2015 Round-up

Traumatic brain injury research highlights in 2015

Both chemical and physical microenvironments appear to be important for lineage specification of umbilical cord mesenchymal stem cells (UCMSCs). However, physical factors such as the elastic modulus in traumatic brain injury (TBI) are seldom studied. Intracranial hypertension and cerebral edema after TBI may change the brain’s physical microenvironment, which inhibits neural lineage specification of transplanted UCMSCs. The purpose of this study is to investigate the potential regulatory effect of mild hypothermia on the elastic modulus of the injured brain. First, we found that more UCMSCs grown on gels mimicking the elastic modulus of the brain (0.5 kPa) differentiated into neural cells, which were verified with the formation of branched cells and the expression of neural markers. Then, UCMSCs were transplanted into TBI rats, and we observed that mild hypothermia resulted in the differentiation of more neurons and astrocytes from transplanted UCMSCs. To demonstrate that more neural specification of UCMSCs was due to the regulation of the elastic modulus, we monitored intracranial pressure and cerebral edema. The results showed that mild hypothermia significantly reduced intracranial pressure and brain water content, indicating modulation of the elastic modulus by mild hypothermia. An examination with atomic force microscopy (AFM) in a cell injury model in vitro further verified hypothermia-regulated elastic modulus. In this study, we found a novel role of mild hypothermia in modulating the elastic modulus of the injured brain, resulting in the promotion of neural lineage specification of UCMSCs, which suggested that the combination of mild hypothermia had more advantages in cell-based therapy after TBI.

To effectively diagnose and treat women who have experienced intimate partner violence (IPV), it is important to identify the full range of physical and mental health consequences, including hidden wounds such as traumatic brain injury (TBI) and posttraumatic stress disorder (PTSD). We aimed to identify the occurrence of IPV-related TBI and associated PTSD symptoms among women veterans who experienced IPV.

A web-based survey was administered in 2014 to a national sample of U.S. women veterans. Among 411 respondents (75% participation rate), 55% reported IPV during their lives. These participants (N = 224) completed screening measures of IPV-related TBI, PTSD, and past-year IPV and comprised the current sample.

A total of 28.1% (n = 63) met criteria for IPV-related TBI history, and 12.5% (n = 28) met criteria for IPV-related TBI with current symptoms. When adjusting for race, income, and past-year IPV, women with IPV-related TBI with current symptoms were 5.9 times more likely to have probable IPV-related PTSD than those with no IPV-related TBI history. Despite symptom overlap between TBI and PTSD, women with IPV-related TBI with current symptoms were significantly more likely to meet criteria for all four DSM-5 PTSD symptom clusters compared to women with an IPV-related TBI history without current symptoms (Cramér's V′s = .34–.42).

Findings suggest there may be clinical utility in screening women who experience lifetime IPV for both TBI and PTSD symptoms in order to help clinicians better target their examinations, treatment, and referrals.

Erythropoietin (EPO) is an erythropoiesis stimulating growth factor and hormone. EPO has been widely used in the treatment of chronic renal failure, cancer, and chemotherapy-related anemia for three decades. However, many clinical trials showed that EPO treatment may be associated with tumorigenesis and cancer progression. EPO is able to cross blood–brain barriers, and this may lead to an increased possibility of central nervous system tumors such as glioblastoma. Indeed, EPO promotes glioblastoma growth and invasion in animal studies. Additionally, EPO increases glioblastoma cell survival, proliferation, migration, invasion, and chemoresistancy in vitro. However, the exact mechanisms of cancer progression induced by EPO treatment are not fully understood. Posttranscriptional gene regulation through microRNAs may contribute to EPO's cellular and biological effects in tumor progression. Here, we aimed to study whether tumor suppressive microRNA, miR-451, counteracts the positive effects of EPO on U87 human glioblastoma cell line. Migration and invasion were evaluated by scratch assay and transwell invasion assay, respectively. We found that EPO decreased basal miR-451 expression and increased cell proliferation, migration, invasion, and cisplatin chemoresistancy in vitro. miR-451 overexpression by transfection of its mimic significantly reversed these effects. Furthermore, ectopic expression of miR-451 inhibited expression of its own target genes, such as metalloproteinases-2 and -9, which are stimulated by EPO treatment and involved in carcinogenesis processes, especially invasion. These findings suggest that miR-451 mimic delivery may be useful as adjuvant therapy in addition to chemotherapy and anemia treatment by EPO and should be tested in experimental glioblastoma models.