Short-term Neurological Function Research Articles

Elevated neutrophil-to-lymphocyte ratio

Objective: This study aimed to determine the risk factors associated with short-term neurological decline in acute ischemic stroke patients with large vessel occlusion (LVO) who have undergone successful endovascular recanalization through mechanical thrombectomy. Subjects and Methods: We included 168 LVO patients who had successful recanalization in this study. We collected the patients' demographic data and related disease test results. We noted the National Institutes of Health Stroke Scale (NIHSS) scores at the onset and on the 7th day postonset. After comparing the NIHSS scores at these two time points, we analyzed the correlation between the collected data and the NIHSS scores. We selected the logistic regression model variables based on the correlation significance. We included gender, age, diastolic blood pressure, glycosylated hemoglobin, urea nitrogen, hemoglobin, neutrophil-to-lymphocyte ratio (NLR), low-density lipoprotein, and total protein in a logistic regression model. We used the receiver operating characteristic (ROC) curve to evaluate the predictive power of NLR for deterioration. Results: Mechanical thrombectomy significantly lowered the median NIHSS score of LVO patients on the 7th day of onset, while a subset of patients experienced an increased NIHSS score. Correlation analysis revealed significant correlations between the NIHSS score at onset and diastolic pressure, white blood cell count, neutrophil count, creatinine, and urea nitrogen. On the 7th day postonset, NIHSS scores showed significant correlations with glycosylated hemoglobin, white blood cell count, neutrophil count, NLR, red blood cell count, hemoglobin, and urea nitrogen. Logistic regression analysis further revealed that patients with higher NLR are at significantly increased risk of short-term neurological decline. ROC analysis indicated that a higher NLR can serve as a diagnostic marker for potential adverse outcomes of mechanical thrombectomy. Conclusion: While mechanical thrombectomy substantially improves neurological deficits in LVO patients, some patients still experience deterioration. Higher NLR at stroke onset is associated with short-term neurological function decline in acute LVO patients postsuccessful recanalization.

Development of a composite diffusion tensor imaging score correlating with short-term neurological status in neonatal hypoxic-ischemic encephalopathy.

Hypoxic–ischemic encephalopathy (HIE) is the most common cause of neonatal acquired brain injury. Although conventional MRI may predict neurodevelopmental outcomes, accurate prognostication remains difficult. As diffusion tensor imaging (DTI) may provide an additional diagnostic and prognostic value over conventional MRI, we aimed to develop a composite DTI (cDTI) score to relate to short-term neurological function. Sixty prospective neonates treated with therapeutic hypothermia (TH) for HIE were evaluated with DTI, with a voxel size of 1 × 1 × 2 mm. Fractional anisotropy (FA) and mean diffusivity (MD) from 100 neuroanatomical regions (FA/MD *100 = 200 DTI parameters in total) were quantified using an atlas-based image parcellation technique. A least absolute shrinkage and selection operator (LASSO) regression was applied to the DTI parameters to generate the cDTI score. Time to full oral nutrition [short-term oral feeding (STO) score] was used as a measure of short-term neurological function and was correlated with extracted DTI features. Seventeen DTI parameters were selected with LASSO and built into the final unbiased regression model. The selected factors included FA or MD values of the limbic structures, the corticospinal tract, and the frontotemporal cortices. While the cDTI score strongly correlated with the STO score (rho = 0.83, p = 2.8 × 10−16), it only weakly correlated with the Sarnat score (rho = 0.27, p = 0.035) and moderately with the NICHD-NRN neuroimaging score (rho = 0.43, p = 6.6 × 10−04). In contrast to the cDTI score, the NICHD-NRN score only moderately correlated with the STO score (rho = 0.37, p = 0.0037). Using a mixed-model analysis, interleukin-10 at admission to the NICU (p = 1.5 × 10−13) and tau protein at the end of TH/rewarming (p = 0.036) and after rewarming (p = 0.0015) were significantly associated with higher cDTI scores, suggesting that high cDTI scores were related to the intensity of the early inflammatory response and the severity of neuronal impairment after TH. In conclusion, a data-driven unbiased approach was applied to identify anatomical structures associated with some aspects of neurological function of HIE neonates after cooling and to build a cDTI score, which was correlated with the severity of short-term neurological functions.

Effect of intravenous thrombolysis in acute ischemic stroke patients with cerebral microbleeds and analysis of risk factors for hemorrhagic transformation.

