CD4+ T cells from preeclamptic patients cause hypertension, autoantibodies and cognitive dysfunction in a pregnant rat model

CD4+ T Cells from Preeclamptic patients with or without a history of COVID-19 during pregnancy cause hypertension, autoantibodies and cognitive dysfunction in a pregnant rat model Objective: Preeclampsia (PE) new onset hypertension (HTN) during pregnancy, is associated with increased autoantibodies, cerebral blood flow (CBF) impaired cognitive function and memory loss. We have shown adoptive transfer of placentalCD4+T cells from PE women into athymic nude pregnant rats causesHTNand autoantibodies associated with PE.COVID-19 (CV) during pregnancy is associated with increased diagnosis of PE. However, we do not know the role of CD4+ T cells stimulated in response to CV in contributing to the PE phenotype seen patients with a Hx of CV during pregnancy. Therefore, we hypothesize that adoptive transfer of placental CD4+ T cells from patients with a CV History (Hx) during pregnancy with PE causes HTN, increased CBF and cognitive dysfunction in pregnant athymic nude recipient rats. Study Design: Placental CD4+ T cells isolated from normotensive (NP), PE, Hx of CV normotensive (CV Hx NT), and Hx of CV with PE (CV Hx+PE) at delivery. One million CD4+ T cells were injected i.p. into nude athymic rats on gestational day (GD) 12. The Barnes maze and the novel object recognition behavioral assays were used to assess cognitive function on GDs 15-19. Blood pressure (MAP) and CBF were measured by carotid catheter and laser Doppler flowmetry on GD19, respectively. A two-way ANOVA was used for statistical analysis. Result(s):MAPincreased inCVHx+PE (111 +/- 4, n = 4) and PE recipient rats (115 +/- 2 mmHg, n = 5) compared to CV Hx NT (100 +/- 4, n = 5) and NP (99 +/- 3 mmHg, n = 4, P < .05). CV Hx+PE and PE exhibited latency with errors navigating in the Barnes maze compared to CV Hx NT and NP groups. Locomotor activity was decreased in CV Hx+PE (P < .05) compared to PE, CV Hx NT, and NP groups. CV Hx+PE and PE spent more time exploring identical objects compared to CV Hx NT and NP groups. PE and CV Hx+ PE had increased CBF compared to CV Hx NT and NP rats. Conclusion(s): Our findings indicate that pregnant recipients of CD4+ T cells from PE with or without a Hx CV during pregnancy cause HTN, increased CBF and cognitive dysfunction compared to recipients of NP or NT Hx COVID-19 CD4+ T cells.

Asymmetric Cerebral Perfusion in Comatose Extracorporeal Membrane Oxygenation Patients

Asymmetric cerebral perfusion can occur when extracorporeal membrane oxygenation (ECMO) flow competes with native cardiac circulation. It is unclear whether this phenomenon associates with brain injury. Diffuse correlation spectroscopy (DCS) provides continuous, laser-based, non-invasive, bedside monitoring of relative cerebral blood flow (rCBF). This study measured rCBF in ECMO patients via DCS to determine whether comatose patients experience asymmetric cerebral perfusion. Adults receiving ECMO for any indication were prospectively recruited from 12/2019-3/2021. Patients with prior neurologic injury, scalp/facial lacerations, and SARS-CoV-2 infection were excluded. DCS monitoring was performed daily during ECMO support with sensors placed on bilateral foreheads. Mean arterial pressure (MAP) was continuously recorded from the bedside monitor. The Glasgow Coma Scale (GCS) was assessed by clinical staff multiple times daily with sedation pauses, if possible, per standard of care. rCBF was calculated by comparing continuous cerebral blood flow (CBF) measurements to the daily median CBF, then averaged at each MAP value. Daily rCBF asymmetry was calculated by summing the absolute difference of rCBF between the two hemispheres at each MAP value, normalized for the total MAP range experienced by the patient that day. Twelve subjects were enrolled in this study (ages 21-78, 6 with cardiac arrest, 4 with acute heart failure, 2 with ARDS) and grouped by maximum GCS motor (GCS-M) score during ECMO, with 3 "comatose" subjects (GCS-M <= 4), and 9 "awake" subjects (GCS-M > 4). DCS was performed over 66 sessions with a mean duration of 131.83 +/- 1.13 minutes. Comatose subjects exhibited more rCBF asymmetry than awake subjects (0.28 +/- 0.06 mmHg-1 vs. 0.10 +/- 0.001 mmHg-1, p=0.045). No difference in asymmetry was noted between patients with or without cardiac arrest. We found that comatose ECMO subjects exhibited higher inter-hemispheric rCBF asymmetry over a range of blood pressures than awake subjects. Though our comatose sample is small, further validation of this finding and its causes, such as cerebrovascular dysregulation, is warranted.

Superior Cerebellar Artery Dissection in a Patient Diagnosed with Reversible Cerebral Vasoconstriction Syndrome: A Case Report

Arterial dissection is an uncommon complication of reversible cerebral vasocon-striction syndrome (RCVS). We describe the case of a 35-year-old woman with a migraine history who presented with recurrent thunderclap headache and focal neurological signs, including right hemiataxia. She had been diagnosed with COVID-19 disease two weeks earlier. Neuroimaging revealed multifocal stenosis of the posterior circulation arteries and dissection of the right superior cerebellar artery. She improved significantly throughout her one-week hospitalization and maintained only mild ataxia. The interplay between COVID-19 disease, RCVS, and arterial dissection requires further investigation.Copyright © Author(s) (or their employer(s)) and Sinapse 2022.

