Clinical recovery from stroke lesions and related outcomes.

Stroke lesions affect neurological status and are a critical determinant of treatment. This study investigated stroke lesions in terms of clinical recovery and related outcomes. Twenty-seven stroke patients were assessed via longitudinal observational study. Brain lesions were evaluated using MRI. The Fugl-Meyer Assessment and clinical evaluations were performed monthly between 1 and 6months after onset. The anterior limb (ICAL) and genu (ICG) of the internal capsule were associated with recovery of the upper limbs in chronic stroke patients. Involvement of the anterior half of the middle third of the corona radiata, the ICAL, the ICG, and the caudate nucleus were related to recovery of the lower limbs. Involvement of the middle third of the corona radiata, the ICAL, the ICG, and the lentiform nucleus were associated with sensory recovery. Clinical recovery from stroke, in terms of motor and sensory function, was related to injury in several white matter areas, such as the corona radiata and internal capsule, and was also associated with the basal ganglia as a gait pattern generator. Clinicians should be aware of stroke lesions, and should design therapeutic strategies accordingly, also with respect to treatment duration.

Descending propriospinal neurons mediate restoration of locomotor function following spinal cord injury.

Following spinal cord injury (SCI) in the lamprey, there is virtually complete recovery of locomotion within a few weeks, but interestingly, axonal regeneration of reticulospinal (RS) neurons is mostly limited to short distances caudal to the injury site. To explain this situation, we hypothesize that descending propriospinal (PS) neurons relay descending drive from RS neurons to indirectly activate spinal central pattern generators (CPGs). In the present study, the contributions of PS neurons to locomotor recovery were tested in the lamprey following SCI. First, long RS neuron projections were interrupted by staggered spinal hemitransections on the right side at 10% body length (BL; normalized from the tip of the oral hood) and on the left side at 30% BL. For acute recovery conditions (≤1 wk) and before axonal regeneration, swimming muscle burst activity was relatively normal, but with some deficits in coordination. Second, lampreys received two spaced complete spinal transections, one at 10% BL and one at 30% BL, to interrupt long-axon RS neuron projections. At short recovery times (3-5 wk), RS and PS neurons will have regenerated their axons for short distances and potentially established a polysynaptic descending command pathway. At these short recovery times, swimming muscle burst activity had only minor coordination deficits. A computer model that incorporated either of the two spinal lesions could mimic many aspects of the experimental data. In conclusion, descending PS neurons are a viable mechanism for indirect activation of spinal locomotor CPGs, although there can be coordination deficits of locomotor activity. NEW & NOTEWORTHY: In the lamprey following spinal lesion-mediated interruption of long axonal projections of reticulospinal (RS) neurons, sensory stimulation still elicited relatively normal locomotor muscle burst activity, but with some coordination deficits. Computer models incorporating the spinal lesions could mimic many aspects of the experimental results. Thus, after disruption of long-axon projections from RS neurons in the lamprey, descending propriospinal (PS) neurons appear to be a viable compensatory mechanism for indirect activation of spinal locomotor networks.

Microglia modulate respiratory rhythm generation and autoresuscitation.

Inflammation has been linked to the induction of apneas and Sudden Infant Death Syndrome, whereas proinflammatory mediators inhibit breathing when applied peripherally or directly into the CNS. Considering that peripheral inflammation can activate microglia in the CNS and that this cell type can directly release all proinflammatory mediators that modulate breathing, it is likely that microglia can modulate breathing generation. It might do so also in hypoxia, since microglia are sensitive to hypoxia, and peripheral proinflammatory conditions affect gasping generation and autoresuscitation. Here, we tested whether microglial activation or inhibition affected respiratory rhythm generation. By measuring breathing as well as the activity of the respiratory rhythm generator (the preBötzinger complex), we found that several microglial activators or inhibitors, applied intracisternally in vivo or in the recording bath in vitro, affect the generation of the respiratory rhythms both in normoxia and hypoxia. Furthermore, microglial activation with lipopolysaccharide affected the ability of the animals to autoresuscitate after hypoxic conditions, an effect that is blocked when lipopolysaccharide is co-applied with the microglial inhibitor minocycline. Moreover, we found that the modulation of respiratory rhythm generation induced in vitro by microglial inhibitors was reproduced by microglial depletion. In conclusion, our data show that microglia can modulate respiratory rhythm generation and autoresuscitation.

A dual spinal cord lesion paradigm to study spinal locomotor plasticity in the cat.

After a complete spinal cord injury (SCI) at the lowest thoracic level (T13), adult cats trained to walk on a treadmill can recover hindlimb locomotion within 2-3 weeks, resulting from the activity of a spinal circuitry termed the central pattern generator (CPG). The role of this spinal circuitry in the recovery of locomotion after partial SCIs, when part of descending pathways can still access the CPG, is not yet fully understood. Using a dual spinal lesion paradigm (first hemisection at T10 followed three weeks after by a complete spinalization at T13), we showed that major changes occurred in this locomotor spinal circuitry. These plastic changes at the spinal cord level could participate in the recovery of locomotion after partial SCI. This short review describes the main findings of this paradigm in adult cats.