was greater than that in the model group (P<0.05). Compared with the normal group, the cerebral infarction volume in the model group and the EA group increased (P<0.05). Compared with the model group, the cerebral infarction volume in the EA group decreased (P<0.05). The expression level of VEGF-positive cells in the rat brain tissue in the model group was higher than that in the normal group (P<0.05), and was higher in the EA group than in the model group (P<0.05). Conclusion: EA pretreatment improves the limb motor function in MCAO model rats, alleviates the symptoms of neurological deficits, promotes the recovery of cerebral blood flow, reduces the cerebral infarction area after MCAO modeling, and increases the VEGF expression in the brain tissue.

Ischemic stroke in a young patient with human immunodeficiency virus infection due to middle cerebral artery dissection: a case report / 中华神经科杂志

Middle cerebral artery dissection is an uncommon cause of ischemic stroke in young adults, which is extremely rare in the case that it occurs in HIV-infected patients. This article reported a 26-year-old acute cerebral infarction patient with HIV antigen/antibody-positive who started with capsular warning syndrome and progressed to right basal ganglia cerebral infarction. The high-resolution vessel wall imaging showed the characteristic findings of middle cerebral artery dissection including "double luminal" and "intimal flap" signs. The coexistence of HIV-associated vasculopathy and hypertension with high blood pressure variability contributed to the occurrence of middle cerebral artery dissection in the patient. Combined with literature reports, this paper will further explore the relationship between HIV infection and cerebrovascular disease and the possible mechanism of middle cerebral artery dissection.

Prehospital predictors of large-vessel occlusion in acute ischemic stroke / 中国基层医药

Objective:To analyze the prehospital predictors of large-vessel occlusion (LVO) in acute ischemic stroke.Methods:This study recruited patients who had developed LVO for less than 24 hours and had a National Institute of Health Stroke Scale (NIHSS) score ≥ 8 and who received treatment in Lu'an People's Hospital from December 2018 to November 2020. The included patients were divided into LVO and LVO-free groups according to the presence of a large-vessel occlusion determined by magnetic resonance angiography, CT angiography, and digital subtraction angiography. Baseline data (sex, age, disease history, life history, and medication history), NIHSS subscale score, and blood pressure at admission were compared between LVO and LVO-free groups. The efficacy of the factors that were screened for predicting LVO in acute ischemic stroke were compared with the that of commonly used scales.Results:A total of 761 patients with acute ischemic stroke who had an NIHSS score ≥ 8 were included in the final analysis. Among them, 228 patients had an LVO and 533 patients had no LVO. There were significant differences in the proportions of patients with atrial fibrillation ( OR = 5.230, 95% CI = 3.400-8.043, P < 0.001) and systolic blood pressure ≤ 170 mmHg ( OR = 5.181, 95% CI = 3.327-8.068, P < 0.001) between the two groups. Conclusion:Atrial fibrillation and systolic blood pressure ≤ 170 mmHg are greatly associated with the presence of large-vessel occlusion in acute ischemic stroke.

Characterizing Diaschisis-Related Thalamic Perfusion and Diffusion After Middle Cerebral Artery Infarction.

Background and Purpose: Ipsilateral thalamic diaschisis (ITD) initially describes functional depression of the thalamus ipsilateral to a supratentorial lesion, but accumulating evidence has shown morphological changes also occur. Therefore, we aimed to characterize thalamic perfusion and diffusion related to ITD over time and their inter-relationships after middle cerebral artery infarction. Methods: Eighty-five patients with middle cerebral artery infarction who underwent diffusion kurtosis imaging and arterial spin labeling were retrospectively included. ITD was diagnosed as ipsilateral thalamic hypoperfusion present on ≥2 cerebral blood flow maps. The thalamic asymmetrical index was calculated as (ipsilateral value−contralateral value)/contralateral value×100%. Finally, the inter-relationships of thalamic perfusion and diffusion were analyzed. Results: ITD was present in 56/85 patients (65.9%, ITD+). In ITD+ patients, larger abnormal perfusion volume, higher perfusion-infarct mismatch and lower rates of focal hyperperfusion were observed than ITD− patients. Infarction affecting the corona radiata were more frequent among ITD+ patients. Mean kurtosis were slightly but significantly increased within the ipsilateral thalamus compared with the contralateral one in ITD+ patients of subacute and chronic groups, while fractional anisotropy was significantly increased in subacute group but decreased in chronic group for both ITD+ and ITD− patients. Mean diffusivity was significantly increased in ITD+ patients of chronic group. Furthermore, the AICBF was negatively and significantly correlated with AIMK and AIFA in ITD+ patients in subacute group, and AIMD, even after adjustment for abnormal perfusion volume and days from symptoms onset, in chronic group. ITD+ patients had significantly higher National Institutes of Health Stroke Scale and modified Rankin Scale scores at admission and discharge and also showed a trend to independent association with clinical outcome at discharge. Conclusions: The combination of arterial spin labeling and diffusion kurtosis imaging can reveal early, time-specific thalamic perfusion and diffusion changes after middle cerebral artery infarction. ITD-related hypoperfusion was significantly correlated with underlying microstructural alterations.

