Protective Effects of Butylphthalide on Cerebral Infarction Induced by Local Ischemic Injury and Regulation Mechanism of the Pi3k/Akt/Gsk-3β Signaling Pathway

Aim: We aimed to study the protective effects of butylphthalide (NBP) on cerebral infarction induced by local ischemic injury and regulation mechanism of the PI3K/Akt/GSK-3β signaling pathway. Materials and methods: One hundred male Wistar rats aged 12-15 weeks were randomly divided into 5 groups (n=20). The middle cerebral artery occlusion (MCAO) model was established. NBP, P13K specific inhibitor LY294002 and NBP plus LY294002 groups were intraperitoneally administered on the first day after modeling, once a day for 7 days. Sham operation (Sham) and model groups were intraperitoneally given equal amounts of normal saline. Modified neurological severity (mNS) was scored 30 min after administration on the 7th day, and cerebral infarction volume was measured by magnetic resonance imaging. Neuronal damage was detected by Nissl staining. Intact neurons were counted under light microscope. The protein expressions of Akt, P-Akt, GSK-3β and P-GSK-3β were detected by Western blotting. Results:The mNS score of NBP group decreased significantly compared with that of model group (P<0.05). Compared with model group, the cerebral infarction volume of NBP group significantly reduced (P<0.05). Compared with model group, the number of intact neurons in NBP group significantly increased (P<0.05). Compared with model group, the phosphorylation levels of Akt and GSK-3β in NBP group significantly increased (P<0.05). Conclusions: By activating the PI3K/Akt/GSK-3β signaling pathway, NBP relieves neurological function damage and protects against cerebral infarction induced by local ischemic injury.

Stroke Patients With Faster Core Growth Have Greater Benefit From Endovascular Therapy

Background and Purpose: This study aimed to explore whether the therapeutic benefit of endovascular thrombectomy (EVT) was mediated by core growth rate. Methods: This retrospective cohort study identified acute ischemic stroke patients with large vessel occlusion and receiving reperfusion treatment, either EVT or intravenous thrombolysis (IVT), within 4.5 hours of stroke onset. Patients were divided into 2 groups: EVT versus IVT only patients (who had no access to EVT). Core growth rate was estimated by the acute core volume on perfusion computed tomography divided by the time from stroke onset to perfusion computed tomography. The primary clinical outcome was good outcome defined by 3-month modified Rankin Scale score of 0–2. Tissue outcome was the final infarction volume. Results: A total of 806 patients were included, 429 in the EVT group (recanalization rate of 61.6%) and 377 in the IVT only group (recanalization rate of 44.7%). The treatment effect of EVT versus IVT only was mediated by core growth rate, showing a significant interaction between EVT treatment and core growth rate in predicting good clinical outcome (interaction odds ratio=1.03 [1.01–1.05], P =0.007) and final infarct volume (interaction odds ratio=−0.44 [−0.87 to −0.01], P =0.047). For patients with fast core growth of >25 mL/h, EVT treatment (compared with IVT only) increased the odds of good clinical outcome (adjusted odds ratio=3.62 [1.21–10.76], P =0.021) and resulted in smaller final infarction volume (37.5 versus 73.9 mL, P =0.012). For patients with slow core growth of <15 mL/h, there were no significant differences between the EVT and the IVT only group in either good clinical outcome (adjusted odds ratio=1.44 [0.97–2.14], P =0.070) or final infarction volume (22.6 versus 21.9 mL, P =0.551). Conclusions: Fast core growth was associated with greater benefit from EVT compared with IVT in the early <4.5-hour time window.

