Administration of low intensity vibration and a RANKL inhibitor, alone or in combination, reduces bone loss after spinal cord injury-induced immobilization in rats.

We previously reported an ability of low-intensity vibration (LIV) to improve selected biomarkers of bone turnover and gene expression and reduce osteoclastogenesis but lacking of evident bone accrual. In this study, we demonstrate that a prolonged course of LIV that initiated at 2 weeks post-injury and continued for 8 weeks can protect against bone loss after SCI in rats. LIV stimulates bone formation and improves osteoblast differentiation potential of bone marrow stromal stem cells while inhibiting osteoclast differentiation potential of marrow hematopoietic progenitors to reduce bone resorption.

Beneficial Effects of Human Schwann Cell-Derived Exosomes in Mitigating Secondary Damage After Penetrating Ballistic-Like Brain Injury.

There is a growing body of evidence that the delivery of cell-derived exosomes normally involved in intracellular communication can reduce secondary injury mechanisms after brain and spinal cord injury and improve outcomes. Exosomes are nanometer-sized vesicles that are released by Schwann cells and may have neuroprotective effects by reducing post-traumatic inflammatory processes as well as promoting tissue healing and functional recovery. The purpose of this study was to evaluate the beneficial effects of human Schwann-cell exosomes (hSC-Exos) in a severe model of penetrating ballistic-like brain injury (PBBI) in rats and investigate effects on multiple outcomes.

Association of region-specific hippocampal reduction of neurogranin with inflammasome proteins in brains of Alzheimer's disease.

Introduction: Neurogranin (Ng) is considered a biomarker for synaptic dysfunction in Alzheimer's disease (AD). In contrast, the inflammasome complex has been shown to exacerbate AD pathology.

Methods: We investigated the protein expression, morphological differences of Ng, and correlated Ng to hyperphosphorylated tau in the brains of 17 AD cases and 17 age- and sex-matched controls.

Electronic Cigarette Vape Exposure Exacerbates Post-Ischemic Outcomes in Female but Not in Male Rats.

Background: Nicotine-containing electronic cigarette (EC) vaping has become popular worldwide, and our understanding of the effects of vaping on stroke outcomes is elusive. Using a rat model of transient middle cerebral artery occlusion, the current exploratory study aims to evaluate the sex-dependent effects of EC exposure on brain energy metabolism and stroke outcomes.

Methods: Adult Sprague-Dawley rats of both sexes were randomly assigned to air/EC vapor (5% nicotine Juul pods) exposure for 16 nights, followed by randomization into 3 cohorts.

A Perspective on Hormonal Contraception Usage in Central Nervous System Injury.

Naturally occurring life stages in women are associated with changes in the milieu of endogenous ovarian hormones. Women of childbearing age may be exposed to exogenous ovarian hormone(s) because of their use of varying combinations of estrogen and progesterone hormones-containing oral contraceptives (OC; also known as "the pill"). If women have central nervous system (CNS) injury such as spinal cord injury (SCI) and traumatic brain injury (TBI) during their childbearing age, they are likely to retain their reproductive capabilities and may use OC.

Multimodal magnetic resonance imaging after experimental moderate and severe traumatic brain injury: A longitudinal correlative assessment of structural and cerebral blood flow changes.

Traumatic brain injury (TBI) is a worldwide problem that results in death or disability for millions of people every year. Progressive neurological complications and long-term impairment can significantly disrupt quality of life. We demonstrated the feasibility of multiple magnetic resonance imaging (MRI) modalities to investigate and predict aberrant changes and progressive atrophy of gray and white matter tissue at several acute and chronic time points after moderate and severe parasagittal fluid percussion TBI.

Association between Cerebrospinal Fluid and Serum Biomarker Levels and Diagnosis, Injury Severity, and Short-Term Outcomes in Patients with Acute Traumatic Spinal Cord Injury.

Acute traumatic spinal cord injury (SCI) is recognized as a global problem that can lead to a range of acute and secondary complications impacting morbidity and mortality. There is still a lack of reliable diagnostic and prognostic biomarkers in patients with SCI that could help guide clinical care and identify novel therapeutic targets for future drug discovery. The aim of this prospective controlled study was to determine the cerebral spinal fluid (CSF) and serum profiles of 10 biomarkers as indicators of SCI diagnosis, severity, and prognosis to aid in assessing appropriate treatment modalities.

Dose-dependent modulation of microglia activation in rats after penetrating traumatic brain injury (pTBI) by transplanted human neural stem cells.

