Post-stroke Chinese pure alexia: linguistic features and neuropsychological profiles.

PURPOSE: Very few cases of Chinese pure alexia have been reported to date. We aim to summarize the linguistic features and neuropsychological profiles of Chinese pure alexia through a case series study. METHODS: 11 consecutive patients with post-stroke Chinese pure alexia and 11 healthy controls were included. The Aphasia Battery of Chinese (ABC) and 68-Chinese character oral reading test (68-character test) were used to evaluate the reading and writing ability. Reading errors were classified based on the performance of 68-character test. Neuropsychological profiles were evaluated with corresponding scales. The possible correlation between the reading ability and the writing ability or neuropsychological performance was analyzed. RESULTS: The patients had a correct rate of 43.7 ± 23.2% in the 68-character test, significantly lower (P < 0.001) than that of controls. Shape-similar error was the most common type of reading error (101/209, 48.3%). The ABC total writing score rate of the patients ranged from 68.9% to 98.7% (median, 90.5%), significantly lower (P < 0.001) than that of the controls. The patients also showed worse performance in MMSE, auditory verbal learning test, Boston naming test, intersecting pentagons copying and clock-drawing test (all P < 0.05). In the patient group, the correct rate of 68-character test was significantly correlated with the ABC total writing score rate (P = 0.008), the score rate of Boston naming test (P = 0.017), and the clock-drawing test score (P = 0.010). CONCLUSION: Shape-similar errors may be a characteristic of Chinese pure alexia. The correlation between visuospatial dysfunction and pure alexia might explain the frequent occurrence of shape-similar errors in Chinese pure alexia.

Differential second messenger signaling via dopamine neurons bidirectionally regulates memory retention.

Memory formation and forgetting unnecessary memory must be balanced for adaptive animal behavior. While cyclic AMP (cAMP) signaling via dopamine neurons induces memory formation, here we report that cyclic guanine monophosphate (cGMP) signaling via dopamine neurons launches forgetting of unconsolidated memory in Drosophila. Genetic screening and proteomic analyses showed that neural activation induces the complex formation of a histone H3K9 demethylase, Kdm4B, and a GMP synthetase, Bur, which is necessary and sufficient for forgetting unconsolidated memory. Kdm4B/Bur is activated by phosphorylation through NO-dependent cGMP signaling via dopamine neurons, inducing gene expression, including kek2 encoding a presynaptic protein. Accordingly, Kdm4B/Bur activation induced presynaptic changes. Our data demonstrate a link between cGMP signaling and synapses via gene expression in forgetting, suggesting that the opposing functions of memory are orchestrated by distinct signaling via dopamine neurons, which affects synaptic integrity and thus balances animal behavior.

Predictors of hemodynamic instability during and persistent after carotid artery stenting.

OBJECTIVES: The risk factors for post-carotid artery stenting severe hemodynamic instability remain elusive. This study aimed to identify the predictors of severe hemodynamic instability during and persisted after carotid artery stenting. MATERIALS AND METHODS: Consecutive patients who underwent carotid artery stenting for extracranial carotid artery stenosis at a single-center between September 2018 and July 2021 were retrospectively assessed. The predictive factors of severe hemodynamic instability intraoperation and post-operation were analyzed. RESULTS: Among the 139 patients included, 63 experienced severe hemodynamic instability, with 45 and 18 cases occurring intra and postoperatively, respectively. Persistent was observed in 21 patients. Smoke exposure (odds ratio [OR], 2.38; p=0.039), carotid bifurcation stenosis (OR, 0.91; p=0.018), and large-diameter balloon (>4 mm) dilatation (OR, 11.95; p<0.001) were identified as independent risk factors for hemodynamic instability at any stage of carotid artery stenting. Intraoperatively, large-diameter balloon (>4 mm) dilatation was associated with an increased risk of hemodynamic instability occurrence (OR, 4.67; p=0.01), whereas general anesthesia (OR, 0.19; p=0.001) and a longer distance from the stenosis to the carotid bifurcation (OR, 0.89; p=0.01) were negatively associated with hemodynamic instability. Furthermore, smoking exposure (OR, 3.73; p=0.03), large diameter balloon dilatation (OR, 6.12; p=0.032), distance from stenosis to bifurcation (OR, 0.85; p=0.047) and long-stent (40 mm) implantation (OR, 0.84 [95% confidence interval, 0.74-0.95]; p=0.007) could independently predict persistent hemodynamic instability. CONCLUSION: Patients with a smoking history, lesions near the carotid bulb, or dilatation using a large-diameter balloon were most likely to suffer severe hemodynamic instability. General anesthesia can protect against severe hemodynamic instability only intraoperatively. Long-term stent implantation may reduce persistent hemodynamic instability.

