Anti-CD49d Ab treatment ameliorates age-associated inflammatory response and mitigates CD8 T-cell cytotoxicity after traumatic brain injury.

Patients aged 65 years and older account for an increasing proportion of patients with traumatic brain injury (TBI). Older TBI patients experience increased morbidity and mortality compared to their younger counterparts. Our prior data demonstrated that by blocking α4 integrin, anti-CD49d antibody (aCD49d Ab) abrogates CD8 T-cell infiltration into the injured brain, improves survival, and attenuates neurocognitive deficits.

antiCD49d Ab treatment ameliorates age-associated inflammatory response and mitigates CD8+ T-cell cytotoxicity after traumatic brain injury.

Unlabelled: Patients aged 65 years and older account for an increasing proportion of patients with traumatic brain injury (TBI). Older TBI patients experience increased morbidity and mortality compared to their younger counterparts. Our prior data demonstrated that by blocking α4 integrin, anti-CD49d antibody (aCD49d Ab) abrogates CD8+ T-cell infiltration into the injured brain, improves survival, and attenuates neurocognitive deficits.

MICROGLIA AND INFILTRATING T-CELLS ADOPT LONG-TERM, AGE-SPECIFIC, TRANSCRIPTIONAL CHANGES AFTER TRAUMATIC BRAIN INJURY IN MICE.

Aged traumatic brain injury (TBI) patients suffer increased mortality and long-term neurocognitive and neuropsychiatric morbidity compared with younger patients. Microglia, the resident innate immune cells of the brain, are complicit in both. We hypothesized that aged microglia would fail to return to a homeostatic state after TBI and adopt a long-term injury-associated state within aged brains compared with young brains after TBI.

POSTINJURY FECAL MICROBIOME TRANSPLANT DECREASES LESION SIZE AND NEUROINFLAMMATION IN TRAUMATIC BRAIN INJURY.

Background: Traumatic brain injury (TBI) is an underrecognized public health threat. The constitutive activation of microglia after TBI has been linked to long-term neurocognitive deficits and the progression of neurodegenerative disease. Evolving evidence indicates a critical role for the gut-brain axis in this process.

Fecal Microbiota Transfer Attenuates Gut Dysbiosis and Functional Deficits After Traumatic Brain Injury.

Background: Traumatic brain injury (TBI) is an underrecognized public health threat. Survivors of TBI often suffer long-term neurocognitive deficits leading to the progressive onset of neurodegenerative disease. Recent data suggests that the gut-brain axis is complicit in this process.

Differential Fecal Microbiome Dysbiosis after Equivalent Traumatic Brain Injury in Aged Versus Young Adult Mice.

Traumatic brain injury (TBI) has a bimodal age distribution with peak incidence at age 24 and age 65 with worse outcomes developing in aged populations. Few studies have specifically addressed age at the time of injury as an independent biologic variable in TBI-associated secondary pathology. Within the framework of our published work, identifying age related effects of TBI on neuropathology, cognition, memory and motor function we analyzed fecal pellets collected from young and aged TBI animals to assess for age-induced effects in TBI induced dysbiosis.

APOE4-mediated Alzheimer disease and "Vascular"-"Meningeal Lymphatic" components: towards a novel therapeutic era?

A three-dimensional graphic design representation of the potential role of meningeal vessels in Alzheimer disease. Although there are major differences between APOE4(+) and APOE4(−) Alzheimer disease cases (described in detail in the Comment article by Mentis and colleagues), the figure depicts the clearance of macromolecules and other solutes from meningeal lymphatic vessels. Cover image: Ella Maru Studio.

Differential neuropathology and functional outcome after equivalent traumatic brain injury in aged versus young adult mice.

The CDC estimate that nearly 3 million Americans sustain a traumatic brain injury (TBI) each year. Even when medical comorbidities are accounted for, age is an independent risk factor for poor outcome after TBI. Nonetheless, few studies have examined the pathophysiology of age-linked biologic outcomes in TBI.