Network pharmacology and molecular docking reveal the effective substances and active mechanisms of Dalbergia Odoriferain protecting against ischemic stroke

Dalbergia Odorifera (DO) has been widely used for the treatment of cardiovascular and cerebrovascular diseasesinclinical. However, the effective substances and possible mechanisms of DO are still unclear. In this study, network pharmacology and molecular docking were used toelucidate the effective substances and active mechanisms of DO in treating ischemic stroke (IS). 544 DO-related targets from 29 bioactive components and 344 IS-related targets were collected, among them, 71 overlapping common targets were got. Enrichment analysis showed that 12 components were the possible bioactive components in DO, which regulating 9 important signaling pathways in 3 biological processes including ‘oxidative stress’ (KEGG:04151, KEGG:04068, KEGG:04915), ‘inflammatory response’(KEGG:04668, KEGG:04064) and ‘vascular endothelial function regulation’(KEGG:04066, KEGG:04370). Among these, 5 bioactive components with degree≥20 among the 12 potential bioactive components were selected to be docked with the top5 core targets using AutodockVina software. According to the results of molecular docking, the binding sites of core target protein AKT1 and MOL002974, MOL002975, and MOL002914 were 9, 8, and 6, respectively, and they contained 2, 1, and 0 threonine residues, respectively. And some binding sites were consistent, which may be the reason for the similarities and differences between the docking results of the 3 core bioactive components. The results of in vitro experiments showed that OGD/R could inhibit cell survival and AKT phosphorylation which were reversed by the 3 core bioactive components. Among them, MOL002974 (butein) had a slightly better effect. Therefore, the protective effect of MOL002974 (butein) against cerebral ischemia was further evaluated in a rat model of middle cerebral artery occlusion (MCAO) by detecting neurological score, cerebral infarction volume and lactate dehydrogenase (LDH) level. The results indicated that MOL002974 (butein) could significantly improve the neurological score of rats, decrease cerebral infarction volume, and inhibit the level of LDH in the cerebral tissue and serum in a dose-dependent manner. In conclusion, network pharmacology and molecular docking predicate the possible effective substances and mechanisms of DO in treating IS. And the results are verified by the in vitro and in vivo experiments. This research reveals the possible effective substances from DO and its active mechanisms for treating IS and provides a new direction for the secondary development of DO for treating IS.

Brain infarctions after glioma surgery: prevalence, radiological characteristics and risk factors

Background Prevalence, radiological characteristics, and risk factors for peritumoral infarctions after glioma surgery are not much studied. In this study, we assessed shape, volume, and prevalence of peritumoral infarctions and investigated possible associated factors. Methods In a prospective single-center cohort study, we included all adult patients operated for diffuse gliomas from January 2007 to December 2018. Postoperative infarctions were segmented using early postoperative MRI images, and volume, shape, and location of postoperative infarctions were assessed. Heatmaps of the distribution of tumors and infarctions were created. Results MRIs from 238 (44%) of 539 operations showed restricted diffusion in relation to the operation cavity, interpreted as postoperative infarctions. Of these, 86 (36%) were rim-shaped, 103 (43%) were sector-shaped, 40 (17%) were a combination of rim- and sector-shaped, and six (3%) were remote infarctions. Median infarction volume was 1.7 cm3 (IQR 0.7–4.3, range 0.1–67.1). Infarctions were more common if the tumor was in the temporal lobe, and the map shows more infarctions in the periventricular watershed areas. Sector-shaped infarctions were more often seen in patients with known cerebrovascular disease (47.6% vs. 25.5%, p = 0.024). There was a positive correlation between infarction volume and tumor volume (r = 0.267, p < 0.001) and infarction volume and perioperative bleeding (r = 0.176, p = 0.014). Moreover, there was a significant positive association between age and larger infarction volumes (r = 0.193, p = 0.003). Infarction rates and infarction volumes varied across individual surgeons, p = 0.037 (range 32–72%) and p = 0.026. Conclusions In the present study, peritumoral infarctions occurred in 44% after diffuse glioma operations. Infarctions were more common in patients operated for tumors in the temporal lobe but were not more common following recurrent surgeries. Sector-shaped infarctions were more common in patients with known cerebrovascular disease. Increasing age, larger tumors, and more perioperative bleeding were factors associated with infarction volumes. The risk of infarctions and infarction volumes may also be surgeon-dependent.