Intracranial hypertension due to bilateral internal jugular venous occlusion in eagle syndrome: a case report.

Eagle syndrome is a clinical condition that characterized by myriad of symptoms associated with the compression of neurovascular structures by an elongated styloid process. Herein we describe a rare case of Eagle syndrome who showed bilateral internal jugular venous occlusion duo the compression of the styloid process. A young man presented with headaches for six months. Lumbar puncture showed an opening pressure of 260 mmH2O and the cerebrospinal fluid analysis was normal. Catheter angiography revealed occlusion of bilateral jugular venous. Computed tomography venography demonstrated compression of bilateral jugular venous by bilateral elongated styloid processes. The patient was diagnosed with Eagle syndrome and suggested to undergo styloidectomy, after which he recovered completely. We emphasize that Eagle syndrome is a rare cause of intracranial hypertension and styloid resection can bring an excellent clinical outcome in patents with intracranial hypertension due to Eagle syndrome.

BMP9 ameliorates amyloid pathology by promoting low-density lipoprotein receptor-related protein 1 expression in APP/PS1 transgenic mice.

Alzheimer's disease (AD) is the most common cause of dementia worldwide. Our previous study revealed that bone morphogenetic protein 9 (BMP9) could ameliorate the amyloid pathology and cognitive impairments in a transgenic model of AD. However, the mechanisms underlying the protective effect of BMP9 against amyloid pathology remain unknown. Low-density lipoprotein receptor-related protein 1 (LRP1) plays an essential role in the clearance of amyloid beta. Here, we demonstrated that intranasal BMP9 significantly enhanced the expression of LRP1 in the brains of APP/PS1 mice. Importantly, silencing LRP1 significantly promoted the amyloid plaques accumulation and facilitated the neuroinflammation in the brains of BMP9-treated APP/PS1 mice. Furthermore, silencing LRP1 significantly impaired the learning and memory functions of BMP9-treated APP/PS1 mice. Our results suggest that BMP9 ameliorate the amyloid pathology and cognitive dysfunction in APP/PS1 mice by promoting the expression of LRP1.

A Comparison of Different Endovascular Treatment for Vertebral Artery Origin Stenosis.

OBJECTIVE: To compare the safety and efficacy of stenting with drug-eluting stent (DES), stenting with bare mental stent (BMS), and angioplasty alone with drug-coated balloon (DCB) in patients with symptomatic vertebral artery origin stenosis (VAOS) who did not respond to aggressive medical management. METHODS: We performed a retrospective analysis of consecutive patients with symptomatic VAOS who underwent endovascular treatment between December 2018 and November 2021 at our institution. The main outcome compared were technical success, perioperative complications, residual stenosis, stroke recurrence, progression of residual stenosis, and restenosis. RESULTS: A total of 46 patients were included: 29 were stented with DES, 12 were stented with BMS, and 5 received angioplasty alone with DCB. Technical success was achieved in 100%, 100%, and 60%, respectively (P = 0.008). Residual stenosis was 10.8%, 20.2%, and 51.2%, respectively (P < 0.001). Perioperative complications occurred only in 1 case in the DES group (P = 1.00). During a mean follow-up of 14.1 months, stroke recurrence rate was 6.9%, 16.7%, and 0% respectively (P = 0.73). Absolute progression of residual stenosis was 10.1%, 34.9%, and -8.0%, respectively (P < 0.001). Restenosis rate was 6.9%, 50.0%, and 20.0%, respectively (P = 0.007). CONCLUSIONS: In patients with symptomatic VAOS who did not respond to aggressive medical management, stenting with DES shows superiority in the lowering the restenosis rate compared with stenting with BMS. Angioplasty alone with DCB is associated with the slowest progression of stenosis in spite of moderate residual stenosis.