Enhanced Mesenchymal Stromal Cells or Erythropoietin Provide Long-Term Functional Benefit After Neonatal Stroke.

BACKGROUND AND PURPOSE: Perinatal stroke is a common cause of life-long neurobehavioral compromise. Mesenchymal stromal cells (MSCs) and EPO (erythropoietin) have each demonstrated short-term benefit with delayed administration after stroke, and combination therapy may provide the most benefit. The purpose of this study is to determine the long-term histological and functional efficacy of enhanced, intranasal stem cell therapy (MSC preexposed to EPO) compared with standard MSC or multidose systemic EPO. METHODS: Transient middle cerebral artery occlusion or sham surgery was performed in postnatal day (P) 10 Sprague-Dawley rats, who were treated with single-dose intranasal MSC, MSC preexposed to EPO (MSC/EPO), multidose systemic EPO (EPO3; 1000 u/kg per dose×3 every 72 hours), or cell-conditioned media on P13 (day 3 [P13-P19] for EPO), or on P17 (day 7 [P17-P23] for EPO). At 2 months of age, animals underwent novel object recognition, cylinder rearing, and open field testing to assess recognition memory, sensorimotor function, and anxiety in adulthood. RESULTS: MSC, MSC/EPO, and EPO3 improved brain volume when administered at 3 or 7 days after middle cerebral artery occlusion. MSC/EPO also enhanced long-term recognition memory with either day 3 or day 7 treatment, but EPO3 had the most long-term benefit, improving recognition memory and exploratory behavior and reducing anxiety. CONCLUSIONS: These data suggest that single-dose MSC/EPO and multidose systemic EPO improve long-term neurobehavioral outcomes even when administration is delayed, although EPO was the most effective treatment overall. It is possible that EPO represents a final common pathway for improved long-term repair, although the specific mechanisms remain to be determined.

Correlation of fluid-attenuation inversion recovery vascular hyperintensity and clinical outcome in patients with middle cerebral artery M1 occlusive stroke / 国际脑血管病杂志

Objective:To investigate the correlation of fluid-attenuation inversion recovery (FLAIR) vascular hyperintensity (FVH) and clinical outcome in patients with middle cerebral artery M1 occlusive stroke.Methods:Patients with acute middle cerebral artery M1 occlusive stroke admitted to the Department of Neurology, the Second Affiliated Hospital of Anhui Medical University from June 2018 to September 2019 were enrolled retrospectively. The demographic and clinical data were collected. Diffusion-weighted imaging (DWI)-Alberta Stroke Program Early CT Score (ASPECTS) and FVH score were performed with MRI images. The modified Rankin Scale (MRS) was used to evaluate the clinical outcome at 90 d after onset. 0-2 was defined as good outcome, and >2 was defined as poor outcome. Multivariate logistic regression analysis was used to determine the independent correlation between FVH and the outcome. Results:A total of 65 patients with acute middle cerebral artery M1 occlusive stroke were enrolled, including 37 males (56.9%). Their age was 64.35±12.13 years. Twenty-nine patients (44.6%) had a good outcome, and 36 (55.4%) had a poor outcome. There were significant differences in triglyceride ( P=0.037), antihypertensive drug treatment ( P=0.037), baseline National Institutes of Health Stroke Scale (NIHSS) score ( P<0.001), DWI-ASPECTS ( P=0.017) and FVH score ( P<0.001) between the poor outcome group and the good outcome group. Multivariate logistic regression analysis showed that FVH score (odds ratio 6.477, 95% confidence interval 1.570-26.716; P=0.010) and NIHSS score (odds ratio 1.869, 95% confidence interval 1.326-2.635; P<0.001) were significantly independently correlated with the poor outcome. However, there was no significant independent correlation between DWI-ASPECTS and the outcome (odds ratio 0.451, 95% confidence interval 0.068-2.988; P=0.410). Conclusions:FVH score is an independent risk factor for poor outcome in patients with acute middle cerebral artery M1 occlusive stroke.

Risk factors and early neurological deterioration in proximal single subcortical infarction: comparison with distal single subcortical infarction / 国际脑血管病杂志

Objective:To investigate the risk factors for different types of single subcortical infarction (SSI) in middle cerebral artery territory and the risk factors for early neurologic deterioration (END).Methods:Patients with SSI in middle cerebral artery territory admitted to the Department of Neurology, People's Hospital Affiliated to Jiangsu University from January 2020 to April 2021 were enrolled retrospectively. According to the distribution of infarction, the patients were divided into proximal SSI (pSSI) and distal SSI (dSSI). The demographics, vascular risk factors and baseline clinical data were collected. END was defined as new signs and/or symptoms of neurological deficit or aggravation of any neurological deficit within 2 weeks after onset. Multivariate logistic regression analysis was used to determine the independent risk factors for pSSI and END. Results:Seventy-six patients with acute SSI in the middle cerebral artery territory were included, 41 patients (53.9%) in the pSSI group, 35 (46.1%) in the dSSI group; 13 (17.1%) in the END group, and 63 (82.9%) in the non-END group. There were no significant differences in age, gender, vascular risk factors and baseline National Institutes of Health Stroke Scale score between the pSSI group and the dSSI group. The total cholesterol, fasting blood glucose levels and the ratio of pSSI in the END group were significantly higher than those in the non-END group ( P<0.05), while the high-density lipoprotein cholesterol level was significantly lower than that of the non-END group ( P<0.05). Multivariate logistic regression analysis showed that pSSI was an independent risk factor for the occurrence of END in patients with SSI (odds ratio 6.75, 95% confidence interval 1.26-36.23; P=0.026). Conclusion:There was no significant difference in risk factors between pSSI and dSSI, but patients with pSSI were more prone to END.