Delta Sleep-Inducing Peptide Recovers Motor Function in SD Rats after Focal Stroke

Background and Objectives: Mutual effect of the preliminary and therapeutic intranasal treatment of SD rats with DSIP (8 days) on the outcome of focal stroke, induced with intraluminal middle cerebral occlusion (MCAO), was investigated. Materials and Methods: The groups were the following: MCAO + vehicle, MCAO + DSIP, and SHAM-operated. DSIP or vehicle was applied nasally 60 (±15) minutes prior to the occlusion and for 7 days after reperfusion at dose 120 µg/kg. The battery of behavioral tests was performed on 1, 3, 7, 14, and 21 days after MCAO. Motor coordination and balance and bilateral asymmetry were tested. At the end of the study, animals were euthanized, and their brains were perfused, serial cryoslices were made, and infarction volume in them was calculated. Results: Although brain infarction in DSIP-treated animals was smaller than in vehicle-treated animals, the difference was not significant. However, motor performance in the rotarod test significantly recovered in DSIP-treated animals. Conclusions: Intranasal administration of DSIP in the course of 8 days leads to accelerated recovery of motor functions.

Genome-Wide Transcription Analysis of Electroacupuncture Precondition-Induced Ischemic Tolerance on SD Rat With Ischemia–Reperfusion Injury

Acupuncture promotes the recovery of neurological function by the overall improvement of ischemic brain injury. It is not only regarded as a rehabilitative treatment but also a pretreatment method for stroke. However, its mechanism has not been fully elucidated. In this study, rats were treated with electroacupuncture (EA) at Baihui (GV20) for 30 min/day for 6 days, ahead of conducting cerebral ischemia–reperfusion (I/R) injury. Infarction volume, Evans blue leakage, and neurological deficits were evaluated at 24 h after I/R injury. Then, the ipsilateral ischemic brain was isolated for RNA sequencing (RNA-Seq) to identify molecular consequences. The results showed that EA pretreatment decreased blood–brain barrier (BBB) permeability, reduced brain infarction volume, and improved neurological outcomes. EA pretreatment could upregulate expression of antivirus and immunity activity-associated genes (such as Ifit1, Ifit3, Irf7, and Oasla) and downregulate expression of matrix disruption-associated genes (Col24a1, Col11a1, Col27a1, etc.) in healthy rats. In addition, it could partially reverse or ameliorate genome-wide transcription changes of the ipsilateral ischemic brain. For the first time, this study provides insight into genomic network modulation of a healthy rat with EA treatment and a EA-preconditioned rat under subsequent I/R injury, which is helpful in explaining acupuncture precondition-induced ischemic tolerance of stroke. It also provides new strategies and targets for the prevention of ischemic stroke.

Choroidal artery ischemic events after temporal lobe epilepsy surgery: clinical outcome, quality of life, and surgical pitfalls

OBJECTIVE Ischemic events within the territory of the choroidal artery are an important cause of morbidity after temporal lobe epilepsy (TLE) surgery. The aim of the present study was to evaluate the rate of these ischemic events, their clinical presentation, and impact on patients’ health-related quality of life (HRQoL) after TLE surgery. METHODS Four hundred twenty-two consecutive patients undergoing temporal resections for drug-resistant TLE were retrospectively analyzed. All patients underwent presurgical multidisciplinary assessment using a standard protocol comprising clinical, neuroradiological, neuropsychological, and EEG data. Postoperative complications with corresponding imaging, neurological deficits, and disease-specific HRQoL questionnaires were evaluated. RESULTS The overall complication rate was 7.8% (n = 33). Fourteen patients (3.3%) suffered from ischemic events causing 6 permanent motor deficits, 3 with permanent aphasias, and 6 visual field defects that exceeded quadrantanopia. In 8 patients with anterior choroidal artery infarction, accounting for 57% of all ischemic events, infarction volume correlated positively with the occurrence of new permanent neurological deficits (8666 vs 1692 mm3, p = 0.032). Despite the occurrence of ischemic events, HRQoL improved in 71% of patients. However, infarction volume showed a negative correlation trend with HRQoL (Pearson’s r = −0.390, p = 0.094). There was a trend toward increased risk for ischemic events in patients who underwent selective amygdalohippocampectomy compared to patients who underwent anterior temporal lobectomy or temporal lesionectomy (RR 0.96, 95% CI 0.93–0.99, p = 0.08). CONCLUSIONS Choroidal artery infarctions are rare but relevant complications after TLE surgery, presenting with variable clinical courses ranging from devastating neurological deterioration to complete recovery. Despite the occurrence of postoperative infarction, most patients report improvement of HRQoL after TLE surgery. This study showed that the type of surgery appears to modulate the risk for these ischemic events.

