Exosomes derived from umbilical cord mesenchymal stem cells reduce microglia-mediated neuroinflammation in perinatal brain injury.

BACKGROUND: Preterm newborns are at high risk of developing neurodevelopmental deficits caused by neuroinflammation leading to perinatal brain injury. Human Wharton's jelly mesenchymal stem cells (hWJ-MSC) derived from the umbilical cord have been suggested to reduce neuroinflammation, in part through the release of extracellular vesicle-like exosomes. Here, we studied whether exosomes derived from hWJ-MSC have anti-inflammatory effects on microglia-mediated neuroinflammation in perinatal brain injury. METHODS: Using ultracentrifugation, we isolated exosomes from hWJ-MSC culture supernatants. In an in vitro model of neuroinflammation, we stimulated immortalized BV-2 microglia and primary mixed glial cells with lipopolysaccharide (LPS) in the presence or absence of exosomes. In vivo, we introduced brain damage in 3-day-old rat pups and treated them intranasally with hWJ-MSC-derived exosomes. RESULTS: hWJ-MSC-derived exosomes dampened the LPS-induced expression of inflammation-related genes by BV-2 microglia and primary mixed glial cells. The secretion of pro-inflammatory cytokines by LPS-stimulated primary mixed glial was inhibited by exosomes as well. Exosomes interfered within the Toll-like receptor 4 signaling of BV-2 microglia, as they prevented the degradation of the NFκB inhibitor IκBα and the phosphorylation of molecules of the mitogen-activated protein kinase family in response to LPS stimulation. Finally, intranasally administered exosomes reached the brain and reduced microglia-mediated neuroinflammation in rats with perinatal brain injury. CONCLUSIONS: Our data suggest that the administration of hWJ-MSC-derived exosomes represents a promising therapy to prevent and treat perinatal brain injury.

[HEAD INJURY DURING PREGNANCY].

No matter how severe is head injury during pregnancy, it can threaten both- the maternal and (or) the fetal life. The risk derives from systemic and cerebral consequences of high intracranial pressure, hypotension, anemia or expanding mass lessions in the cranial cavity. The specific hormonal background of the mother may contribute the better outcome after traumatic brain injury (TBI). Pregnancy and trauma push the doctors to create different and specific management than the usual case. Investigating literature data we figure out the initial assessment, management priorities for resuscitation of the head injured pregnant patient, concidering the specific anatomic and physiologic changes during pregnancy. We accept the principal: first save the mother, then the child, if possible, proposing algorithm for severe head injured pregnant patient management.

Pathophysiological mechanisms of impaired limb use and repair strategies for motor systems after unilateral injury of the developing brain.

The corticospinal tract (CST) is important for limb control. In humans, it begins developing prenatally but CST connections do not have a mature pattern until about 6 months of age and its capacity to evoke muscle contraction does not mature until mid-adolescence. An initially bilateral projection is subsequently refined, so that most ipsilateral CST connections are eliminated. Unilateral brain damage during refinement leads to bilateral developmental impairments. The damaged side develops sparse and weak contralateral spinal connections and the non-involved hemisphere maintains its ipsilateral projection to develop an aberrant bilateral spinal projection. In a kitten model of unilateral spastic cerebral palsy, we replicate key features of the CST circuit changes: robust bilateral CST projections from the non-involved hemisphere, sparse contralateral connections from the affected hemisphere, and motor impairments. We discuss the role of activity-dependent synaptic competition in development of bilateral CSTs and consider several experimental strategies for restoring a more normal pattern of CST connections from the damaged and non-involved sides. We highlight recent results stressing the importance of combined repair of CST axons, restoration of a more normal motor cortex motor representation, and key involvement of spinal cholinergic interneurons in restoring skilled motor function.

[Pregnancy and trauma].

Anatomic and physiologic changes in pregnancy can mask or mimic injury, making diagnosis of trauma-related problems difficult. Care of pregnant trauma patients with severe injuries often requires a multidisciplinary approach involving an emergency clinician, trauma surgeon, obstetrician, anesthesiologist and neonatologist. The pregnant trauma patient presents a unique challenge because care must be provided for two patients--the mother and the fetus.

Fetal laceration injury during cesarean section and its long-term sequelae: a case report.

