Brain Region-Specific Histopathological Effects of Varying Trajectories of Controlled Cortical Impact Injury Model of Traumatic Brain Injury.

Aims: Traumatic brain injury (TBI) occurs when the head is impacted by an external force causing either a closed or penetrating head injury through a direct or accelerating impact. In laboratory research, most of the TBI animal models focus on a specific region to cause brain injury, but traumatic injuries in patients do not always impact the same brain regions. The aim of this study was to examine the histopathological effects of different angles of mechanical injury by manipulating the trajectory of the controlled cortical impact injury (CCI) model in adult Sprague-Dawley rats.

Gender-linked stem cell alterations in stroke and postpartum depression.

Stroke is a significant unmet clinical need. The current stroke treatment of tissue plasminogen activator is limited to the very acute 4.5 h after disease onset which benefits only less than 3% of ischemic stroke patients.

An Update on Translating Stem Cell Therapy for Stroke from Bench to Bedside.

With a constellation of stem cell sources available, researchers hope to utilize their potential for cellular repair as a therapeutic target for disease. However, many lab-to-clinic translational considerations must be given in determining their efficacy, variables such as the host response, effects on native tissue, and potential for generating tumors. This review will discuss the current knowledge of stem cell research in neurological disease, mainly stroke, with a focus on the benefits, limitations, and clinical potential.

Adult stem cell transplantation: is gender a factor in stemness?

Cell therapy now constitutes an important area of regenerative medicine. The aging of the population has mandated the discovery and development of new and innovative therapeutic modalities to combat devastating disorders such as stroke. Menstrual blood and Sertoli cells represent two sources of viable transplantable cells that are gender-specific, both of which appear to have potential as donor cells for transplantation in stroke.

Therapeutic outcomes of transplantation of amniotic fluid-derived stem cells in experimental ischemic stroke.

Accumulating preclinical evidence suggests the use of amnion as a source of stem cells for investigations of basic science concepts related to developmental cell biology, but also for stem cells' therapeutic applications in treating human disorders. We previously reported isolation of viable rat amniotic fluid-derived stem (AFS) cells. Subsequently, we recently reported the therapeutic benefits of intravenous transplantation of AFS cells in a rodent model of ischemic stroke.

Stem cell therapy for neonatal hypoxic-ischemic encephalopathy.

Treatments for neonatal hypoxic-ischemic encephalopathy (HIE) have been limited. The aim of this paper is to offer translational research guidance on stem cell therapy for neonatal HIE by examining clinically relevant animal models, practical stem cell sources, safety and efficacy of endpoint assays, as well as a general understanding of modes of action of this cellular therapy. In order to do so, we discuss the clinical manifestations of HIE, highlighting its overlapping pathologies with stroke and providing insights on the potential of cell therapy currently investigated in stroke, for HIE.

Stem cell-paved biobridge facilitates neural repair in traumatic brain injury.

Modified mesenchymal stromal cells (MSCs) display a unique mechanism of action during the repair phase of traumatic brain injury by exhibiting the ability to build a biobridge between the neurogenic niche and the site of injury. Immunohistochemistry and laser capture assay have visualized this biobridge in the area between the neurogenic subventricular zone and the injured cortex. This biobridge expresses high levels of extracellular matrix metalloproteinases (MMPs), which are initially co-localized with a stream of transplanted MSCs, but later this region contains only few to non-detectable grafts and becomes overgrown by newly recruited host cells.

Oligodendrocytes engineered with migratory proteins as effective graft source for cell transplantation in multiple sclerosis.

Multiple sclerosis (MS) is characterized by widespread immunomodulatory demyelination of the CNS resulting in nerve cell dysfunction. Accordingly, treatment strategies have been centered on immunodulation and remyelination, with the former primarily focused on reducing the pathology rather than enhancing myelin repair which the latter targets. While conceding to the emerging view of heterogeneity in the pathology of MS, which precludes variations in degree of immune response (i.

ESTROGEN REPLACEMENT THERAPY FOR STROKE.

Stroke is the third most common cause of death and severe disability among Western populations. Overall, the incidence of stroke is uniformly higher in men than in women. Stroke is rare in women during the reproductive years, and rapidly increases after menopause, strongly suggesting that estrogen (E2) plays an important role in the prevention of stroke.

Intravenous transplants of human adipose-derived stem cell protect the brain from traumatic brain injury-induced neurodegeneration and motor and cognitive impairments: cell graft biodistribution and soluble factors in young and aged rats.