To investigate the safety and efficacy of intravenous thrombolysis with recombinant tissue plasminogen activator (rt-PA) in patients with acute ischemic stroke (AIS) and cerebral microbleeds (CMBs) and analyze the risk factors for hemorrhagic transformation (HT). The clinical data of 220 patients with CMB within the first 4.5 h after the onset of acute ischemic stroke treated in our hospital from September 2018 to December 2019 were retrospectively analyzed. Then, these patients were evenly assigned into two groups based on whether the intravenous thrombolysis with rt-PA was adopted or not. Next, the neurological deficit was scored using the National Institute of Health stroke scale (NIHSS) before and after treatment, the modified Rankin scale (mRs) score of patients was recorded at 90 d after treatment, and the incidence rate and death rate of intracranial hemorrhage (ICH) after treatment were recorded and evaluated. Additionally, the univariate and logistic regression analyses were employed for the risk factors for HT in patients after thrombolysis. The NIHSS score declined to (7.08±3.75) points and (7.83±4.22) points at 24 h after treatment and (3.67±3.63) points and (4.92±3.87) points at 7 d after treatment, respectively, in Thrombolysis group and Control group, which were significantly lower than those before treatment (p<0.05). The NIHSS score displayed no statistically significant difference between the two groups at 24 h after treatment (p=0.165), whereas it was markedly lower in Thrombolysis group than that in Control group at 7 d after treatment (p=0.015). At 90 d after treatment, there were 98 (89.1%) and 79 (71.8%) cases of good prognosis in Thrombolysis group and Control group, respectively, and the difference was statistically significant between the two groups (p=0.002). Besides, the number of patients with SICH and aSICH was 3 and 2 (2.7% vs. 1.8%, p=0.651) and 9 and 4 (8.2% vs. 3.6%, p=0.152) in Thrombolysis group and Control group, respectively, and the number of deaths was 7 and 5 (6.4% vs. 4.5%, p=0.553) in the two groups, showing no statistically significant difference. The results of univariate and multivariate analyses revealed that the time from stroke onset to thrombolysis, baseline NIHSS score, and history of atrial fibrillation were independent risk factors affecting the HT of patients undergoing intravenous thrombolysis [odds ratio (OR) =1.330, 95% confidence interval (95% CI) =1.079-1.851, p=0.019; OR=1.592, 95% CI=1.025-2.767, p=0.010; OR=2.428, 95% CI=1.814-3.643, p=0.016]. Compared with those undergoing no intravenous thrombolysis with rt-PA, patients with acute ischemic stroke and CMB who received intravenous thrombolysis with rt-PA exhibit significantly improved short-term neurological function recovery and long-term prognosis, but the incidence and mortality rates of ICH have no statistically significant differences. Moreover, the time from stroke onset to thrombolysis, baseline NIHSS score, and history of atrial fibrillation are independent risk factors affecting the HT of patients treated with intravenous thrombolysis.

Inhibition of immunoproteasome subunit low molecular mass polypeptide 7 with ONX-0914 improves hypoxic-ischemic brain damage via PI3K/Akt signaling.

The immunoproteasome subunit low molecular mass polypeptide 7 (LMP7) leads to brain injuries, such as autoimmune neuritis and ischemic stroke, by activating inflammation. However, the roles and mechanisms of LMP7 in hypoxic-ischemic brain damage (HIBD) remain unclear. This study explored these issues in a rat model of HIBD. Pathology was evaluated using hematoxylin-eosin staining. LMP7 expression was detected using western blot analysis, reverse transcription-quantitative PCR (RT-qPCR), and immunohistochemical staining. The presence of proinflammatory cytokines, including tumor necrosis factor-a, interleukin-6, and interleukin-1β, was tested using ELISA and RT-qPCR. Behavioral performance was evaluated using a short-term neurological function score and the Morris water maze test. Compared to those in the Sham group, the HIBD group exhibited obvious upregulated LMP7 and pro-inflammatory cytokine levels. HIBD rats exhibited severe pathological and behavioral damage. LMP7 inhibition with ONX-0914 reduced proinflammatory cytokine expression, attenuated pathological damage, and enhanced behavioral performance of rats with HIBD. Inhibition of phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) signaling with LY29400 increased LMP7 expression and abolished the protective effects of ONX-0914 in HIBD rats. Our findings indicate that LMP7 aggravates brain injury by triggering inflammatory responses in HIBD rats. LMP7 inhibition with ONX-0914 exerts protective effects on HIBD rats, possibly via PI3K/Akt signaling.

Naoxueshu relieves hematoma after clot removal in acute spontaneous intracerebral hemorrhage.

