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Acute cerebral ischemia triggers a profound inflammatory response. While macrophages polarized to an M2-like phenotype clear debris and facilitate tissue repair, aberrant or prolonged macrophage activation is counterproductive to recovery. The inhibitory immune checkpoint Programmed Cell Death Protein 1 (PD-1) is upregulated on macrophage precursors (monocytes) in the blood after acute cerebrovascular injury. To investigate the therapeutic potential of PD-1 activation, we immunophenotyped circulating monocytes from patients and found that PD-1 expression was upregulated in the acute period after stroke. Murine studies using a temporary middle cerebral artery (MCA) occlusion (MCAO) model showed that intraperitoneal administration of soluble Programmed Death Ligand-1 (sPD-L1) significantly decreased brain edema and improved overall survival. Mice receiving sPD-L1 also had higher performance scores short-term, and more closely resembled sham animals on assessments of long-term functional recovery. These clinical and radiographic benefits were abrogated in global and myeloid-specific PD-1 knockout animals, confirming PD-1+ monocytes as the therapeutic target of sPD-L1. Single-cell RNA sequencing revealed that treatment skewed monocyte maturation to a non-classical Ly6C lo , CD43 hi , PD-L1+ phenotype. These data support peripheral activation of PD-1 on inflammatory monocytes as a therapeutic strategy to treat neuroinflammation after acute ischemic stroke., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: HB has received research funding from the National Institutes of Health, Khatib Foundation, NICO Myriad Corporation, and philanthropy. He is the Chairman of the Medical Advisory Board for Insightec, which is developing focused ultrasound treatments for brain tumors. This arrangement has been reviewed and approved by Johns Hopkins University in accordance with its conflict-of-interest policies. He has consultation agreements with Accelerating Combination Therapies, Insightec, Candel Therapeutics, Inc., Catalio Nexus Fund II, LLC, LikeMinds, Inc*, Galen Robotics, Inc.*, CraniUS*, and Nurami Medical* (Includes equity or options). ML has received research funding from Arbor, Bristol Myers Squibb, Accuray, Biohaven, and Urogen. He is a consultant for VBI, InCephalo Therapeutics, Merck, Pyramid Bio, Insightec, Biohaven. Sanianoia, Novocure, Noxxon, Hemispherian, InCando, Century Therapeutics, CraniUs, MediFlix, and XSense. He is a shareholder in Egret Therapeutics. He is an inventor on patents for focused radiation + checkpoint inhibitors, local chemotherapy + checkpoint inhibitors, and checkpoints and Neuro-inflammation. He is a non-research consultant for Stryker and on the DSMB for Cellularity. RJT is an inventor on patents for immune checkpoints and neuroinflammation. CMJ has received research support from Biohaven, InCephalo, the Goldhirsh-Yellin Foundation, the Brain Aneurysm Foundation, and philanthropy. He is an inventor on patents for immune checkpoints and neuroinflammation. He is the co-founder and owns equity interest in Egret Therapeutics. This arrangement has been reviewed and approved by Johns Hopkins University in accordance with its conflict-of-interest policies., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Spontaneous intracerebral hematoma (ICH) is a common disease with a dismal overall prognosis. Recent development of minimally invasive ICH evacuation techniques has shown promising results. Commercially available tubular retractors are commonly used for minimally invasive ICH evacuation yet are globally unavailable., Methods: A novel U.S. $7 cost-effective, off-the-shelf, atraumatic tubular retractor for minimally invasive intracranial surgery is described. Patients with acute spontaneous ICH underwent microsurgical tubular retractor-assisted minimally invasive ICH evacuation using the novel retractor. Patient outcome was retrospectively analyzed and compared with open surgery and with commercial tubular retractors., Results: Ten adult patients with spontaneous supratentorial ICH and median preoperative Glasgow Coma Scale score of 10 were included. ICH involved the frontal lobe, parietal lobe, occipitotemporal region, and solely basal ganglia in 3, 3, 2, and 2 patients, respectively. Mean preoperative ICH volume was 80 mL. Mean residual hematoma volume was 8.7 mL and mean volumetric hematoma reduction was 91% (median, 94%). Seven patients (70%) underwent >90% volumetric hematoma reduction. The total median length of hospitalization was 26 days. On discharge, the median Glasgow Coma Scale score was 12.5 (mean, 11.7). Thirty to 90 days' follow-up data were available for 9 patients (90%). The mean follow-up modified Rankin Scale score was 3.7 and 5 patients (56%) had a modified Rankin Scale score of 3., Conclusions: The novel cost-effective tubular retractor and microsurgical technique offer a safe and effective method for minimally invasive ICH evacuation. Cost-effective tubular retractors may continue to present a valid alternative to commercial tubular retractors., (Copyright © 2021 Elsevier Inc. All rights reserved.)