Traumatic brain injury (TBI) survivors exhibit motor and cognitive symptoms from the primary injury that can become aggravated over time because of secondary cell death. In the present in vivo study, we examined the beneficial effects of human adipose-derived stem cells (hADSCs) in a controlled cortical impact model of mild TBI using young (6 months) and aged (20 months) F344 rats. Animals were transplanted intravenously with 4 × 10(6) hADSCs (Tx), conditioned media (CM), or vehicle (unconditioned media) at 3 h after TBI.

Advancing critical care medicine with stem cell therapy and hypothermia for cerebral palsy.

With limited clinical trials on stem cell therapy for adult stroke underway, the assessment of efficacy also needs to be considered for neonatal hypoxic-ischemic brain injury, considering its distinct symptoms. The critical nature of this condition leads to establishment of deficits that last a lifetime. Here, we will highlight the progress of current translational research, commenting on the critical nature of the disease, stem cell sources, the use of hypothermia, safety and efficacy of each treatment, modes of action, and the possibility of combination therapy.

Stem Cells for Neurovascular Repair in Stroke.

Stem cells exert therapeutic effects against ischemic stroke via transplantation of exogenous stem cells or stimulation of endogenous stem cells within the neurogenic niches of subventricular zone and subgranular zone, or recruited from the bone marrow through peripheral circulation. In this paper, we review the different sources of stem cells that have been tested in animal models of stroke. In addition, we discuss specific mechanisms of action, in particular neurovascular repair by endothelial progenitor cells, as key translational research for advancing the clinical applications of stem cells for ischemic stroke.

Delta opioid receptor and its peptide: a receptor-ligand neuroprotection.

In pursuit of neurological therapies, the opioid system, specifically delta opioid receptors and delta opioid peptides, demonstrates promising therapeutic potential for stroke, Parkinson's disease, and other degenerative neurological conditions. Recent studies offer strong evidence in support of the therapeutic use of delta opioid receptors, and provide insights into the underlying mechanisms of action. Delta opioid receptors have been shown to confer protective effects by mediating ionic homeostasis and activating endogenous neuroprotective pathways.

Blood-brain barrier alterations provide evidence of subacute diaschisis in an ischemic stroke rat model.

Background: Comprehensive stroke studies reveal diaschisis, a loss of function due to pathological deficits in brain areas remote from initial ischemic lesion. However, blood-brain barrier (BBB) competence in subacute diaschisis is uncertain. The present study investigated subacute diaschisis in a focal ischemic stroke rat model.

ADVANCES IN THE CELL-BASED TREATMENT OF NEONATAL HYPOXIC-ISCHEMIC BRAIN INJURY.

Stem cell therapy for adult stroke has reached limited clinical trials. Here, we provide translational research guidance on stem cell therapy for neonatal hypoxic-ischemic brain injury requiring a careful consideration of clinically relevant animal models, feasible stem cell sources, and validated safety and efficacy endpoint assays, as well as a general understanding of modes of action of this cellular therapy. To this end, we refer to existing translational guidelines, in particular the recommendations outlined in the consortium of academicians, industry partners and regulators called Stem cell Therapeutics as an Emerging Paradigm for Stroke or STEPS.

A spirulina-enhanced diet provides neuroprotection in an α-synuclein model of Parkinson's disease.

Inflammation in the brain plays a major role in neurodegenerative diseases. In particular, microglial cell activation is believed to be associated with the pathogenesis of neurodegenerative diseases, including Parkinson's disease (PD). An increase in microglia activation has been shown in the substantia nigra pars compacta (SNpc) of PD models when there has been a decrease in tyrosine hydroxylase (TH) positive cells.

CX3CL1 reduces neurotoxicity and microglial activation in a rat model of Parkinson's disease.

Background: Parkinson's disease is characterized by a progressive loss of dopaminergic neurons in the substantia nigra. The cause of the neurodegeneration is unknown. Neuroinflammation has been clearly shown in Parkinson's disease and may be involved in the progressive nature of the disease.

Peripheral injection of human umbilical cord blood stimulates neurogenesis in the aged rat brain.

Background: Neurogenesis continues to occur throughout life but dramatically decreases with increasing age. This decrease is mostly related to a decline in proliferative activity as a result of an impoverishment of the microenvironment of the aged brain, including a reduction in trophic factors and increased inflammation.

Results: We determined that human umbilical cord blood mononuclear cells (UCBMC) given peripherally, by an intravenous injection, could rejuvenate the proliferative activity of the aged neural stem/progenitor cells.