Safety of Special Waveform of Transcranial Electrical Stimulation (TES): In Vivo Assessment.

Intermittent theta burst (iTBS) powered by direct current stimulation (DCS) can safely be applied transcranially to induce neuroplasticity in the human and animal brain cortex. tDCS-iTBS is a special waveform that is used by very few studies, and its safety needs to be confirmed. Therefore, we aimed to evaluate the safety of tDCS-iTBS in an animal model after brain stimulations for 1 h and 4 weeks. Thirty-one Sprague Dawley rats were divided into two groups: (1) short-term stimulation for 1 h/session (sham, low, and high) and (2) long-term for 30 min, 3 sessions/week for 4 weeks (sham and high). The anodal stimulation applied over the primary motor cortex ranged from 2.5 to 4.5 mA/cm2. The brain biomarkers and scalp tissues were assessed using ELISA and histological analysis (H&E staining) after stimulations. The caspase-3 activity, cortical myelin basic protein (MBP) expression, and cortical interleukin (IL-6) levels increased slightly in both groups compared to sham. The serum MBP, cortical neuron-specific enolase (NSE), and serum IL-6 slightly changed from sham after stimulations. There was no obvious edema or cell necrosis seen in cortical histology after the intervention. The short- and long-term stimulations did not induce significant adverse effects on brain and scalp tissues upon assessing biomarkers and conducting histological analysis.

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.

Relevance of nerve conduction velocity in the assessment of balance performance in older adults with diabetes mellitus.

Purpose This study investigated the relationship between peripheral nerve conduction velocity (NCV) and balance performance in older adults with diabetes. Methods Twenty older adults with diabetes were recruited to evaluate the NCV of their lower limbs and balance performance. The balance assessments comprised the timed up and go (TUG) test, Berg balance scale (BBS), unipedal stance test (UST), multidirectional reach test (MDRT), maximum step length (MSL) test and quiet standing with eyes open and closed. The relationship between NCV and balance performance was evaluated by Pearson's correlation coefficients, and the balance performances of the diabetic patients with and without peripheral neuropathy were compared by using Mann-Whitney U tests. Results The NCV in the lower limbs exhibited a moderate to strong correlation with most of the balance tests including the TUG (r = -0.435 to -0.520, p < 0.05), BBS (r = 0.406-0.554, p < 0.05), UST (r = 0.409-0.647, p < 0.05) and MSL (r = 0.399-0.585, P < 0.05). In addition, patients with diabetic peripheral neuropathy had a poorer TUG (p < 0.05), BBS (p < 0.01), UST (p < 0.05) and MSL performance (p < 0.05) compared with those without peripheral neuropathy (p < 0.05). Conclusion Our findings revealed that a decline in peripheral nerve conduction in the lower limb is not only an indication of nerve dysfunction, but may also be related to the impairment of balance performance in patients with diabetes. Implications for Rehabilitation Nerve conduction velocity in the lower limbs of diabetic older adults showed moderate to strong correlations with most of the results of balance tests, which are commonly used in clinics. Decline in nerve conduction velocity of the lower limbs may be related to the impairment of balance control in patients with diabetes. Diabetic older adults with peripheral neuropathy exhibited greater postural instability than those without peripheral neuropathy.