**Neuroprotection and Recovery in Multiple Sclerosis**

Dafin F. Muresanu, Maria Balea, Olivia Rosu, Anca Buzoianu and Dana Slavoaca

Additional information is available at the end of the chapter

http://dx.doi.org/10.5772/63829

#### **Abstract**

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280 Trending Topics 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 ap‐ proved disease-modifying drugs (DMDs) are immunomodulatory or immunosuppres‐ sive, 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 remyelina‐ tion strategies. However, to date, attempts to provide neuroprotection have failed not just in multiple sclerosis but in neurological disorders in general; this situation has empha‐ sized 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.

**Keywords:** multiple sclerosis, neuroprotection, ion channel modulation, remyelina‐ tion, systems biology

#### **1. Introduction**

Multiple sclerosis (MS) is characterized by complex interactions between pathological path‐ ways and heterogeneity regarding lesions, progression, clinical symptoms, and immune responses.

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Recently, significant advances in MS therapy have been made, but these advances have been limited to the prevention of relapse, and long-term results are conflicting.

Understanding of endogenous defense activity (**Figure 1**), including neurotrophicity, neuro‐ protection, neuroplasticity, neurogenesis, and remyelination, is essential for pharmacological neuroprotection and enhanced neurorecovery. Neurotrophicity includes the processes necessary for the maintenance of a normal phenotype. Neuroprotection is the sum of all processes aimed at counterbalancing the pathophysiological mechanisms that are induced by the alteration of neuro-immune responses. Neuroplasticity represents the sum of the structural and functional changes that must occur for adaptation to new internal or environmental stimuli. Neurogenesis, in a broad sense, refers to the capacity of brain tissue to generate new neurons, astrocytes, and oligodendrocytes [1]. Remyelination is a physiological regenerative process that requires the activation of oligodendrocyte precursor cells (OPCs), their migration, recruitment, and differentiation into remyelinating oligodendrocytes and their interaction with denuded axons. Changes in these steps, which are characteristic of MS, promote neuro‐ degeneration.

**Figure 1.** Endogenous defense activity and damage mechanism.

Classical neuroprotection approaches include the use of the already Food and Drug Admin‐ istration (FDA)-approved disease modifying drugs (DMDs) and a wide spectrum of pharma‐ cological compounds that interact with one or more pathological processes (inflammation, oxidative damage, mitochondrial damage, and intracellular Ca2+ overload), as an attempt to prevent axonal degeneration. Pro-myelination therapies appear to be a promising approach, but several puzzle pieces regarding the physiology of remyelination, feasible treatment monitoring methods, the selection of patients, and the optimal time of treatment initiation remain unknown. However, neurodegeneration is not always related to demyelination, leading to the development of combination therapies that include agents that prevent neuro‐ degeneration, modulate neuroinflammation, and immune responses and promote remyelina‐ tion [2].
