Insulin-producing cells from mesenchymal stromal cells: Protection against cognitive impairment in diabetic rats depends upon implant site
LIFE SCIENCES
Authors: Wartchow, Krista Mineia; Rodrigues, Leticia; Lissner, Lilian Juliana; Federhen, Barbara Carolina; Selistre, Nicholas Guerini; Moreira, Aline; Goncalves, Carlos-Alberto; Sesterheim, Patricia
Abstract
Diabetes mellitus (DM) is a serious public health problem and can cause long-term damage to the brain, resulting in cognitive impairment in these patients. Insulin therapy for type 1 DM (DM1) can achieve overall blood glucose control, but glycemic variations can occur during injection intervals, which may contribute to some complications. Among the additional therapies available for DM1 treatment is the implantation of insulin-producing cells (IPCs) to attenuate hyperglycemia and even reverse diabetes. Here, we studied the strategy of implanting IPCs obtained from mesenchymal stromal cells (MSCs) from adipose tissue, comparing two different IPC implant sites, subcapsular renal (SR) and subcutaneous (SC), to investigate their putative protection against hippocampal damage, induced by STZ, in a rat DM1 model. Both implants improved hyperglycemia and reduced the serum content of advanced-glycated end products in diabetic rats, but serum insulin was not observed in the SC group. The SC-implanted group demonstrated ameliorated cognitive impairment (evaluated by novel object recognition) and modulation of hippocampal astroglial reactivity (evaluated by S100B and GFAP). Using GFP + cell implants, the survival of cells at the implant sites was confirmed, as well as their migration to the pancreas and hippocampus. The presence of undifferentiated MSCs in our IPC preparation may explain the peripheral reduction in AGEs and subsequent cognitive impairment recovery, mediated by autophagic depuration and immunomodulation at the hippocampus, respectively. Together, these data reinforce the importance of MSCs for use in neuroprotective strategies, and highlight the logistic importance of the subcutaneous route for their administration.
Validation of the scandinavian guidelines for initial management of minor and moderate head trauma in children
EUROPEAN JOURNAL OF TRAUMA AND EMERGENCY SURGERY
Authors: Sonnerqvist, Caroline; Brus, Ole; Olivecrona, Magnus
Abstract
Background Head trauma in children is common, with a low rate of clinically important traumatic brain injury. CT scan is the reference standard for diagnosis of traumatic brain injury, of which the increasing use is alarming because of the risk of induction of lethal malignancies. Recently, the Scandinavian Neurotrauma Committee derived new guidelines for the initial management of minor and moderate head trauma. Our aim was to validate these guidelines. Methods We applied the guidelines to a population consisting of children with mild and moderate head trauma, enrolled in the study: "Identification of children at very low risk of clinically-important brain injuries after head trauma: a prospective cohort study" by Kuppermann et al. (Lancet 374(9696):1160-1170,, 2009). We calculated the negative predictive values of the guidelines to assess their ability to distinguish children without clinically-important traumatic brain injuries and traumatic brain injuries on CT scans, for whom CT could be omitted. Results We analysed a population of 43,025 children. For clinically-important brain injuries among children with minimal head injuries, the negative predictive value was 99.8% and the rate was 0.15%. For traumatic findings on CT, the negative predictive value was 96.9%. Traumatic finding on CT was detected in 3.1% of children with minimal head injuries who underwent a CT examination, which accounts for 0.45% of all children in this group. Conclusion Children with minimal head injuries can be safely discharged with oral and written instructions. Use of the SNC-G will potentially reduce the use of CT.