Neuroprotection and Recovery in Multiple Sclerosis

Multiple sclerosis is a complex and heterogeneous immune-mediated disease that results in the progressive accumulation of mental and physical symptoms. Currently approved disease-modifying drugs (DMDs) are immunomodulatory or immunosuppressive, but these drugs have little effect on disease progression. In addition to studies that have directly targeted inflammation and immune responses, a large number of studies, most of them experimental, have investigated neuroprotective therapies and remyelination strategies. However, to date, attempts to provide neuroprotection have failed not just in multiple sclerosis but in neurological disorders in general; this situation has emphasized the need to revise the old paradigm of a “magic bullet” with a single mechanism of action. Remyelination strategies involve either promoting endogenous remyelination or replacing lost myelinating cells through exogenous sources. However, several puzzle pieces regarding the physiology of remyelination remain unknown, including feasible treatment monitoring methods, the selection of patients, and the optimal time of treatment initiation. This chapter will describe the direct and indirect neuroprotective effects of DMDs, as suggested by basic research studies and confirmed by clinical studies in some cases. Current knowledge of potential neuroprotective therapies and remyelination strategies is also reviewed

Rehabilitation and clinical evolution aspects in a case of Osteoid Osteoma

Abstract: Introduction. Osteoid osteoma represents about 3% of all primary bone tumors and 11% of all benign bone tumors. Data from the literature suggest that a neuromuscular rehabilitation program after osteoid osteoma surgery is very beneficial and improves the general quality of life. Material and methods. A 30-year-old male patient with intermittent right shoulder pain radiating to the right hand, and recurrent myalgias in the past year presented to our neuro-logical department. The neurological examination highlighted limitation of the abduction of the right upper limb. The paraclinical investigations included plain radiography of the right upper limb and electroneurography, which were normal, and native cervical MRI which revealed discrete C5 disc overflow, without visible signs of compression. The patient presented limited initial response to NSAIDs, so his treatment was changed to corticoster-oid therapy. Further, the patient was guided to undergo a rheumatological examination where a musculoskeletal ultrasound was performed, showing no any specific modifica-tion. Additionally, we indicated a native right shoulder MRI, which revealed a signal mod-ification of the proximal humeral diaphysis. We further indicated an MRI scan with con-trast of the upper right limb, which revealed a nidus at the top one-third of the humerus. Additionally, a CT scan with contrast of the same region displayed images that were high-ly suggestive of osteoma. The patient was referred to the orthopedics department, where a complete resection of the tumor was performed, and the pathology report confirmed the fi-nal diagnosis of osteoid osteoma. Conclusions. Recovery after osteoid osteoma surgery is more beneficial if the neuromuscu-lar rehabilitation program, that has an important role in increasing muscle strength, is combined with orthopedic devices and pain medication

Severe sensory ganglionopathy as a manifestation of mixed connective tissue disease

Sensory ganglionopathies (SG) are a rare but distinct clinical subgroup of peripheral neuropathies characterized by damage to dorsal root ganglia. Typical manifestations include early gait and limb ataxia, widespread diminished or absent deep tendon reflexes accompanied by Romberg sign and pseudoathetoid movements.The diagnosis of SG is valuable since it may prompt towards early recognition of an underlying malignancy or autoimmune disorder. We report the case of a female diagnosed with mixed connective tissue disease (MCTD) along with severe SG. To our knowledge, such disease association has not been reported yet. The pathophysiology in cases linked to MCTD is unclear and asks for further studies. Moreover, the important degree of disability associated with this condition highlights the need for effective therapies’ development

Advances and perspectives for Central Nervous System drug delivery: the interface between nanotechnology and neuroscience

EditorialAdvances and perspectives for Central Nervous System drug delivery: the interface between nanotechnology and neuroscience A report from the World Health Organization (WHO) recently highlighted that Central Nervous System (CNS) disorders (brain injuries, neuroinfections, multiple sclerosis, epilepsy, stroke, Alzheimer and Parkinson disease) are affecting more than one billion people worldwide (WHO, 2006). The majority of these diseases are almost untreatable or featured by poor prognosis, since only 2% of the overall drugs are able to enter the brain as the blood-brain barrier (BBB) restricts the diffusion of substances from blood to the brain (Pardridge, 2002). In recent years, the use of nanotechnology has been considered a valuable strategy in order to achieve the drug delivery to the brain (Pardridge, 2003; Kabanov, 2004; Gabathuler, 2010). Nanomedicine-based approach has deserved considerable results as some medicinal products have reached the phases I and II and some imaging nano-devices obtained the marketing authorization (Tosi et al., 2008). Thus, the research in this field of science has been featured by an increasing number of experimental strategies, in order to maximize and optimize the therapeutic protocols. This issue of Journal of Nanoneuroscience could be divided into two main chapter: one is dealing with the different kinds of approaches for BBB crossing and CNS targeting as nanomedicine-based strategies, nasal route for BBB crossing and gene delivery by carbon nanotubes. The other theme could be summarized as potential treatments and imaging of brain diseases, as glioma treatment by means of nanotech-based delivery of taxanes, quantum dots for imaging and gold nanoparticles with antioxidative effec