Increased cerebral blood flow and neuroinflammation post COVID-19

Aim/Introduction: Persisting cerebral symptoms such as fatigue and cognitive dysfunction after Sars-CoV-2 infection are typical for post COVID-19. Positron emission tomography (PET) can contribute to the understanding of post COVID-19 related brain disorders. The aim of this study was to investigate cerebral blood flow (CBF) and neuroinflammation with PET in post COVID-19 patients. Material(s) and Method(s): Data from eight healthy controls (HC) and four subjects with post COVID-19 symptoms were included. At the time of the PET investigation, three subjects had remaining post COVID-19 symptoms, of which one had severe headache. All subjects underwent a 6 min dynamic 15O-water PET scan to measure CBF and a 60 min dynamic 11CPK11195 PET scan to measure neuroinflammation. In addition, all subjects received a T1weighted MRI that was co-registered to the PET images. Parametric images, showing 15O-water CBF and 11CPK11195 binding potential (BPND) at the voxel level, were calculated. Mean total grey matter CBF and BPND values were calculated for all subjects. The co-registered MRI images were normalized to MNI standard space using statistical parametric mapping (SPM12) and the transformation matrices were applied to the respective parametric images. A voxel-wise z-test was performed in SPM12 to compare each 15Owater CBF and 11CPK11195 BPND image from the post COVID-19 patients to the HC CBF and BPND images, respectively. A statistical threshold of p<0.05 was applied. Result(s): Two of the subjects with remaining post COVID-19 symptoms demonstrated a significantly increased CBF in the whole brain compared to the HC. Total grey matter CBF values were 1.27 and 1.41 mL/cm3/min in these two subjects, compared to a mean +/- SD of 0.65 +/- 0.19 mL/cm3/min in the HC group. The subject with persisting headache also showed large clusters of significant increased 11C-PK11195 BPND in the meninges. Mean total grey matter 11CPK11195 BPND values in post COVID-19 subjects were within the range of values in the HC group. The other two subjects did not show increased CBF and no significant increase of 11C-PK11195 BPND. Conclusion(s): Neurological symptoms from post COVID-19 may be due to increased CBF and inflammation. However, further investigations are needed with larger study cohort to better understand the relation between post COVID-19 symptoms and neurological dysfunctions investigated with PET.

Increased cerebral blood flow and neuroinflammation post COVID-19

Aim/Introduction: Persisting cerebral symptoms such as fatigue and cognitive dysfunction after Sars-CoV-2 infection are typical for post COVID-19. Positron emission tomography (PET) can contribute to the understanding of post COVID-19 related brain disorders. The aim of this study was to investigate cerebral blood flow (CBF) and neuroinflammation with PET in post COVID-19 patients. Material(s) and Method(s): Data from eight healthy controls (HC) and four subjects with post COVID-19 symptoms were included. At the time of the PET investigation, three subjects had remaining post COVID-19 symptoms, of which one had severe headache. All subjects underwent a 6 min dynamic 15O-water PET scan to measure CBF and a 60 min dynamic 11CPK11195 PET scan to measure neuroinflammation. In addition, all subjects received a T1weighted MRI that was co-registered to the PET images. Parametric images, showing 15O-water CBF and 11CPK11195 binding potential (BPND) at the voxel level, were calculated. Mean total grey matter CBF and BPND values were calculated for all subjects. The co-registered MRI images were normalized to MNI standard space using statistical parametric mapping (SPM12) and the transformation matrices were applied to the respective parametric images. A voxel-wise z-test was performed in SPM12 to compare each 15Owater CBF and 11CPK11195 BPND image from the post COVID-19 patients to the HC CBF and BPND images, respectively. A statistical threshold of p<0.05 was applied. Result(s): Two of the subjects with remaining post COVID-19 symptoms demonstrated a significantly increased CBF in the whole brain compared to the HC. Total grey matter CBF values were 1.27 and 1.41 mL/cm3/min in these two subjects, compared to a mean +/- SD of 0.65 +/- 0.19 mL/cm3/min in the HC group. The subject with persisting headache also showed large clusters of significant increased 11C-PK11195 BPND in the meninges. Mean total grey matter 11CPK11195 BPND values in post COVID-19 subjects were within the range of values in the HC group. The other two subjects did not show increased CBF and no significant increase of 11C-PK11195 BPND. Conclusion(s): Neurological symptoms from post COVID-19 may be due to increased CBF and inflammation. However, further investigations are needed with larger study cohort to better understand the relation between post COVID-19 symptoms and neurological dysfunctions investigated with PET.

Donepezil Beyond Alzheimer’s Disease? A Narrative Review of Therapeutic Potentials of Donepezil in Different Diseases

Donepezil hydrochloride is an acetylcholine esterase inhibitor studied and approved to treat Alzheimer’s disease (AD). However, this drug can have positive therapeutic potential in treating different conditions, including various neurodegenerative disorders such as other types of dementia, multiple sclerosis, Parkinson’s disease, psychiatric and mood disorders, and even infectious diseases. Hence, this study reviewed the therapeutic potential of this drug in treating Alzheimer’s and other diseases by reviewing the articles from databases including Web of Science, Scopus, PubMed, Cochrane, and Science Direct. It was shown that donepezil could affect the pathophysiology of these diseases via mechanisms such as increasing the concentration of acetylcholine, modulating local and systemic inflammatory processes, affecting acetylcholine receptors like nicotinic and muscarinic receptors, and activating various cellular signaling via receptors like sigma-1 receptors. Despite many therapeutic potentials, this drug has not yet been approved for treating non-Alzheimer’s diseases, and more comprehensive studies are needed.