Berislav Zlokovic

Editorial Expression of Concern: Activated protein C inhibits tissue plasminogen activator-induced brain hemorrhage Editorial Expression of Concern: Activated protein C inhibits tissue plasminogen activator-induced brain hemorrhage Nat Med. 2024 Mar 20. doi: 10.1038/s41591-024-02911-0. Online ahead of print. Authors Tong Cheng # 1 , Anthony L Petraglia # 1 , Zhang Li 2 , Meenakshisundaram Thiyagarajan 1 , Zhihui Zhong 1 , Zhenhua Wu 1 , Dong Liu 1 , Sanjay B Maggirwar 3 , Rashid Deane 1 , José A Fernández 4 , Barbra LaRue 1 , John H Griffin 4 , Michael Chopp 2 , Berislav V Zlokovic 5 Affiliations 1 Department of Neurosurgery, Frank P. Smith Laboratory for Neuroscience and Neurosurgical Research, University of Rochester Medical Center, Rochester, 14642, New York, USA. 2 Department of Neurology, Henry Ford Health Sciences Center, Detroit, 48202, Michigan, USA. 3 Department of Microbiology …

The published β3-tubulin blots shown in Fig. 1b are in error. When preparing Fig. 1b, copies of the vWF blots were incorrectly placed into the positions labeled for β3-tubulin. The raw original blots for vWF and β3-tubulin were correctly included in Supplementary Fig. 14. We have replaced the β3-tubulin blots in Fig. 1b using their correct raw original blots as shown originally in Supplementary Fig. 14.The PICALM blot in Fig. 1b for microvessel-depleted brain samples is in error, as is its corresponding raw original blot shown in Supplementary Fig. 14. An incorrect blot scan was mistakenly used for the microvessel-depleted brain PICALM blots in Fig. 1b. We also made a mistake in Supplementary Fig. 14, as the corresponding raw original blot for PICALM microvessel-depleted brain was incorrect. The PICALM microvessel-depleted brain blot in Fig. 1b and corresponding full blot in Supplementary Fig. 14 have been …

“We determined that there were similarities between the Akt loading control blots in Fig. 2C and the β-actin loading control blots in Fig. 5E, which was due to a mistake in the selection of the Akt control blots for Fig. 2C during manuscript preparation. Since we do not have the original Western blots used in Fig. 2C from approximately 15 years ago, we repeated the experiment shown in Fig. 2C and obtained similar results. Although the error was only in the original Akt control blot, all three blots shown in Fig. 2C were repeated so that the quantification of pGSK3α/β abundance could be correctly normalized to the matching new Akt control blots, following the methods described in the original paper. The corrected Fig. 2C is shown below. For clarity, we also present 3 full blots generated and used for quantification when we repeated the experiment. We sincerely apologize for this unintentional error.”

BackgroundThe disruption of the neurovascular unit (NVU), which maintains the integrity of the blood brain barrier (BBB), has been identified as a critical mechanism in the development of cerebrovascular and neurodegenerative disorders. However, the understanding of the pathophysiological mechanisms linking NVU dysfunction to the disorders is incomplete, and reliable blood biomarkers to measure NVU dysfunction are yet to be established. This systematic review and meta-analysis aimed to identify biomarkers associated with BBB dysfunction in large vessel disease, small vessel disease (SVD) and vascular cognitive disorders (VCD).MethodsA literature search was conducted in PubMed, EMBASE, Scopus and PsychINFO to identify blood biomarkers related to dysfunction of the NVU in disorders with vascular pathologies published until 20 November 2023. Studies that assayed one or more specific markers …

BackgroundCerebral edema is a secondary complication of acute ischemic stroke, but its time course and imaging markers are not fully understood. Recently, net water uptake (NWU) has been proposed as a novel marker of edema.AimsStudying the RHAPSODY trial cohort, we sought to characterize the time course of edema and test the hypothesis that NWU provides distinct information when added to traditional markers of cerebral edema after stroke by examining its association with other markers.MethodsA total of 65 patients had measurable supratentorial ischemic lesions. Patients underwent head computed tomography (CT), brain magnetic resonance imaging (MRI) scans, or both at the baseline visit and after 2, 7, 30, and 90 days following enrollment. CT and MRI scans were used to measure four imaging markers of edema: midline shift (MLS), hemisphere volume ratio (HVR), cerebrospinal fluid (CSF …

Diffuse white-matter disease associated with small-vessel disease and dementia is prevalent in the elderly. The biological mechanisms, however, remain elusive. Using pericyte-deficient mice, magnetic resonance imaging, viral-based tract-tracing, and behavior and tissue analysis, we found that pericyte degeneration disrupted white-matter microcirculation, resulting in an accumulation of toxic blood-derived fibrin(ogen) deposits and blood-flow reductions, which triggered a loss of myelin, axons and oligodendrocytes. This disrupted brain circuits, leading to white-matter functional deficits before neuronal loss occurs. Fibrinogen and fibrin fibrils initiated autophagy-dependent cell death in oligodendrocyte and pericyte cultures, whereas pharmacological and genetic manipulations of systemic fibrinogen levels in pericyte-deficient, but not control mice, influenced the degree of white-matter fibrin(ogen) deposition …

The authors have retracted this article after concerns were raised about some of the data reported. Similarities were identified between representative image panels in Fig. 7, which shows tissue staining with four different anti-tau antibodies:• Fig. 7e and 7f (hippocampus in control AppSW/0 Pdgfrb+/+ mice) images show similarities in negative staining for tau on tissue sections with two different tau antibodies.• Fig. 7e and 7f (hippocampus in pericyte-deficient AppSW/0 Pdgfrb+/− mice) images show similarities in positive staining for tau on tissue sections with two different tau antibodies.• Fig. 7a and 7e (hippocampus in control AppSW/0 Pdgfrb+/+ mice) images show similarities in negative staining for tau on tissue sections with two different tau antibodies.

The published article contained an error in the western blot image in Figure 4A. The C5 and C5o strips were duplicate images of the same blot. Due to lack of clear and adequate labeling of the original images, we are not able to determine with confidence which protein each of the strips and condition each lane in this figure and the original blots represent. Therefore, we have removed the western blot analysis (Figure 4A and the accompanying graphs Figure 4B–E) from the article. In addition, the description of the western blot was removed from the “Methods” section and the Figure 4 caption. In the “Methods” section, in the “Study Design” subsection, the fifth sentence of the third paragraph was changed from “However, multiple markers of white matter injury [KB, dMBP, T2 weighted magnetic resonance imaging (MRI)], inflammation (Iba-1, GFAP, C5, C5o, CD88, TLR4), and oxidative stress (8-OHdG, nitrate, nitrite …