Brain Vol. 127 No. 12 © Guarantors of Brain 2004; all rights reserved
Editorial |
Editorial
‘Stem cells, stories and wonderful works’ is the collective title Alasdair Coles and Roger Barker use for their review of Neural stem cells for brain and spinal cord repair (edited by Tanya Zigova, Evan Snyder and Paul Sanberg), Still lives—narratives of spinal cord injury (by Jonathan Cole) and Stem cell research—new frontiers in science and ethics (edited by Nancy Snow). Capable both of self-renewal and differentiation down defined lineages in response to appropriate signals, stem cells have achieved fame well in advance of their performances in clinical medicine. Society expects a great deal, but has yet to resolve certain dilemmas. Christopher Reeve, who died from complications of spinal cord injury on October 10, 2004, 9 years after his riding accident, was an icon for paraplegics. Through the Christopher Reeve Paralysis Foundation, he sought to engender research and take forward the social and political agenda, in the face of some public and political approbation, and in response to scientific realism mixed with hyperbole. From Superman (1978), through to a number of less block-busting roles, his own fate was poignantly anticipated in Above Suspicion (1995) where he played a paraplegic policeman planning a couple of homicides. Later, his altered circumstances were undisguised in the re-making of Rear Window (1998). To the observer, he appeared intensely dignified and extremely courageous. Reeve, the person, and his campaign to accelerate research on stem cells became a political football in the recent US presidential campaign. Writing from positions of faith, Drs Coles and Barker lay out the ethical and clinical science issues that arise in deciding whether or not to harness the scientific potential of stem cell biology in the contemporary cultural and medical climates. They rehearse the personal stories and diverse attitudes of 12 people for whom neural stem cells might offer a solution to severe disability. Paradoxically, not all want this (or any other) treatment. This thoughtful analysis deserves to be widely read and discussed.
The narrators in Still lives have all suffered spinal cord injury, and they no longer expect spontaneous recovery. Vicki Anderson and colleagues (page 2608) correlate deficits of intellect, and language and memory functions, with the severity of traumatic brain injury and pre-morbid socio-economic status in childhood. Taking a longer view on insults to the developing nervous system, Elizabeth Isaacs et al. (page 2595) show that, despite no apparent neurological damage, focal injury of the frontal and temporal lobes in infants born at 
30 weeks is, by adolescence, associated with a detectable decline in intellect. However, Laury Chamelian, Marciano Reis and Anthony Feinstein (page 2621) qualify the old story suggesting that response to brain injury is determined by alleles of apolipoprotein (ApoE-
4); evidently, this seems not to hold up for mild traumatic brain injury, at least over the initial 6 months, using a variety of well validated cognitive and neuropsychological outcomes. How best and when to deploy treatments that protect defined cell types from injury is the focus of a paper by Xing Wei and colleagues (page 2629) who show that caffeic acid phenethyl ester is neuroprotective for rat neurons through inhibition of caspase 3-induced apoptosis and expression of inducible nitric oxide synthase, protecting the mitochondrion from calcium-mediated cytochrome c release. But can we extrapolate from such rodent studies to the human CNS? Not always; Karolina Wosik and others from the group of Jack Antel point out that the literature on AMPA/kainite receptor-mediated glutamatergic excitotoxic injury is true for rat but not human oligodendrocytes (page 2636)—as is true for several other forms of rat–human cell injury.
As the contributors to Still lives lament, movement is fundamental to human dignity. Guillermo Paradiso and colleagues (page 2717) use movement-related potentials captured in patients undergoing deep brain stimulation to show that the ventral lateral thalamus is involved early in the preparation of movement. Jill Moss and the group of Peter Bain (page 2755), reveal that, based on sampling tissue accreted to explanted electrodes, the needles elicit a foreign body inflammatory reaction irrespective of time in situ. Carsten Buhmann and colleagues from Hamburg (page 2732) report that the cortical plasticity, presumably acting to improve impoverished motor activity in the dorsal premotor cortex in drug-naïve patients with Parkinson's disease, is dopamine dependent and reversed by treatment. And on the topic of plasticity in Parkinson's disease, the erratic increase in striatal synaptic dopamine concentration (assessed by radioligands) triggered by a standard dose of levodopa may explain peak-dose dyskinesias (Raúl de la Fuente-Fernández et al., page 2747). Parkinson's disease and parkinsonism are currently experiencing much genetic, clinical, imaging-based and pathological splitting—providing evidence for complexity and heterogeneity. Tamas Revesz and colleagues have used pathological material from 100 tissue-banked cases of multiple system atrophy to perform semi-quantitative histological analyses at several brain regions of interest, correlating pathology with clinical phenotype and drug history (page 2567). Glial cytoplasmic inclusions are associated with increased neuronal loss and disease duration, especially in olivopontocerebellar atrophy. Conversely, neuronal loss is rapid, irrespective of glial pathology, in striatonigral degeneration. Neuronal cytoplasmic inclusions do not discriminate the different types of multiple system atrophy, and Lewy bodies are seen infrequently. Response to treatment is likely to have been poor in the context of severe putaminal involvement at autopsy. Shy and Drager (1960) first drew attention to the high frequency of autonomic involvement in striatonigral degeneration and olivopontocerebellar degeneration. David Oppenheimer coined the term ‘multiple system atrophy’ and with (Sir) Roger Bannister reported the early series of cases in Brain that we summarize in From the Archives.
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