Size and age dependent Neurotoxicity of Engineered nanoparticles from metals in Rats. Role of Nitric oxide in brain pathology

Previous studies from our laboratory show that chronic administration of engineered nanoparticles from metals, e.g., Cu, Ag, or Al (50-60 nm, 50 mg/kg, i.p. daily for 1 week) are able to induce profound blood-brain barrier (BBB) disruption, brain edema formation and brain pathology in adult rats (age 18 to 22 weeks). This effect was most pronounced by Ag followed by Cu and Al indicating that the constituents of nanoparticles play crucial roles in neurotoxicity. However, effects of size dependent neurotoxicity of nanoparticles in vivo situation are still unknown. In present investigation, we examined the effects of different size ranges of engineered nanoparticles from Cu, Ag and Al on brain pathology in rats. In view of the fact that age is also an important factor in brain pathology, we also evaluated age-related neurotoxicity of nanoparticles in our rat model. Three different sizes of Cu, Ag or Al nanoparticles (20 to 30 nm; 50 to 60 nm, or 130 to 150 nm) were administered intraperitoneally (50 mg /kg, i.p.) in separate set of rats (n = 5 to 7) in 3 different age groups (9 to 10 weeks; 18 to 20 weeks or 30 to 35 weeks old). Saline treated rats served as controls. Breakdown of the BBB to Evans blue albumin (EBA) and radioiodine, brain water content, neuronal injury, astrocytic activation, myelin damages and nitric oxide synthase (NOS) immunoreactivity was examined using standard procedures. Our results showed that brain pathology caused by different nanoparticles were inversely related to their sizes. Thus, smaller nanoparticles from Ag, Cu or Al induced most pronounced BBB breakdown (EBA +480 to 680%; radioiodine +850 to 1025%), brain edema formation (+4 to 6 %) as well as neuronal injuries (+30 to 40%), glial fibrillary acidic protein (GFAP) upregulation (+40 to 56% increase) and myelin vesiculation (+30 to 35 % damage) in youngest animals compared to controls. Interestingly, the oldest animals (30 to 35 weeks of age) also showed massive brain pathology as compared to young adults (18 to 20 weeks old). The Ag and Cu exhibited greater brain damage compared from Al nanoparticles in all age groups regardless of their sizes. This confirms that the composition of nanoparticles is important in neurotoxicity. The very young and elderly age groups exhibited greater neurotoxicity to nanoparticles suggests that children and elderly are more vulnerable to nanoparticles induced brain damage. The nanoparticles induced brain damage correlated well with the upregulation of neuronal and inducible NOS activity in the brain indicating that nanoparticles induced size and age dependent neurotoxicity could probably mediated via increased production of nitric oxide, not reported earlier

Need to Explore Nanodelivery of Stem Cells with Multimodal Drug like Cerebrolysin for Effective Strategies for Enhanced Neuroprotection and Neurorecovery in Neurodegenerative Disorders

Central nervous system (CNS) is vulnerable to various kinds of physical, chemical, metabolic or age-related insults leading to neurodegeneration. Neurodegenerative diseases either caused by aging or following trauma to the CNS results in misery for large number of people across the Globe involving high social costs for them to maintain a good life [1]. Thus, there is an urgent need to find novel solutions to reduce the burden of neurodegenerative disease induced problems in our aging populations. In this context, Alzheimer’s disease (AD) is causing huge social burden for the victims as no such therapy available for them to improve their lifetime disabilities [2,3]. This is especially critical to Military personnel who are the victims of brain or spinal cord injuries during combat operations [4]. There are reasons to believe that primary CNS injury could accelerate development of AD or Parkinson’s Diseases (PD) over time apart from post-traumatic stress disorders (PTSD) [5]. More often our young victims could also be critical following traumatic injuries to their CNS either following motor vehicle accidents or during combat operations in the battlefield [4]. All these young and old populations require a healthy life.</p