ObjectivesSurgical treatment is expected to remove clot immediately in acute spontaneous intracerebral hemorrhage (SICH) patients. The aim of this study was to evaluate whether Naoxueshu could enhance the efficacy of clot removal surgery in acute SICH patients.MethodsOne hundred twenty patients who had been diagnosed as SICH according to neuroimaging were enrolled in this study. They received craniotomy, decompressive craniectomy, or minimally invasive surgical evacuation as appropriate and then were randomized into two groups: the Naoxueshu group (NXS group, n = 60) and the control group (n = 60). All the patients received standard medical management while patients in NXS group also took Naoxueshu oral liquid 10 ml with three times a day for seven consecutive days. The primary outcome was the 7‐day hematoma volume and secondary outcomes were 7‐day National Institutes of Health Stroke Scale (NIHSS) score and 7‐day cerebral edema score.ResultsAfter clot removal surgery, hematoma volume in NXS group (9.5 ± 8.0) was significantly decreased than that in Control group (21.3 ± 22.9, p < .0001) 7 days after surgery. Moreover, cerebral edema was also relieved after 7‐day's Naoxueshu treatment (2.5 ± 0.9 vs. 2.9 ± 0.7, p = .043). Since patients in NXS group had worse baseline NIHSS score (17.2 ± 8.1 vs. 13.7 ± 10.1, p = .039), it was reasonable to conclude that Naoxueshu treatment could improve patients’ neurological function because 7‐day NIHSS score of the two groups was similar.ConclusionNaoxueshu oral liquid could relieve hematoma volume and cerebral edema after clot removal surgery in acute SICH patients. Moreover, it had the potential to improve patients’ short‐term neurological function.

Mechanisms Underlying Abnormal Expression of lncRNA H19 in Neonatal Hypoxic-Ischemic Encephalopathy.

Hypoxic-ischemic (HI)-related brain injury, especially HI encephalopathy (HIE) is a leading cause of morbidity and disability in newborns. Long noncoding RNAs (lncRNAs) are implicated in the progress of HI brain damage. However, the mechanisms underlying the regulatory effects of lncRNA H19 on autophagy in HIE remain unknown. This study was designed to identify the potential mechanisms involving lncRNA H19 in HIE. We selected three HIE newborns and three healthy newborns for neonatal behavioral neurological assessment and screened the differentially expressed lncRNAs by microarray analysis and detected H19 expression in serum. After that, neonatal HIE rats were established and injected with H19 overexpression lentivirus vector or autophagy activator Rapa. The structure and apoptotic levels of brain tissue were observed, and righting reflex and geotaxis reflex were utilized to evaluate the short-term neurological function of HIE rats. The Morris water maze was performed to measure the long-term neurological functions of HIE rats. The binding relationships among H19/miR-19b/protein kinase B3 (Akt3) were verified. Levels of Akt3- and autophagy-related proteins were measured. H19 was upregulated in HIE newborns and rat models. The areas of cerebral infarction and apoptosis in neonatal HIE rats were increased, and the nerve functions were compromised. The overexpression of H19 alleviated nerve damage of neonatal HIE rats, and reduced autophagy of brain tissue. H19 upregulated Akt3 as a miR-29b sponge. The protective effects of overexpression of H19 on brain tissue and nerve functions of neonatal HIE rats were partially reversed by autophagy activator. H19 improved the brain tissue and alleviated nerve damage of neonatal HIE rats by upregulating the Akt3/mTOR pathway as a miR-29b sponge. · H19 overexpression reduces the nerve damage in neonatal HIE rats.. · H19 reduces autophagy in neonatal HIE rats by the miR-29b/Akt3/mTOR axis.. · Autophagy activator reverses the protection of H19 in neonatal HIE..

Annexin A1 attenuates neuroinflammation through FPR2/p38/COX-2 pathway after intracerebral hemorrhage in male mice.

Spontaneous intracerebral hemorrhage (ICH) is the deadliest stroke subtype and neuroinflammation is a critical component of the pathogenesis following ICH. Annexin A1-FPR2 signaling has been shown to play a protective role in animal stroke models. This study aimed to assess whether Annexin A1 attenuated neuroinflammation and brain edema after ICH and investigate the underlying mechanisms. Male CD-1 mice were subjected to collagenase-induced ICH. Annexin A1 was administered at 0.5hr after ICH. Brain water content measurement, short-term and long-term neurobehavioral tests, Western blot and immnunofluorescence were performed. Results showed that Annexin A1 effectively attenuated brain edema, improved short-term neurological function and ameliorated microglia activation after ICH. Annexin A1 also improved memory function at 28days after ICH. However, these beneficial effects were abolished with the administration of FPR2 antagonist Boc-2. Furthermore, AnxA1/FPR2 signaling may confer protective effects via inhibiting p38-associated inflammatory cascade. Our study demonstrated that Annexin A1/FPR2/p38 signaling pathway played an important role in attenuating neuroinflammation after ICH and that Annexin A1 could be a potential therapeutic strategy for ICH patients.

Efficacy of Solitaire Stent Arterial Embolectomy in Treating Acute Cardiogenic Cerebral Embolism in 17 Patients.

