Downregulating PTBP1 fails to convert astrocytes into hippocampal neurons and to alleviate symptoms in Alzheimer's mouse models.

Conversion of astroglia into functional neurons has been considered as a promising therapeutic strategy for neurodegenerative diseases. Recent studies reported that downregulation of the RNA binding protein, PTBP1, converts astrocytes into neurons in situ in multiple mouse brain regions, consequently improving pathological phenotypes associated with Parkinson's disease, RGC loss, and aging. Here, we demonstrate that PTBP1 downregulation using an astrocyte specific AAV-mediated shRNA system fails to convert hippocampal astrocytes into neurons in both male and female WT, and ß-amyloid (5×FAD) and tau (PS19) Alzheimer's disease (AD) mouse models, and fails to reverse synaptic/cognitive deficits and AD-associated pathology in male mice. Similarly, PTBP1 downregulation cannot convert astrocytes into neurons in the striatum and substantia nigra in both male and female WT mice. Together, our study suggests that cell fate conversion strategy for neurodegenerative disease therapy through manipulating one single gene, such as PTBP1, warrants more rigorous scrutiny.Significance Statement:Our results do not support some of the recent extraordinary and revolutionary claims that resident astrocytes can be directly and efficiently converted into neurons. Our study is critical for the field of neural regeneration and degeneration. In addition, our study is financially important because it may prevent other researchers/organizations wasting a vast amount of time and resources on the relevant investigations.

Prognostic Value of Red Blood Cell Distribution Width and Hemoglobin in Patients with Spontaneous Intracerebral Hemorrhage.

BACKGROUND: The association between baseline red blood cell distribution width (RDW) and hemoglobin levels and outcomes after acute intracerebral hemorrhage (ICH) is not well studied. We aimed to investigate the association between baseline RDW and hemoglobin levels with early hematoma expansion (HE) and mortality at 3 months and 1 year in acute ICH patients. METHODS: A total of 393 ICH patients from January 2014 to February 2019 were included. Patients were divided into four groups based on quartiles of RDW and hemoglobin levels at admission, respectively. Logistic regression models were used to estimate the effect of the levels of RDW and hemoglobin on early HE (absolute hematoma growth >6 mL from baseline to follow-up) and allcaused mortality at 3 months and 1 year. RESULTS: There were no significant associations between baseline RDW and hemoglobin levels and early HE. The 3-month mortality (adjusted odds ratio [OR] 2.88; 95% confidence intervals [CI] 0.96-8.64) and 1-year mortality (adjusted OR 3.16, 95% CI 1.08-9.21) was significantly higher in patients with the highest RDW level (Q4) compared to those with the lowest RDW level (Q1). Moreover, patients with the lowest hemoglobin level were significantly associated with increased odds of all-cause mortality at 3-month (adjusted OR 3.95, 95% CI 1.26-12.4) and 1-year (adjusted OR 4.42, 95% CI 1.56-12.5) compared to those with highest hemoglobin level. CONCLUSION: In patients with acute ICH, a higher level of RDW at admission significantly increased the risk of all-cause mortality at 1 year. Moreover, a decreased hemoglobin level at admission was also associated with a higher risk of all-cause mortality at 3 months and 1 year.

Higher NT-proBNP Levels are Related to Poor Functional Outcome and Pneumonia in Acute Intracerebral Hemorrhage Patients.

BACKGROUND: We investigated the association between N-Terminal Pro-B-Type Natriuretic Peptide (NT-proBNP) levels upon hospital admission and early hematoma growth (HG), inhospital pneumonia and major disability in patients with acute intracerebral hemorrhage (ICH). METHODS: A total of 353 ICH patients from January 2014 to February 2019 were included in the present study. Patients were divided into three groups based on the admission NT-proBNP levels (T1: <61; T2: 61-199; T3: ≥199 pg/mL). Logistic regression models were used to estimate the effect of NT-proBNP on early HG, in-hospital pneumonia, and major disability upon hospital discharge (modified Rankin Scale score ≥5) in ICH patients. RESULTS: There was no significant association observed between baseline NT-proBNP levels and early HG (P-trend =0.249). The risk of in-hospital pneumonia was significantly higher in patients with the highest NT-proBNP level (T3) (adjusted odds ratio [OR] 2.13; 95% confidence interval [CI], 1.11-4.08) and higher NT-proBNP level (T2) (adjusted OR 2.18; 95% CI, 1.19-4.00) compared to those with lowest NT-proBNP level (T1). The highest NT-proBNP level (T3) was associated with a 3.55-fold increase in the risk of major disability at hospital discharge (adjusted OR 3.55; 95% CI, 1.23-10.26; P-trend =0.013) in comparison to T1 after adjustment for potential covariates, including pneumonia. CONCLUSION: Increased NT-proBNP at admission was independently associated with in-hospital pneumonia and major disability upon discharge but not early hematoma growth in acute ICH patients.