This case report illustrates the cosmetic outcome of a scalpel-related laceration injury sustained to a newborn infant that occurred during the course of an elective cesarean section for breech presentation. This buttock laceration was noted to be 2 cm in length at the time of birth. Twelve years later, the same scar had migrated in a cephalad direction and had increased to 10 cm in length.

Trauma in pregnancy.

In the United States, trauma is the leading nonobstetric cause of maternal death. The principal causes of trauma in pregnancy include motor vehicle accidents, falls, assaults, homicides, domestic violence, and penetrating wounds. The managing team evaluating and coordinating the care of the pregnant trauma patient should be multidisciplinary so that it is able to understand the physiologic changes in pregnancy. Blunt trauma to the abdomen increases the risk of placental abruption. Evaluation of the pregnant trauma patient requires a primary and secondary survey with emphasis on airway, breathing, circulation, and disability. The use of imaging studies, invasive hemodynamics, critical care medications, and surgery, if necessary, should be individualized and guided by a coordinating team effort to improve maternal and fetal conditions. A clear understanding of gestational age and fetal viability should be documented in the record.

The four most common pediatric immunodeficiencies.

The four most common immunodeficiencies in pediatric patients are transient hypogamma-globulinemia of infancy, IgG subclass deficiency, impaired polysaccharide responsiveness (partial antibody deficiency) and selective IgA deficiency. Most of these patients have normal cellular immune systems, phagocyte function and complement levels. All four illnesses are characterized by recurrent bacterial respiratory infections such as purulent rhinitis, sinusitis, otitis and bronchitis. Except for some IgA-deficient patients, the molecular basis for these illnesses is not known, and indeed each syndrome is heterogeneous, with multiple causes, including genetic factors, drug/environmental toxicant exposure, and/or prenatal physiological events. This paper describes the clinical and laboratory features, postulated causes, current management and prognosis. Only a few of these cases require the use of intravenous IgG (IVIG) and the outlook for long life is excellent.

Complete fetal transection after a motor vehicle collision.

BACKGROUND: Motor vehicle collisions are the leading cause of fetal death related to maternal trauma, with rupture of the gravid uterus being one potential grave outcome. CASE: We present a case of a woman at 22 weeks of gestation who presented to the emergency department after a "high-speed" motor vehicle collision. On initial presentation, she was hemodynamically stable, and the examination was significant for midabdominal transverse ecchymosis from seatbelt trauma. A computed tomography scan identified a probable uterine rupture. Laparotomy revealed a 1,500-mL hemoperitoneum and a completely ruptured uterus requiring hysterectomy. The fetus was completely transected at the level of the midabdomen. CONCLUSION: Uterine rupture is possible for gravid women involved in motor vehicle collisions.

Trauma during pregnancy.

Trauma is the leading nonobstetrical cause of maternal death. The effect of trauma on the pregnant woman and unborn fetus can be devastating. The major causes of maternal injury are blunt trauma, penetrating trauma, burns, falls, and assaults. There are specific changes associated with pregnancy that are important for the clinician to consider when providing care to these patients. Initial management of traumatic injuries during pregnancy is essential for maternal and fetal well-being. This review outlines common causes of maternal trauma, the initial assessment of the pregnant trauma patient, and ongoing care for the pregnant trauma patient and unborn fetus.

Intrauterine penetrating direct fetal head trauma following gunshot injury: a case report and review of the literature.

CASE REPORT: An unusual case of an intrauterine penetrating head injury due to a pellet from an airgun is described. A 28-year-old pregnant woman, at term, shot herself intravaginally with a toy BB gun. Following a spontaneous precipitous vaginal delivery, the neonate presented with persistent seizure disorder, meningitis, cerebritis, and a right parietal region scalp swelling. Imaging studies revealed intracranial hemorrhage, and the metallic pellet was adjacent to the right lateral ventricle, which was removed through a parietal craniotomy. Computed tomography of the brain after 1 week demonstrated early abscess formation in the left frontal operculum and a subdural empyema in the posterior fossa. The abscesses were evacuated, and the meningitis was treated vigorously with broad-spectrum antibiotics. Although well for the past 6 years, the child demonstrates significant mental handicap and developmental delay. DISCUSSION: The pathogenesis, management, and medicolegal issues pertaining to the above case are discussed, and the relevant literature is briefly reviewed.