PET imaging of microglia using PBR28suv determines therapeutic efficacy of autologous bone marrow mononuclear cells therapy in traumatic brain injury.

Traumatic brain injury (TBI) results in activated microglia. Activated microglia can be measured in vivo by using positron emission topography (PET) ligand peripheral benzodiazepine receptor standardized uptake values (PBR28suv). Cell based therapies have utilized autologous bone marrow mononuclear cells (BMMNCs) to attenuate activated microglia after TBI.

Microglia as therapeutic targets after neurological injury: strategy for cell therapy.

Introduction: Microglia is the resident tissue macrophages of the central nervous system. Prolonged microglial activation often occurs after traumatic brain injury and is associated with deteriorating neurocognitive outcomes. Resolution of microglial activation is associated with limited tissue loss and improved neurocognitive outcomes.

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).

Spatiotemporal Distribution of Microglia After Traumatic Brain Injury in Male Mice.

Traumatic brain injury (TBI) disrupts the complex arrangement of glia and neuronal cells in the central nervous system. Microglia, the resident immune cells, survey the cellular milieu under homeostatic conditions and play a neuroprotective role via clearance of dead cells and debris such as axons and myelin. Resting (ramified) microglia possess a distinct morphology—small rod-shaped somata with thin processes.

Human umbilical cord blood cells restore vascular integrity in injured rat brain and modulate inflammation .

Traumatic brain injury is a complex condition consisting of a mechanical injury with neurovascular disruption and inflammation with limited clinical interventions available. A growing number of studies report systemic delivery of human umbilical cord blood (HUCB) as a therapy for neural injuries. HUCB cells from five donors were tested to improve blood-brain barrier integrity in a traumatic brain injury rat model at a dose of 2.

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.

Do microglia play a role in sex differences in TBI?

Traumatic brain injury (TBI) is one of the leading causes of morbidity and mortality for both males and females and is, thus, a major focus of current study. Although the overall death rate of TBI for males is roughly three times higher than that for females, males have been disproportionately represented in clinical and preclinical studies. Gender differences are known to exist in many neurologic disorders, such as multiple sclerosis and stroke, and differences appear to exist in TBI.

Intravenous multipotent adult progenitor cell therapy attenuates activated microglial/macrophage response and improves spatial learning after traumatic brain injury.

We previously demonstrated that the intravenous delivery of multipotent adult progenitor cells (MAPCs) after traumatic brain injury (TBI) in rodents provides neuroprotection by preserving the blood-brain barrier and systemically attenuating inflammation in the acute time frame following cell treatment; however, the long-term behavioral and anti-inflammatory effects of MAPC administration after TBI have yet to be explored. We hypothesized that the intravenous injection of MAPCs after TBI attenuates the inflammatory response (as measured by microglial morphology) and improves performance at motor tasks and spatial learning (Morris water maze [MWM]). MAPCs were administered intravenously 2 and 24 hours after a cortical contusion injury (CCI).

Autologous bone marrow mononuclear cells therapy attenuates activated microglial/macrophage response and improves spatial learning after traumatic brain injury.

Background: Autologous bone marrow-derived mononuclear cells (AMNCs) have shown therapeutic promise for central nervous system insults such as stroke and traumatic brain injury (TBI). We hypothesized that intravenous injection of AMNC provides neuroprotection, which leads to cognitive improvement after TBI.

Methods: A controlled cortical impact (CCI) rodent TBI model was used to examine blood-brain barrier (BBB) permeability, neuronal and glial apoptosis, as well as cognitive behavior.

Immunomagnetic enrichment and flow cytometric characterization of mouse microglia.

Background: The inflammatory response after a CNS injury is regulated by microglia/macrophages. Changes in the ratio of M1 classically activated pro-inflammatory cells versus M2 alternatively activated anti-inflammatory cells reveal the direction of the immune response. These cells are routinely identified and enumerated by morphology and cell-surface markers using immunohistochemistry.

Intravenous multipotent adult progenitor cell therapy after traumatic brain injury: modulation of the resident microglia population.

Introduction: We have demonstrated previously that the intravenous delivery of multipotent adult progenitor cells (MAPC) after traumatic brain injury affords neuroprotection via interaction with splenocytes, leading to an increase in systemic anti-inflammatory cytokines. We hypothesize that the observed modulation of the systemic inflammatory milieu is related to T regulatory cells and a subsequent increase in the locoregional neuroprotective M2 macrophage population.

Methods: C57B6 mice were injected with intravenous MAPC 2 and 24 hours after controlled cortical impact injury.

Progenitor cells: therapeutic targets after traumatic brain injury.

Traumatic brain injuries and their associated treatments carry high cost in both financial impact and morbidity to human life. Recent studies and trials present promising results in reducing secondary injury in the days and weeks following the primary insult. A number of studies, both pre-clinical and clinical, have found that different populations of stem/progenitor cells result in a reduction of inflammation, maintenance of the blood brain barrier, and an overall improved prognosis.

Spinal cord injury triggers an intrinsic growth-promoting state in nociceptors.

Although most investigations of the mechanisms underlying chronic pain after spinal cord injury (SCI) have examined the central nervous system (CNS), recent studies have shown that nociceptive primary afferent neurons display persistent hyperexcitability and spontaneous activity in their peripheral branches and somata in dorsal root ganglia (DRG) after SCI. This suggests that SCI-induced alterations of primary nociceptors contribute to central sensitization and chronic pain after SCI. Does SCI also promote growth of these neurons' fibers, as has been suggested in some reports? The present study tests the hypothesis that SCI induces an intrinsic growth-promoting state in DRG neurons.

Chronic spontaneous activity generated in the somata of primary nociceptors is associated with pain-related behavior after spinal cord injury.

Mechanisms underlying chronic pain that develops after spinal cord injury (SCI) are incompletely understood. Most research on SCI pain mechanisms has focused on neuronal alterations within pain pathways at spinal and supraspinal levels associated with inflammation and glial activation. These events might also impact central processes of primary sensory neurons, triggering in nociceptors a hyperexcitable state and spontaneous activity (SA) that drive behavioral hypersensitivity and pain.

Effects of axotomy on cultured sensory neurons of Aplysia: long-term injury-induced changes in excitability and morphology are mediated by different signaling pathways.

To facilitate an understanding of injury-induced changes within the nervous system, we used a single-cell, in vitro model of axonal injury. Sensory neurons were individually dissociated from the CNS of Aplysia and placed into cell culture. The major neurite of some neurons was then transected (axotomized neurons).