Properdin: A Novel Target for Neuroprotection in Neonatal Hypoxic-Ischemic Brain Injury.

Background: Hypoxic-ischemic (HI) encephalopathy is a major cause of neonatal mortality and morbidity, with a global incidence of 3 per 1,000 live births. Intrauterine or perinatal complications, including maternal infection, constitute a major risk for the development of neonatal HI brain damage. During HI, inflammatory response and oxidative stress occur, causing subsequent cell death. The presence of an infection sensitizes the neonatal brain, making it more vulnerable to the HI damage. Currently, therapeutic hypothermia is the only clinically approved treatment available for HI encephalopathy, however it is only partially effective in HI alone and its application in infection-sensitized HI is debatable. Therefore, there is an unmet clinical need for the development of novel therapeutic interventions for the treatment of HI. Such an alternative is targeting the complement system. Properdin, which is involved in stabilization of the alternative pathway convertases, is the only known positive regulator of alternative complement activation. Absence of the classical pathway in the neonatal HI brain is neuroprotective. However, there is a paucity of data on the participation of the alternative pathway and in particular the role of properdin in HI brain damage. Objectives: Our study aimed to validate the effect of global properdin deletion in two mouse models: HI alone and LPS-sensitized HI, thus addressing two different clinical scenarios. Results: Our results indicate that global properdin deletion in a Rice-Vannucci model of neonatal HI and LPS-sensitized HI brain damage, in the short term, clearly reduced forebrain cell death and microglial activation, as well as tissue loss. In HI alone, deletion of properdin reduced TUNEL+ cell death and microglial post-HI response at 48 h post insult. Under the conditions of LPS-sensitized HI, properdin deletion diminished TUNEL+ cell death, tissue loss and microglial activation at 48 h post-HI. Conclusion: Overall, our data suggests a critical role for properdin, and possibly also a contribution in neonatal HI alone and in infection-sensitized HI brain damage. Thus, properdin can be considered a novel target for treatment of neonatal HI brain damage.

Computerized cognitive stimulation and engagement programs in older adults with mild cognitive impairment: comparing feasibility, acceptability, and cognitive and psychosocial effects.

PURPOSE: Mild cognitive impairment (MCI) is associated with a higher risk of dementia and is becoming a topic of interest for pharmacological and nonpharmacological interventions. With advances in technology, computer-based cognitive exercises are increasingly integrated into traditional cognitive interventions, such as cognitive training. Another type of cognitive intervention involving technology use is cognitive engagement, consisting of involving participants in highly motivational and mentally challenging activities, such as learning to use a form of new digital technology. This study examined the feasibility and acceptability of a computerized cognitive stimulation (CCS) program and a computerized cognitive engagement (CCE) program, and then compared their effects in older adults with MCI. PATIENTS AND METHODS: In this randomized study, data from 19 MCI patients were analyzed (n=9 in CCS and n=10 in CCE). The patients attended a group weekly session for a duration of 3 months. Assessments of cognitive and psychosocial variables were conducted at baseline (M0) and at the end of the programs (M3). RESULTS: All of the participants attended the 12 sessions and showed a high level of motivation. Attrition rate was very low (one dropout at M3 assessment). At M3, the CCS participants displayed a significant improvement in part B of the Trail Making Test (TMT-B; p=0.03) and self-esteem (p=0.005), while the CCE participants showed a significant improvement in part A of the Trail Making Test (TMT-A; p=0.007) and a higher level of technology acceptance (p=0.006). The two groups did not differ significantly (p>0.05) in cognitive and psychosocial changes after the intervention. However, medium effect sizes (Cohen's d=0.56; 95% CI =-0.43:1.55) were found on the free recall, favoring the CCS group, as well as on TMT-A (d=0.51; 95% CI =-0.48:1.49) and technology acceptance (d=-0.65; 95% CI =-1.64:0.34), favoring the CCE group. CONCLUSION: Both interventions were highly feasible and acceptable and allowed improvement in different aspects of cognitive and psychosocial functioning in MCI subjects.