BackgroundThrombolysis with rtPA is the only accepted drug therapy for acute ischemic stroke. Since acute cerebral stroke is so pervasive, newly developed recanalization methods have the potential for wide-ranging impacts on patient health and safety. We explored the efficacy and safety of Solitaire stent arterial embolectomy in the treatment of acute cardiogenic cerebral embolism.Material/MethodsBetween October 2012 and June 2015, 17 patients underwent Solitaire stent arterial embolectomy, either alone or in combination with rtPA intravenous thrombolysis, to treat acute cardiogenic cerebral embolism. Sheath placement time, vascular recanalization time, number of embolectomy attempts, and IV rtPA dose and time were recorded. Success and safety of the recanalization procedure, as well as clinical outcomes, were assessed. These results were compared to 16 control patients who were treated using only rtPA IV thrombolysis.ResultsFull recanalization of the occluded arteries was achieved in 15 (88.2%) of the Solitaire stent patients. NIH Stroke Scale scores of embolectomy patients improved by an average of 12.59±8.24 points between admission and discharge, compared to 5.56±5.96 in the control group (P<0.05). Glasgow Coma Score improvement between admission and discharge was also significantly higher in the embolectomy group (P<0.05). There was no significant difference in symptomatic intracerebral hemorrhage, high perfusion encephalopathy, incidence of hernia, or mortality between the 2 groups (P>0.05).ConclusionsSolitaire stent embolectomy is a safe and effective alternative to simple venous thrombolytic therapy, and it can significantly improve short-term neurological function and long-term prognosis in acute cardiogenic cerebral embolism.

Abstract 292: Comparison of Pharmacological and Physical Hypothermia in Cerebral and Myocardial Function in a Porcine Model of Cardiac Arrest and Resuscitation

Objective: Non-selective cannabinoid (CB) 1/2 receptor agonist, WIN 55,212-2, has been demonstrated to produce pharmacological hypothermia and improved outcomes of CPR in a rat model. In this study, we compared the effects of pharmacological hypothermia induced by WIN 55,212-2 and physical hypothermia by surface cooling in myocardial and neurological function in a porcine model of CPR. Hypothesis: Pharmacological hypothermia by WIN 55,212-2 produced the similar or better cerebral and myocardial function as surface cooling. Methods and results:Ventricular fibrillation (VF) was induced in 14 male domestic pigs weighing between 35 ± 2 kg. CPR was initiated after 7 min of untreated VF. Defibrillation was attempted after 5 min of CPR. If ROSC was not achieved, two mins of CPR was continued and sequenced with defibrillation attempt until ROSC or for a total of 15 mins. At 5 min post resuscitation, animals are randomized to receive intravenous infusion with WIN 55,212-2 at a dose of 1.0 mg/kg/h or surface cooling until blood temperature cooled down to 34 celcius degree and maintained for 4 hrs. When compared to the animals treated with surface cooling, significantly improvement in neurological alertness score (NAS) was observed in the WIN 55,212-2 treated animals at 24 and 48 hrs, but not at 72 hrs (WIN 55,212-2 vs surface cooling: 24 hrs, 93 ± 5 vs 77 ± 12, p&lt;0.01; 48 hrs, 100 ± 0 vs 93 ± 6, p=0.01) (Figure 1A). As to the post resuscitation myocardial function, there was no significant difference in ejection fraction (EF) between these two groups (Figure 1B). Conclusions: Pharmacological hypothermia induced by WIN 55,212-2 exerted better post resuscitation short-term neurological function than physical hypothermia with the similar post resuscitation myocardial function.

Safety of Induced Hypertension Therapy in Patients With Acute Ischemic Stroke

The management of blood pressure in acute stroke is controversial. Small pilot studies have suggested that blood pressure augmentation improves short-term neurological function, but the rate of adverse events with induced hypertension (IH) therapy is unknown. We reviewed 100 consecutive patients who underwent perfusion magnetic resonance imaging for acute ischemic stroke. IH therapy was employed in 46 patients and standard therapy (ST) in 54. The two groups had similar baseline characteristics, but more patients in the IH group had significant large-artery stenoses. The IH group achieved significantly higher mean arterial pressure (MAP) than the ST group within 3 days of initiation of therapy with a variety of vasopressor agents. Only 35% of patients in the IH group actually achieved the target MAP augmentation of 10-20% above baseline, however. All patients survived to discharge. Four patients experienced major adverse events in each group. Two patients in the IH group experienced intra cerebral hemorrhage compared to none in the ST group. Two patients in the ST group experienced myocardial ischemia, compared to none in the IH group. The National Institutes of Health Stroke Scale during the hospitalization and place of discharge were similar in both groups. Patients in the IH group were more likely to be admitted to the intensive care unit and had a longer hospital stay by nearly 4 days compared to the ST group. These data demonstrate the relative safety of IH therapy in acute stroke patients. Given the greater use of resources, however, the role of IH in improving clinical outcomes requires a prospective, randomized trial.