We investigated levels of the β-amyloid 1–42 (Aβ42), total tau protein (T-tau) and tau phosphorylated at position threonine 181 (P-tau) in cerebrospinal fluid (CSF) of idiopathic normal pressure hydrocephalus (iNPH) patients and tried to find their clinical implications in the evaluation and treatment of iNPH. Twenty-five possible iNPH patients were prospectively enrolled and their CSF was collected to analyze levels of Aβ42, T-tau and P-tau using ELISA method. Gait disturbance, urinary incontinence, and cognitive impairment were semi-quantified and detailed neuropsychological (NP) test was performed. Eight iNPH patients were classified into the lower CSF Aβ42 group and 17 patients were classified into the higher CSF Aβ42 group. There was no difference in the iNPH grading score and its improvement after LP between the two groups. The lower CSF Aβ42 group showed more deficits in attention, visuospatial function and verbal memory in the baseline NP test and less improvement in phonemic categorical naming and frontal inhibitory function after LP. Our study suggested that concomitant AD in iNPH patients might contribute to lumbar puncture or shunt unresponsiveness, especially in the field of cognitive dysfunction.

Background: To establish an easy and rapid method for evaluating pial collateral flow, we compared the Alberta Stroke Program Early CT Score (ASPECTS) on nonenhanced CT (NECT), conventional contrast-enhanced CT (CECT), and CT angiography source images (CTA-SI) in patients with acute ischemic stroke. Methods: We reviewed 55 consecutive patients with acute ischemic stroke involving the anterior circulation who underwent thrombolysis within 6 h of referral to the stroke center. We evaluated axial images using NECT, CECT and CTA-SI. Pial collateral formation was graded as fair (1–2 points) or bad (3–5 points) based on 4-vessel angiography. The outcomes were dichotomized into good (modified Rankin Scale, mRS 0–2) or poor (mRS 3–6) using a 90-day mRS. Results: Demographics (age, sex, initial National Institutes of Health Stroke Scale score, time to CT acquisition and stroke subtypes) did not significantly differ between patients with fair or bad collateral formation. ASPECTS on CECT (r = –0.788, p < 0.0001) was more inversely correlated with pial collateral formation than ASPECTS on NECT (r = –0.557, p < 0.0001) or ASPECTS on CTA-SI (r = –0.662, p < 0.0001). Furthermore, ASPECTS on CECT demonstrated a high discriminative capability, with an area under the receiver operating characteristic curve of 0.885 for fair collateral circulation, compared to 0.790 for ASPECTS on NECT and 0.794 for ASPECTS on CTA-SI. Multiple regression analysis revealed that ASPECTS on CECT (≧8) was an independent predictor for fair collateral circulation (odds ratio = 23.00, p < 0.001) and a good prognosis (odds ratio = 17.81, p < 0.001). Conclusion: ASPECTS on CECT is a feasible method for predicting pial collateral flow and overall outcomes in acute ischemic stroke.

Significance: Ischemic stroke in white matter induces degeneration of oligodendrocytes (OLs) and myelin. How ischemia leads to white matter degeneration remains elusive, and there is therefore no specific treatment to prevent ischemic white matter damage. Here we provide evidence that HMGB1 released from ischemic OLs may provide TLR2-dependent autocrine trophic effects on neighboring OLs. Injection of an HMGB1 inhibitor exacerbated the structural and functional outcomes in a focal white matter stroke model, suggesting a function for HMGB1 as an endogenous trophic factor for OLs and myelin sheath under ischemia. Thus, our study identified HMGB1 as a stress-induced signal that maintains structural and functional integrity of the white matter and provides a target for therapeutic development in white matter stroke.

This study aimed to evaluate the sensitivity and prognostic value of arterial spin labeling (ASL) in a large group of status epilepticus (SE) patients and compare them with those of other magnetic resonance (MR) sequences, including dynamic susceptibility contrast (DSC) perfusion imaging. We retrospectively collected data of patients with SE in a tertiary center between September 2016 and March 2020. MR images were visually assessed, and the sensitivity for the detection of SE and prognostication was compared among multi-delay ASL, DSC, fluid-attenuated inversion recovery (FLAIR), and diffusion-weighted imaging (DWI). We included 51 SE patients and 46 patients with self-limiting seizures for comparison. Relevant changes in ASL were observed in 90.2% (46/51) of SE patients, a percentage higher than those for DSC, FLAIR, and DWI. ASL was the most sensitive method for initial differentiation between SE and self-limiting seizures. The sensitivity of ASL for detecting refractory SE (89.5%) or estimating poor outcomes (100%) was higher than those of other MR protocols or electroencephalography and comparable to those of clinical prognostic scores, although the specificity of ASL was very low as 9.4% and 15.6%, respectively. ASL showed a better ability to detect SE and predict the prognosis than other MR sequences, therefore it can be valuable for the initial evaluation of patients with SE.

Background: The migration of oligodendrocyte precursor cells (OPC) is a key process of remyelination, which is essential for the treatment of white matter stroke. This study aimed to investigate the role of HMGB1 (high mobility group box 1), a damage-associated molecular pattern released from dying oligodendrocytes, as an autocrine chemoattractant that promotes OPC migration. Methods: The migratory capacity of primary cultured OPCs was measured using the Boyden chamber assay. The downstream pathway of HMGB1-mediated OPC migration was specified by siRNA-induced knockdown or pharmacological blockade of TLR2 (toll-like receptor 2), RAGE (receptor for advanced glycation end product), Src, ERK1/2 (extracellular signal-regulated kinase1/2), and FAK (focal adhesion kinase). Conditioned media were collected from oxygen-glucose deprivation-treated oligodendrocytes, and the impact on OPC migration was assessed. Lesion size and number of intralesional Olig2(+) cells were analyzed in an in vivo model of white matter stroke with N5-(1-iminoethyl)-L-ornithine (L-NIO). Results: HMGB1 treatment promoted OPC migration. HMGB1 antagonism reversed such effects to untreated levels. Among the candidates for the downstream signal of HMGB1-mediated migration, the knockdown of TLR2 rather than that of RAGE attenuated the migration-promoting effect of HMGB1. Further specification of the HMGB1-TLR2 axis revealed that the phosphorylation of ERK1/2 and its downstream molecule FAK, rather than of Src, was decreased in TLR2-knockdown OPCs, and pharmacological inhibition of ERK1/2 and FAK led to decreased OPC migration. Oxygen-glucose deprivation-conditioned media promoted OPC migration, suggesting the autocrine chemoattractant function of HMGB1. In vivo, TLR2(−/−)-mice showed lesser intralesional Olig2(+) cells compared to wild-type controls in response to L-NIO induced ischemic injury regardless of HMGB1 administration. Conclusions: HMGB1, through the TLR2-ERK1/2-FAK axis, functions as an autocrine chemoattractant to promote OPC migration, which is an initial and indispensable step in remyelination. Thus, a novel treatment strategy for white matter stroke based on the HMGB1-TLR2 axis in the oligodendrocyte lineage could be feasible.