Congenital Muscular Dystrophy 1D Causes Matrix Metalloproteinase Activation And Blood-Brain Barrier Impairment.

Congenital Muscular Dystrophy type 1D (CMD1D) is characterized by an abnormal glycosylation of α-DG (α-dystroglycan) and is associated to the central nervous system (CNS) abnormalities such as cognitive impairment. The purpose of the research was to evaluate the blood-brain barrier permeability (BBB) permeability and matrix metalloproteinases (MMP) -2 and -9 in adult Largemyd-/- mice in order to understand the physiopathology of brain involvement during the CMD1D process. To this aim, we used adult homozygous Largemyd-/- (mutation in Large), heterozygous Largemyd+/- as well as wild-type (C57BL/6) mice. The animals were submitted to the evaluation of BBB permeability and MMP-2 and MMP-9 in striatum, hippocampus and cerebral cortex. There was an increase in BBB permeability in the hippocampus and striatum associated with an increase in the protein levels of MMP-2 in the cerebral cortex and striatum and MMP-9 in the hippocampus in adult Largemyd-/- mice. Our results suggest that the pathophysiologic processes can be associated to the action of MMPs and BBB disruption and that the BBB breakdown is relevant to the perpetuation of brain inflammation and can be related to brain dysfunction observed in CMD1D patients.

Experimental Neonatal Sepsis Causes Long-Term Cognitive Impairment.

Neonatal sepsis is a major cause of morbidity and mortality in neonatal intensive care units. Treatment with antibiotics reduces mortality and morbidity, but neonatal sepsis remains a serious life-threatening condition. The objective of this study was to evaluate cognitive impairment in adult mice submitted to sepsis in the neonatal period. To this aim, 2-day-old male C57BL/6 mice were submitted to sepsis by injection of 25 µg of LPS. Sixty days after, the learning and memory were evaluated. It was observed that the mice submitted to neonatal sepsis presented impairment of habituation, aversive, and object recognition memories, and had an increase of immobility time in forced swimming test in adulthood. In conclusion, this study shows that the neonatal sepsis causes long-term brain alterations. These alterations can persist to adulthood in an animal model due to a vulnerability of the developing brain.

Effect of sepsis on behavioral changes on the ketamine-induced animal model of schizophrenia.

This study aimed to evaluate the effect of sepsis on behavioral changes on the ketamine-induced animal model of schizophrenia. Male Wistar rats underwent Cecal Ligation and Perporation (CLP) with "basic support" or were sham-operated. After 30 days, the animals were submitted to a model of schizophrenia by injection of Ketamine. The behavior tests were performed after 30 min of the injection of Ketamine or saline. Ketamine in doses of 15 and 25mg/kg increased locomotor activity, latency to first contact in the social interaction and stereotyped behavior. Some changes caused by sepsis may be associated with a predisposition to develop schizophrenia in the animal model.