Sustained Increases in Immune Transcripts and Immune Cell Trafficking During the Recovery of Experimental Brain Ischemia.

BACKGROUND AND PURPOSE: Stroke is a major cause of chronic neurological disability. There is considerable interest in understanding how acute transcriptome changes evolve into subacute and chronic patterns that facilitate or limit spontaneous recovery. Here we mapped longitudinal changes in gene expression at multiple time points after stroke in mice out to 6 months. METHODS: Adult C57BL/6 mice were subjected to transient middle cerebral artery occlusion. Longitudinal transcriptome levels were measured at 10 time points after stroke from acute to recovery phases of ischemic stroke. Localization and the number of mononuclear phagocytes were determined in the postischemic brain. Whole-mount brain imaging was performed in asplenic mice receiving GFP+ (green fluorescent protein)-tagged splenocytes. RESULTS: Sustained stroke-induced mRNA abundance changes were observed in both hemispheres with 2989 ipsilateral and 822 contralateral genes significantly perturbed. In the hemisphere ipsilateral to the infarct, genes associated with immune functions were strongly affected, including temporally overlapping innate and adaptive immunity and macrophage M1 and M2 phenotype-related genes. The strong immune gene activation was accompanied by the sustained infiltration of peripheral immune cells at acute, subacute, and recovery stages of stroke. The infiltrated immune cells were found in the infarcted area but also in remote regions at 2 months after stroke. CONCLUSIONS: The study identifies that immune components are the predominant molecular signatures and they may propagate or continuously respond to brain injury in the subacute to chronic phase after central nervous system injury. The study suggests a potential immune-based strategy to modify injury progression and tissue remodeling in ischemic stroke, even months after the initiating event.

Effect of Danhong injection combined with edaravone in the treatment of patients with acute cerebral infarction and its influence on cytokines,cerebral hemodynamics and vascular endothelial function / 中国基层医药

Objective To investigate the effect of Danhong injection combined with edaravone in the treatment of patients with acute cerebral infarction,and its influence on cytokines,cerebral hemodynamics and vascular endothelial function.Methods From March 2018 to March 2019,142 patients with acute cerebral infarction treated in the People's Hospital of Yuhuan were randomly divided into treatment group and control group according to the digital table,with 71 cases in each group.The treatment group was treated with Danhong injection combined with edaravone,while the control group was only treated with edaravone.Both two groups were treated for 2 weeks.The therapeutic effects,changes of cytokines,cerebral hemodynamics,vascular endothelial function,activity of daily living index(Barthel index) and neurological deficit score(NIHSS score) before and after treatment were compared between the two groups.Results The total effective rate of the treatment group was 90.14％ (64/71),which was higher than 74.65％ (53/71) of the control group,the difference was statistically significant(x2 =5.874,P ＜ 0.05).After treatment,the serum levels of CRP [(5.43 ± 1.20) mg/L] and IL-6 [(32.15 ± 7.39) ng/L] in the treatment group were lower than those in the control group [(9.38 ± 1.74) mg/L and (67.43 ± 10.29) ng/L] (t =15.747,23.465,all P ＜0.05).After treatment,the Vp [(69.83 ± 3.24) v ·-1 · s-1] and Vm [(35.24 ± 2.10) v ·-1 · s-1] in the treatment group were higher than those in the control group [(63.81 ± 2.68) v ·-1 · s-1 and (32.18 ± 1.73) v ·-1s-1],while the PI in the treatment group [(0.72 ± 0.04)] was lower than that in the control group [(0.83 ±0.07)],the differences were statistically significant (t =12.064,9.477,11.497,all P ＜ 0.05).After treatment,the serum level of ET-1 [(60.17 ± 5.46) mg/L] in the treatment group was lower than that in the control group[(73.21 ±6.78)mg/L],while the NO level in the treatment group[(72.15 ±7.39) ng/L] was higher than that in the control group [(61.43 ± 10.29) ng/L],the differences were statistically significant (t =12.622,7.130,all P ＜0.05).After treatment,the Barthel index score of the treatment group [(68.93 ± 7.83) points] was higher than that of the control group [(54.57 ± 7.38)points],while the NIHSS score of the treatment group [(9.34 ± 1.97)points] was lower than that of the control group [(14.54 ± 2.89) points],the differences were statistically significant (t =11.246,12.528,all P ＜ 0.05).Conclusion Danhong injection combined with edaravone in the treatment of acute cerebral infarction is effective,which can alleviate inflammation and improve cerebral hemodynamics and vascular endothelial dysfunction.