The low safety factor of demyelinated axons means that conduction along the axons is not only particularly sensitive to changes in temperature but also vulnerable to chemical factors that may impair conduction. For example, conduction may be perturbed if an imbalance occurs in the normal composition of the extracellular fluid bathing axons, such as may arise from impairments in the blood-brain barrier. It is suspected that this imbalance can include the appearance of factors that directly affect axonal physiology. Historically, there has been much interest in serum-derived neuroelectric blocking factors that were found to impair different types of neurophysiological function (reviewed in Smith, 1994), but the identity of the factors remained elusive, results were inconsistent, and interest in them waned. More recently, however, interest in the topic has been revived by evidence suggesting that factors associated with inflammation may be able to produce brief exacerbations in patients with MS (Moreau et al., 1996), apparently by acutely and reversibly blocking conduction in demyelinated axons. Nitric oxide has been identified as a candidate for mediating the acute and reversible block (Redford et al., 1997; Shrager et al., 1998; Garthwaite et al., 1999) (see Chapter 18), as has a pentapeptide with the sequence QYNAD (Brinkmeier et al., 2000; Meuth et al., 2003; Weber et al., 2002). Both factors are reported to be present in MS cerebrospinal fluid, and also to impair both axonal conduction and the function of sodium channels. The findings with nitric oxide have been reproduced in different laboratories, but those relating to QYNAD have been questioned (Cummins et al., 2003; Quasthoff et al., 2003). The factors are discussed in Chapter 18 (nitric oxide) and Chapter 22 (QYNAD).
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