Sequential tirofiban infusions combined with endovascular treatment may improve outcomes in acute ischemic stroke - a meta-analysis.

In this meta-analysis, we explored whether tirofiban could safely improve outcomes when combined with endovascular therapy in acute ischemic stroke with large vessel occlusion. We searched the PubMed, EMBASE, Web of Science, and The Cochrane Library databases from January 2000 to October 2019 for relevant RCTs/non-RCTs. A total of 13 trials involving 2584 patients, of whom 893 (34.5%) received tirofiban, were ultimately included in the meta-analysis. The results suggested that tirofiban improved patient independence at 90 days (51.2% vs 42.4%; OR 1.26; p =0.02) without increasing the risk of symptomatic intracranial hemorrhage (OR 1.01; p =0.96) or mortality (OR 0.86; p =0.09). There was no association between the use of tirofiban and recanalization rate (OR 1.35; p =0.11). Subgroup analysis showed that a loading dose followed by maintenance doses, but not a single dose, of tirofiban increased favorable 90-day functional outcomes (OR 1.49; p =0.0008). Moreover, low maintenance doses may be more effective than high maintenance doses (OR 1.41; p =0.02). These results suggest that adjunctive tirofiban treatment administered as a loading dose followed by low-dose maintenance may improve functional outcomes of endovascular therapy in acute ischemic stroke.

Nerve growth factor metabolic dysfunction contributes to sevoflurane-induced cholinergic degeneration and cognitive impairments.

General anesthesia with sevoflurane is associated with an increased incidence of postoperative cognitive dysfunction. Previous studies have shown that sevoflurane anesthesia can affect the integrity and function of basal forebrain cholinergic neurons (BFCNs) which are essential for learning and memory. However, the underlying mechanisms remain largely unknown. Here, we demonstrated that exposure to 2.5% sevoflurane induced significant loss of BFCNs and caused impairments of the spatial and the fear memory. Further, sevoflurane exposure significantly reduced the level of nerve growth factor (NGF), an important factor for the survival and phenotype maintenance of BFCNs, by disrupting its synthesis pathways in the brain. More importantly, NGF administration not only prevented the loss of BFCNs but also ameliorated the cognitive impairments in sevoflurane-treated mice. Our findings indicate that NGF metabolic dysfunction contributes to sevoflurane-associated BFCNs degeneration and subsequent cognitive deficits.

The Synergy of Aging and LPS Exposure in a Mouse Model of Parkinson's Disease.

Aging is an inevitable physiological challenge occurring in organisms over time, and is also the most important risk factor of neurodegenerative diseases. In this study, we observed cellular and molecular changes of different age mice and LPS-induced Parkinson disease (PD) model. The results showed that behavioral performance and dopaminergic (DA) neurons were declined, accompanied by increased expression of pro-inflammatory factors (TLR2, p-NF-kB-p65, IL-1ß and TNF-α), as well as pro-oxidative stress factor gp91phox in aged mice compared with young mice. Aging exaggerated inflammatory M1 microglia, and destroyed the balance between oxidation and anti-oxidation. The intranasal LPS instillation induced PD model in both young and aged mice. The poor behavioral performance and the loss of DA neurons as well as TLR2, p-NF-kB-p65, IL-1ß, TNF-α, iNOS and gp91phox were further aggravated in LPS-aged mice. Interestingly, the expression of Nrf2 and HO-1 was up-regulated by LPS only in young LPS-PD mice, but not in aged mice. The results indicate that the synergy of aging process and LPS exposure may prominently aggravate the DA neurons loss caused by more serious neuroinflammation and oxidative stress in the brain.

Suppressor of Cytokine Signaling 3: Emerging Role Linking Central Insulin Resistance and Alzheimer's Disease.

Currently, the etiology of Alzheimer's disease (AD) is still elusive. Central insulin resistance has been determined to play an important role in the progress of AD. However, the mechanism underlying the development of disrupted insulin signaling pathways in AD is unclear. Suppressor of cytokine signaling 3 (SOCS3) is a member of the SOCS protein family that acts as a negative modulator of insulin signaling in sensitive tissues, such as hepatocytes and adipocytes. However, little is known about its role in neurological diseases. Recent evidence indicates that the level of SOCS3 is increased in the brains of individuals with AD, especially in areas with amyloid beta deposition, suggesting that SOCS3 may regulate the central insulin signaling pathways in AD. Here, we discuss the potential role of SOCS3 in AD and speculate that SOCS3 may be a promising therapeutic target for the treatment of AD.