Microglia Adopt Longitudinal Transcriptional Changes After Traumatic Brain Injury.

Background: Traumatic brain injury (TBI) is an under-recognized public health threat. Even mild brain injuries can lead to long-term neurologic impairment. Microglia play a fundamental role in the development and progression of this ensuing neurologic impairment.

Murine Model of Controlled Cortical Impact for the Induction of Traumatic Brain Injury.

The Centers for Disease Control and Injury Prevention estimate that almost 2 million people sustain a traumatic brain injury (TBI) every year in the United States. In fact, TBI is a contributing factor to over a third of all injury-related mortality. Nonetheless, the cellular and molecular mechanisms underlying the pathophysiology of TBI are poorly understood.

Monocyte depletion attenuates the development of posttraumatic hydrocephalus and preserves white matter integrity after traumatic brain injury.

Monocytes are amongst the first cells recruited into the brain after traumatic brain injury (TBI). We have shown monocyte depletion 24 hours prior to TBI reduces brain edema, decreases neutrophil infiltration and improves behavioral outcomes. Additionally, both lesion and ventricle size correlate with poor neurologic outcome after TBI.

Spontaneous reduction of acute cecal herniation through the foramen of Winslow.

This is the case of a 70-year-old woman who presented to the emergency department complaining of 2 hours of acute-onset epigastric pain. She had experienced this pain once before which had spontaneously resolved. Axial imaging demonstrated the cecum in an abnormal position within the lesser sac, as well as compression of the inferior vena cava and portal vein.

Nonclassical Monocytes Mediate Secondary Injury, Neurocognitive Outcome, and Neutrophil Infiltration after Traumatic Brain Injury.

Traumatic brain injury (TBI) results in rapid recruitment of leukocytes into the injured brain. Monocytes constitute a significant proportion of the initial infiltrate and have the potential to propagate secondary brain injury or generate an environment of repair and regeneration. Monocytes are a diverse population of cells (classical, intermediate, and nonclassical) with distinct functions, however, the recruitment order of these subpopulations to the injured brain largely remains unknown.

The Role of Microglia in the Etiology and Evolution of Chronic Traumatic Encephalopathy.

Chronic traumatic encephalopathy (CTE) is a progressive neurodegenerative disease that presents as a late sequela from traumatic brain injury (TBI). TBI is a growing and under-recognized public health concern with a high degree of morbidity and large associated global costs. While the immune response to TBI is complex, its contribution to the development of CTE remains largely unknown.

Differential Activation of Infiltrating Monocyte-Derived Cells After Mild and Severe Traumatic Brain Injury.

Microglia are the resident innate immune cells of the brain. Although embryologically and functionally distinct, they are morphologically similar to peripheral monocyte-derived cells, resulting in a poor ability to discriminate between the two cell types. The purpose of this study was to develop a rapid and reliable method to simultaneously characterize, quantify, and discriminate between whole populations of myeloid cells from the brain in a murine model of traumatic brain injury.

Traumatic brain injury-induced alterations in peripheral immunity.

Background: The complex alterations that occur in peripheral immunity after traumatic brain injury (TBI) have been poorly characterized to date. The purpose of this study was to determine the temporal changes in the peripheral immune response after TBI in a murine model of closed head injury.

Methods: C57Bl/6 mice underwent closed head injury via a weight drop technique (n = 5) versus sham injury (n = 3) per time point.

Surgical prophylaxis and other complication avoidance care bundles.

Individual health care quality measures that have been shown to improve outcome can be combined together into what are called care bundles, with the expectation that this set of practices produces further improvements in outcome. Prevention of surgical site infection is the focus of several quality measures put forward by the Surgical Care Improvement Project; these can collectively be considered a bundle as well. Whether these process measures, which include several components related to the administration of antibiotic prophylaxis, are effective in decreasing rates of surgical site infection has come under considerable debate recently.