Traumatic brain injury (TBI) often results in long-lasting patterns of neurological deficits including motor, sensory, and cognitive abnormalities. Cranial gunshot survivors are among the most disabled TBI patients and face a lifetime of disability with no approved strategies to protect or repair the brain after injury. Recent studies using a model of penetrating TBI (pTBI) have reported that human neural stem cells (hNSCs) transplantation can lead to dose and location-dependent neuroprotection.

Post-stroke periodic estrogen receptor-beta agonist improves cognition in aged female rats.

Women have a higher risk of having an ischemic stroke and increased cognitive decline after stroke as compared to men. The female sex hormone 17β-estradiol (E2) is a potent neuro- and cognitive-protective agent. Periodic E2 or estrogen receptor subtype-beta (ER-β) agonist pre-treatments every 48 h before an ischemic episode ameliorated ischemic brain damage in young ovariectomized or reproductively senescent (RS) aged female rats.

Identification of inflammasome signaling proteins in neurons and microglia in early and intermediate stages of Alzheimer's disease.

Alzheimer's disease (AD) is a progressive neurodegenerative disease that destroys memory and cognitive function. Inflammasome activation has been suggested to play a critical role in the neuroinflammatory response in AD progression, but the cell-type expression of inflammasome proteins in the brain has not been fully characterized. In this study, we used samples from the hippocampus formation, the subiculum, and the entorhinal cortex brain from 17 donors with low-level AD pathology and 17 intermediate AD donors to assess the expression of inflammasome proteins.

Inflammasome activation in traumatic brain injury and Alzheimer's disease.

Traumatic brain injury (TBI) and Alzheimer's disease (AD) represent 2 of the largest sources of death and disability in the United States. Recent studies have identified TBI as a potential risk factor for AD development, and numerous reports have shown that TBI is linked with AD associated protein expression during the acute phase of injury, suggesting an interplay between the 2 pathologies. The inflammasome is a multi-protein complex that plays a role in both TBI and AD pathologies, and is characterized by inflammatory cytokine release and pyroptotic cell death.

Inflammasome-Regulated Pyroptotic Cell Death in Disruption of the Gut-Brain Axis After Stroke.

Approximately 50% of stroke survivors experience gastrointestinal complications. The innate immune response plays a role in changes to the gut-brain axis after stroke. The purpose of this study is to examine the importance of inflammasome-mediated pyroptosis in disruption of the gut-brain axis after experimental stroke.

Traumatic brain injury in women across lifespan.

Traumatic brain injury (TBI) is a leading cause of death and disability and a global public health challenge. Every year more than 50 million people suffer a TBI, and it is estimated that 50% of the global population will experience at least one TBI in their lifetime. TBI affects both men and women of all ages, however there is a male bias in TBI research as women have frequently been left out of the literature despite irrefutable evidence of male and female dimorphism in several posttraumatic measures.

Irisin-Associated Neuroprotective and Rehabilitative Strategies for Stroke.

Irisin, a newly discovered protein hormone that is secreted in response to low frequency whole body vibration (LFV), could be a promising post-stroke rehabilitation therapy for patients who are frail and cannot comply with regular rehabilitation therapy. Irisin is generated from a membrane-bound precursor protein fibronectin type III domain-containing protein 5 (FNDC5). Aside from being highly expressed in muscle, FNDC5 is highly expressed in the brain.

Kollidon VA64 Treatment in Traumatic Brain Injury: Operation Brain Trauma Therapy.

Loss of plasmalemmal integrity may mediate cell death after traumatic brain injury (TBI). Prior studies in controlled cortical impact (CCI) indicated that the membrane resealing agent Kollidon VA64 improved histopathological and functional outcomes. Kollidon VA64 was therefore selected as the seventh therapy tested by the Operation Brain Trauma Therapy consortium, across three pre-clinical TBI rat models: parasagittal fluid percussion injury (FPI), CCI, and penetrating ballistic-like brain injury (PBBI).

Glibenclamide Treatment in Traumatic Brain Injury: Operation Brain Trauma Therapy.

Glibenclamide (GLY) is the sixth drug tested by the Operation Brain Trauma Therapy (OBTT) consortium based on substantial pre-clinical evidence of benefit in traumatic brain injury (TBI). Adult Sprague-Dawley rats underwent fluid percussion injury (FPI;  = 45), controlled cortical impact (CCI;  = 30), or penetrating ballistic-like brain injury (PBBI;  = 36). Efficacy of GLY treatment (10-μg/kg intraperitoneal loading dose at 10 min post-injury, followed by a continuous 7-day subcutaneous infusion [0.