Autologous bone marrow mononuclear cells to treat severe traumatic brain injury in children.

Autologous bone marrow mononuclear cells (BMMNCs) infused after severe traumatic brain injury have shown promise for treating the injury. We evaluated their impact in children, particularly their hypothesized ability to preserve the blood-brain barrier and diminish neuroinflammation, leading to structural CNS preservation with improved outcomes. We performed a randomized, double-blind, placebo-sham-controlled Bayesian dose-escalation clinical trial at two children's hospitals in Houston, TX and Phoenix, AZ, USA (NCT01851083).

Autologous cellular therapy for cerebral palsy: a randomized, crossover trial.

We examined an autologous mononuclear-cell-therapy-based approach to treat cerebral palsy using autologous umbilical cord blood or bone-marrow-derived mononuclear cells. The primary objective was to determine if autologous cells are safe to administer in children with cerebral palsy. The secondary objectives were to determine if there was improvement in motor function of patients 12 months after infusion using the Gross Motor Function Measure and to evaluate impact of treatment on corticospinal tract microstructure as determined by radial diffusivity measurement.

PET Imaging of Peripheral Benzodiazepine Receptor Standard Uptake Value Increases After Controlled Cortical Impact, a Rodent Model of Traumatic Brain Injury.

Traumatic brain injury (TBI) is a chronic, life threatening injury for which few effective interventions are available. Evidence in animal models suggests un-checked immune activation may contribute to the pathophysiology. Changes in regional density of active brain microglia can be quantified in vivo with positron emission topography (PET) with the relatively selective radiotracer, peripheral benzodiazepine receptor 28 (11 C-PBR28).

Lack of Racial, Ethnic, and Sex Disparities in Ischemic Stroke Care Metrics within a Tele-Stroke Network.

Introduction: Differences in access to stroke care and compliance with standard of care stroke management among patients of varying racial and ethnic backgrounds and sex are well-characterized. However, little is known on the impact of telestroke in addressing disparities in acute ischemic stroke care.

Methods: We conducted a retrospective review of acute ischemic stroke patients evaluated over our 17-hospital telestroke network in Texas from 2015-2018.

Call to Action: SARS-CoV-2 and CerebrovAscular DisordErs (CASCADE).

Background And Purpose: The novel severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2), now named coronavirus disease 2019 (COVID-19), may change the risk of stroke through an enhanced systemic inflammatory response, hypercoagulable state, and endothelial damage in the cerebrovascular system. Moreover, due to the current pandemic, some countries have prioritized health resources towards COVID-19 management, making it more challenging to appropriately care for other potentially disabling and fatal diseases such as stroke. The aim of this study is to identify and describe changes in stroke epidemiological trends before, during, and after the COVID-19 pandemic.

Clinical parameters affecting multipotent adult progenitor cells .

Background: Human multipotent adult progenitor cells (MAPC®) are an emerging therapy for traumatic brain injury (TBI); however, clinically translating a therapy involves overcoming many factors which are not present in pre-clinical testing. In this study we examined clinical parameters that may impact cell therapy efficacy.

Methods: MAPC were infused through varying gauged needles and catheters with and without chlorhexidine, and their viability tested with trypan blue exclusion.

Pre-injury monocyte/macrophage depletion results in increased blood-brain barrier permeability after traumatic brain injury.

Traumatic brain injury (TBI) effects both the brain and the immune system. Circulating monocytes/macrophages (M /M ) after a TBI may play an important role in preserving the blood-brain barrier (BBB), reducing brain edema, and interacting with resident microglia. To elucidate the role of circulating M /M , we utilized a monocyte/macrophage depletion model in response to TBI in male rats.

Therapeutic time window of multipotent adult progenitor therapy after traumatic brain injury.

Background: Traumatic brain injury (TBI) is a major cause of death and disability. TBI results in a prolonged secondary central neuro-inflammatory response. Previously, we have demonstrated that multiple doses (2 and 24 h after TBI) of multipotent adult progenitor cells (MAPC) delivered intravenously preserve the blood-brain barrier (BBB), improve spatial learning, and decrease activated microglia/macrophages in the dentate gyrus of the hippocampus.

Biomechanical Forces Promote Immune Regulatory Function of Bone Marrow Mesenchymal Stromal Cells.

Mesenchymal stromal cells (MSCs) are believed to mobilize from the bone marrow in response to inflammation and injury, yet the effects of egress into the vasculature on MSC function are largely unknown. Here we show that wall shear stress (WSS) typical of fluid frictional forces present on the vascular lumen stimulates antioxidant and anti-inflammatory mediators, as well as chemokines capable of immune cell recruitment. WSS specifically promotes signaling through NFκB-COX2-prostaglandin E (PGE ) to suppress tumor necrosis factor-α (TNF-α) production by activated immune cells.

Treatment of Severe Adult Traumatic Brain Injury Using Bone Marrow Mononuclear Cells.

Preclinical studies using bone marrow derived cells to treat traumatic brain injury have demonstrated efficacy in terms of blood-brain barrier preservation, neurogenesis, and functional outcomes. Phase 1 clinical trials using bone marrow mononuclear cells infused intravenously in children with severe traumatic brain injury demonstrated safety and potentially a central nervous system structural preservation treatment effect. This study sought to confirm the safety, logistic feasibility, and potential treatment effect size of structural preservation/inflammatory biomarker mitigation in adults to guide Phase 2 clinical trial design.

Pharmacological postconditioning with lactic acid and hydrogen rich saline alleviates myocardial reperfusion injury in rats.

This study investigated whether pharmacological postconditioning with lactic acid and hydrogen rich saline can provide benefits similar to that of mechanical postconditioning. To our knowledge, this is the first therapeutic study to investigate the co-administration of lactic acid and hydrogen. SD rats were randomly divided into 6 groups: Sham, R/I, M-Post, Lac, Hyd, and Lac + Hyd.

Strategies for CNS repair following TBI.

Traumatic brain injury (TBI) imparts a significant health burden in the United States, leaving many patients with chronic deficits. Improvement in clinical outcome following TBI has been hindered by a lack of treatments that have proven successful during phase III trials. Research remains active into a variety of non-pharmacologic, small molecule, endocrine and cell based therapies.