Inflammation-relevant microbiome signature of the stroke brain, gut, spleen, and thymus and the impact of exercise.

Stroke remains a significant unmet need in the clinic with few therapeutic options. We, and others, have implicated the role of inflammatory microbiota in stroke secondary cell death. Elucidating this inflammation microbiome as a biomarker may improve stroke diagnosis and treatment. Here, adult Sprague-Dawley rats performed 30 minutes of exercise on a motorized treadmill for 3 consecutive days prior to transient middle cerebral artery occlusion (MCAO). Stroke animals that underwent exercise showed 1) robust behavioral improvements, 2) significantly smaller infarct sizes and increased peri-infarct cell survival and 3) decreasing trends of inflammatory microbiota BAC303, EREC482, and LAB158 coupled with significantly reduced levels of inflammatory markers ionized calcium binding adaptor molecule 1, tumor necrosis factor alpha, and mouse monoclonal MHC Class II RT1B in the brain, gut, spleen, and thymus compared to non-exercised stroke rats. These results suggest that a specific set of inflammatory microbiota exists in central and peripheral organs and can serve as a disease biomarker and a therapeutic target for stroke.

Progress in progestin-based therapies for neurological disorders.

Hormone therapy, primarily progesterone and progestins, for central nervous system (CNS) disorders represents an emerging field of regenerative medicine. Following a failed clinical trial of progesterone for traumatic brain injury treatment, attention has shifted to the progestin Nestorone for its ability to potently and selectively transactivate progesterone receptors at relatively low doses, resulting in robust neurogenetic, remyelinating, and anti-inflammatory effects. That CNS disorders, including multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS), spinal cord injury (SCI), and stroke, develop via demyelinating, cell death, and/or inflammatory pathological pathways advances Nestorone as an auspicious candidate for these disorders. Here, we assess the scientific and clinical progress over decades of research into progesterone, progestins, and Nestorone as neuroprotective agents in MS, ALS, SCI, and stroke. We also offer recommendations for optimizing timing, dosage, and route of the drug regimen, and identifying candidate patient populations, in advancing Nestorone to the clinic.

Mesenchymal stem cell therapy alleviates the neuroinflammation associated with acquired brain injury.

Ischemic stroke and traumatic brain injury (TBI) comprise two particularly prevalent and costly examples of acquired brain injury (ABI). Following stroke or TBI, primary cell death and secondary cell death closely model disease progression and worsen outcomes. Mounting evidence indicates that long-term neuroinflammation extensively exacerbates the secondary deterioration of brain structure and function. Due to their immunomodulatory and regenerative properties, mesenchymal stem cell transplants have emerged as a promising approach to treating this facet of stroke and TBI pathology. In this review, we summarize the classification of cell death in ABI and discuss the prominent role of inflammation. We then consider the efficacy of bone marrow-derived mesenchymal stem/stromal cell (BM-MSC) transplantation as a therapy for these injuries. Finally, we examine recent laboratory and clinical studies utilizing transplanted BM-MSCs as antiinflammatory and neurorestorative treatments for stroke and TBI. Clinical trials of BM-MSC transplants for stroke and TBI support their promising protective and regenerative properties. Future research is needed to allow for better comparison among trials and to elaborate on the emerging area of cell-based combination treatments.

Enhanced survival of human-induced pluripotent stem cell transplant in parkinsonian rat brain by locally applied cyclosporine.

A major limitation with cell transplantation in patients is the unimpressive number of cells survived. The death of grafted cells involves apoptosis and immunorejection. In this review, we encapsulate the recent preclinical development that improves the survival of grafted cells and mitigates the immunorejection of human-induced pluripotent stem cells (iPSCs) through co-grating nanoparticles-containing cyclosporine A (NanoCsA) in hemiparkinsonian rats. The study supported the notion that NanoCsA allows for long-lasting CsA discharge and limits immunorejection of human iPSC xenograft in a 6-hydroxydopamine Parkinson's disease rat model.