Iron Deposition Leads to Neuronal α-Synuclein Pathology by Inducing Autophagy Dysfunction.

Growing evidence has indicated that iron deposition in the substantia nigra plays an important role in Parkinson's disease (PD). However, the underlying mechanism is still elusive. Using primary dopaminergic neurons and SH-SY5Y cells cultured in vitro, we observed that iron loading increased α-synuclein and reactive oxygen species (ROS) levels in these cells but did not affect the intracellular α-synuclein mRNA levels. Furthermore, iron loading significantly downregulated Beclin-1 levels and decreased the ratio of microtubule-associated protein 1 light chain 3 isoforms (LC3 II/LC3 I). However, a significant change in the levels of autophagy-related gene 5 (Atg5) was not observed in either neurons or SH-SY5Y cells after iron treatment. After treatment with rapamycin, the iron loading-induced increase in the α-synuclein level was significantly reversed and ROS generation was alleviated in both cultured neurons and SH-SY5Y cells. These results indicate that the inhibition of autophagy is critical for the pathological alterations in α-synuclein induced by iron loading. Moreover, treatment with vitamin E did not affect the increase in the α-synuclein levels but significantly eliminated the iron-induced ROS production. Together, our study shows that autophagy dysfunction contributes to iron-induced α-synuclein pathology.

Intranasal BMP9 Ameliorates Alzheimer Disease-Like Pathology and Cognitive Deficits in APP/PS1 Transgenic Mice.

Alzheimer's disease (AD) is the most common type of dementia and has no effective therapies. Previous studies showed that bone morphogenetic protein 9 (BMP9), an important factor in the differentiation and phenotype maintenance of cholinergic neurons, ameliorated the cholinergic defects resulting from amyloid deposition. These findings suggest that BMP9 has potential as a therapeutic agent for AD. However, the effects of BMP9 on cognitive function in AD and its underlying mechanisms remain elusive. In the present study, BMP9 was delivered intranasally to 7-month-old APP/PS1 mice for 4 weeks. Our data showed that intranasal BMP9 administration significantly improved the spatial and associative learning and memory of APP/PS1 mice. We also found that intranasal BMP9 administration significantly reduced the amyloid ß (Aß) plaques overall, inhibited tau hyperphosphorylation, and suppressed neuroinflammation in the transgenic mouse brain. Furthermore, intranasal BMP9 administration significantly promoted the expression of low-density lipoprotein receptor-related protein 1 (LRP1), an important membrane receptor involved in the clearance of amyloid ß via the blood-brain barrier (BBB), and elevated the phosphorylation levels of glycogen synthase kinase-3ß (Ser9), which is considered the main kinase involved in tau hyperphosphorylation. Our results suggest that BMP9 may be a promising candidate for treating AD by targeting multiple key pathways in the disease pathogenesis.

Insulin-like growth factor-1 protects SH-SY5Y cells against ß-amyloid-induced apoptosis via the PI3K/Akt-Nrf2 pathway.

Insulin-like growth factor-1 (IGF-1) shows protective effect against Aß-induced cytotoxicity and apoptosis, but the underlying mechanisms are poorly characterized. The present study was conducted to explore the mechanisms involved in the beneficial effect of IGF-1 against Aß-induced apoptosis in SH-SY5Y cells. We found that pretreatment with IGF-1 attenuated Aß25-35-induced loss of cell viability and apoptosis in SH-SY5Y cells in a dose-dependent manner. In addition, IGF-1 inhibited the generation of reactive oxygen species (ROS) and increased the antioxidant activity in Aß25-35-treated cells. Further, IGF-1 significantly promoted the nuclear translocation of Nrf2, and upregulated the expression of its downstream gene heme oxygenase-1 (HO-1). Moreover, LY294002, a specific PI3K inhibitor, was found to completely abolish the protective effect of IGF-1 on Aß25-35-induced apoptosis and ROS generation. Together, our findings suggest that IGF-1 protects SH-SY5Y cells against Aß25-35-induced cell injury by scavenging ROS via the PI3K/Akt-Nrf2 signaling pathway.