Toxicity of CSF in motor neurone disease: a potential route to neuroprotection

The paper by Tikka and colleagues in this issue of Brain reports that CSF from patients with motor neurone disease (MND) is toxic to cultured spinal cord neurones and that the tetracycline antibiotic minocycline exerts a significant neuroprotective effect against this toxicity (Tikka et al ., 2002).There is a tendency in MND for the disease to start focally, for example with weakness of one hand, unilateral foot drop or dysarthria. As judged by clinical signs of progression, the disease typically tends to spread to contiguous groups of motor neurones. There has been great interest in the possible diffusible factors which may contribute to this propagation of neuronal injury between adjacent groups of motor neurones. Potential candidates include nitric oxide; free radical species or toxic chemicals resulting from free radical reactions such as 4‐OH nonenal; molecules released from activated microglia, as well as an increase in the extracellular level of the excitatory neurotransmitter glutamate. The toxic factors may be detectable in CSF, the composition of which reflects changes in the chemistry of the extracellular space in the CNS.There have been several previous studies that demonstrate the toxicity to neurones in culture of the CSF from MND patients (Terro et al ., 1996; Couratier et al ., 1993; Manabe et al ., 1999). CSF toxicity has also been reported in some other neurodegenerative disorders, for example, Hao and co‐workers reported that CSF from patients with Parkinson’s disease selectively inhibited the growth and function of dopaminergic neurones in culture (Hao et al ., …