LAUSR

The investigation of predictors and facilitators of stroke recovery constitutes one of the new frontiers in clinical neuroscience, firmly placing stroke recovery and brain repair within the continuum of care for stroke patients. It is for this reason that the National Institutes of Health has made stroke recovery one of the 3 pillars of the StrokeNet grant program. In a study published in the most recent issue of Annals of Neurology, Minnerup and colleagues used histological assessments, magnetic resonance imaging, and motor testing to examine motor recovery and its structural correlates in a novel rat model of brainstem stroke. Remarkable findings were the postlesional activation of a newly described neurogenic site in the dorsal brainstem and the structural reorganization of the corticorubrospinal system with its rubral relay station (possibly allowing crossed and uncrossed connections with the descending spinal system). Their findings are supported by previous studies showing evidence of neurogenesis in the floor of the 4th ventricle in rats and structural changes/remodeling of the red nucleus and its anatomical vicinity after lesion to the descending motor system. Both of their main findings deserve discussion to provide further perspective with regard to human stroke. First, the past 2 decades of research have demonstrated that new neurons are produced in the adult brain and that their production is facilitated after damage to the brain. Neurogenesis has reliably been proven to subsist in the 2 classic germinal niches of the mammalian brain across species: in the subventricular zone of the lateral ventricle and in the subgranular layer of the dentate gyrus. However, different animal studies have found evidence for neural stem cells in several so-called ectopic niches along the ventricular system such as the olfactory epithelium, the habenula, the ependyma of the central canal, and the area postrema. In animal models of focal cortical ischemia, increased proliferation and neurogenic differentiation was primarily found in the subventricular zone, but also in ectopic niches. Here, neuroblasts are generated that migrate to peri-infarct cortex, where few mature into neurons and most of them die within months. Thus, functional relevance may be mediated through the local production of growth factors, even more so in the model of brainstem stroke where neuroblasts did not mature into neurons after migration. Upregulation of neurogenesis in the dorsal brainstem with migration of neuroblasts to the peri-infarct zone has never been as convincingly shown as in the study by Minnerup and colleagues. Their study falls in the midst of a renewed discussion about whether adult neurogenesis occurs in the human hippocampus, which has been sparked by 2 recent studies with contrary results. However, the classic neurogenic niches are not activated by brainstem lesion, and the novelty of the current study is not only the discovery of an unknown neurogenic niche, but the observation that its lesion-induced activation follows the logic of anatomical proximity. Namely, lesion location seems to determine not only the deficit but also its potential recovery mechanisms. Second, Minnerup and colleagues have shown that neuronal repair is facilitated by the compensatory recruitment of uninjured brain regions and motor pathways. Compensation occurs when systems mediating complementary functions in a physiologically functioning network exhibit substitutional functions in a lesioned one. Whereas compensation in other systems of the brain such as the language system or the swallowing system relies on inherent capabilities of one hemisphere to take over functions of the injured hemisphere or on its rudimentary bihemispheric organization, this process does not seem to apply to the motor system. One potential reason is the hemispheric specialization and localization of function in the human brain, enabling speed and accuracy of volitional finger movements. Previous research has shown that most of the variability in motor outcome after a stroke is explained by the degree of injury to the descending pyramidal tract and initial motor impairment. Compensation and substitution have not been a major focus of this system in humans. However, the motor system might have some built-in redundancy such as the uncrossed pyramidal tract (which so far has only been shown to play a compensatory role in the developing but not the adult brain) 15 as well as more bilaterally organized extrapyramidal tracts such as