Electroacupuncture in the Contralesional Hemisphere Improves Neurological Function Involving GABA in Ischemia–Reperfusion Injury Rats

This study investigated the effect and mechanism of electroacupuncture (EA) on the contralesional hemisphere in rats with ischemic stroke. EA of 2 Hz was applied on the contralesionally Luoque (BL8) and Tongtian (BL7) acupoints of the scalp to investigate the neurological status and mechanism in ischemia–reperfusion injury rats. The differences in the neurological deficit score and Rotarod test time between days 3 and 15 after reperfusion were significantly lower in the sham group (0.00 (−1.00, 0.00) and 3.53 (−0.39, 7.48) second, respectively) than in the EA group (−4.00 (−4.00, −3.00) and 44.80 (41.69, 54.13) second, respectively, both p < 0.001 ). The ratio of infarction volume was 0.19 ± 0.04 in the sham group greater than 0.07 ± 0.04 in the EA group ( p < 0.001 ). On day 15, in the cerebral cortex of the lesioned hemisphere, the gamma-aminobutyric acid (GABA)-A/actin ratio in the normal group (1.11 ± 0.36) was higher than that in the sham group (0.38 ± 0.07, p < 0.05 ) and similar to that in the EA group (0.69 ± 0.18, p > 0.05 ); the difference between the EA and sham groups was significant ( p < 0.05 ). EA of 2 Hz on the BL8 and BL7 acupoints on the contralesional scalp can improve motor function and also can reduce infarction volume, and this effect of EA, and that GABA-A, plays at least a partial role in ischemia–reperfusion injury rats.

Omentin-1: a biomarker in large artery ischaemic stroke patients

Background Omentin-1 is a novel adipocytokine that is related to atherosclerosis-based ischaemic cardiovascular disease and stroke. Previous studies have linked its lower levels with poor stroke outcomes. We aimed to assess the level of serum omentin-1 as a prognostic marker in patients with large artery ischaemic stroke. Methods Fifty ischaemic stroke patients suffering large artery ischaemic stroke and another 50 subjects without a prior history of strokes were recruited. All participants were subjected to neurological examinations, echocardiography and laboratory investigations including a lipid profile and HBA1c. Carotid intima-media thickness (IMT) was measured for all participants. Stroke patients were evaluated by the National Institute of Health Stroke Scale (NIHSS) and the modified Rankin Scale (mRS). Infarction volume was measured by magnetic resonance image (MRI) and serum level of omentin-1 was gauged for all participants. Results Carotid IMT significantly increased in stroke patients compared to control subjects. While serum omentin-1 levels were higher in control non-diabetic subjects, they were lower in diabetic patients with ischaemic stroke. Serum omentin-1 levels were inversely correlated with NIHSS, carotid IMT, infarction volume and mRS scores in all stroke patients. Serum omentin-1 level less than 24.5 ng/ml showed 93.7%sensitivity and 44.4% specificity in prediction of poor stroke outcome while values less than 27.8 ng/ml in non-diabetic stroke patients had sensitivity and specificity with 87.5% and 55.6% respectively. Conclusion Lower levels of serum omentin-1 are associated with increased ischaemic stroke severity and poor functional outcome.