Human platelet lysate biotherapy for traumatic brain injury: preclinical assessment.

Traumatic brain injury (TBI) leads to major brain anatomopathological damages underlined by neuroinflammation, oxidative stress and progressive neurodegeneration, ultimately leading to motor and cognitive deterioration. The multiple pathological events resulting from TBI can be addressed not by a single therapeutic approach, but rather by a synergistic biotherapy capable of activating a complementary set of signalling pathways and providing synergistic neuroprotective, anti-inflammatory, antioxidative, and neurorestorative activities. Human platelet lysate might fulfil these requirements as it is composed of a plethora of biomolecules readily accessible as a TBI biotherapy. In the present study, we tested the therapeutic potential of human platelet lysate using in vitro and in vivo models of TBI. We first prepared and characterized platelet lysate from clinical-grade human platelet concentrates. Platelets were pelletized, lysed by three freeze-thaw cycles, and centrifuged. The supernatant was purified by 56°C 30 min heat treatment and spun to obtain the heat-treated platelet pellet lysate that was characterized by ELISA and proteomic analyses. Two mouse models were used to investigate platelet lysate neuroprotective potential. The injury was induced by an in-house manual controlled scratching of the animals' cortex or by controlled cortical impact injury. The platelet lysate treatment was performed by topical application of 60 µl in the lesioned area, followed by daily 60 µl intranasal administration from Day 1 to 6 post-injury. Platelet lysate proteomics identified over 1000 proteins including growth factors, neurotrophins, and antioxidants. ELISA detected several neurotrophic and angiogenic factors at ∼1-50 ng/ml levels. We demonstrate, using two mouse models of TBI, that topical application and intranasal platelet lysate consistently improved mouse motor function in the beam and rotarod tests, mitigated cortical neuroinflammation, and oxidative stress in the injury area, as revealed by downregulation of pro-inflammatory genes and the reduction in reactive oxygen species levels. Moreover, platelet lysate treatment reduced the loss of cortical synaptic proteins. Unbiased proteomic analyses revealed that heat-treated platelet pellet lysate reversed several pathways promoted by both controlled cortical impact and cortical brain scratch and related to transport, postsynaptic density, mitochondria or lipid metabolism. The present data strongly support, for the first time, that human platelet lysate is a reliable and effective therapeutic source of neurorestorative factors. Therefore, brain administration of platelet lysate is a therapeutical strategy that deserves serious and urgent consideration for universal brain trauma treatment.

Dementia beyond 2025: Knowledge and uncertainties.

Given that there may well be no significant advances in drug development before 2025, prevention of dementia-Alzheimer's disease through the management of vascular and lifestyle-related risk factors may be a more realistic goal than treatment. Level of education and cognitive reserve assessment in neuropsychological testing deserve attention, as well as cultural, social, and economic aspects of caregiving. Assistive technologies for dementia care remain complex. Serious games are emerging as virtual educational and pleasurable tools, designed for individual and cooperative skill building. Public policies are likely to pursue improving awareness and understanding of dementia; providing good quality early diagnosis and intervention for all; improving quality of care from diagnosis to the end of life, using clinical and economic end points; delivering dementia strategies quicker, with an impact on more people. Dementia should remain presented as a stand-alone concept, distinct from frailty or loss of autonomy. The basic science of sensory impairment and social engagement in people with dementia needs to be developed. E-learning and serious games programs may enhance public and professional education. Faced with funding shortage, new professional dynamics and economic models may emerge through coordinated, flexible research networks. Psychosocial research could be viewed as an investment in quality of care, rather than an academic achievement in a few centers of excellence. This would help provide a competitive advantage to the best operators. Stemming from care needs, a logical, systems approach to dementia care environment through organizational, architectural, and psychosocial interventions may be developed, to help reduce symptoms in people with dementia and enhance quality of life. Dementia-friendly environments, culture, and domesticity are key factors for such interventions.

A new decision tree combining Abeta 1-42 and p-Tau levels in Alzheimer's diagnosis.

The objective of this work was to improve the clinical diagnosis of Alzheimer's disease (AD) by proposing a simple decision tree based on three major biomarkers of AD found in the cerebrospinal fluid (CSF): amyloid peptide Aß1- 42, total Tau (t-Tau) and Tau phosphorylated at Thr181 (p-Tau). Two consecutive cohorts comprising 548 patients in total were recruited by the Memory and Neurology Clinics at Lille University Hospital (France). These included 293 patients with AD, 171 patients with other dementias and 84 healthy controls. All patients underwent lumbar puncture for the assessment of CSF concentrations of Aß1-42, t-Tau and p-Tau. International criteria for dementias were used for diagnosis by investigators blind to CSF test results. To identify the combination of biomarkers that best predicted the 3 diagnoses, we used the CHAID decision tree method with the first cohort. Our analysis yielded a two-step decision tree, with a first stratification step based on the Aß1-42/p-Tau ratio of the CSF, and a second step based on CSF p-Tau concentrations. The second cohort was then used to determine the power (0.618), sensitivity (82%) and specificity (81%) of this tree in AD diagnosis. These were found to be at least as high as those of other known algorithms based on the three CSF biomarkers, Aß1-42, t-Tau and p-Tau.For the first time, diagnostic rules for AD based on CSF variables were compared in a single study. Our findings indicate that the measurement of Aß1-42 and p-Tau levels in the CSF is sufficient to diagnose AD.