Yaozhi Wang

Neural stem cells (NSCs) differentiate into both neurons and glia, and strategies using human NSCs have the potential to restore function following spinal cord injury (SCI). However, the time period of maturation for human NSCs in adult injured CNS is not well defined, posing fundamental questions about the design and implementation of NSC-based therapies. This work assessed human H9 NSCs that were implanted into sites of SCI in immunodeficient rats over a period of 1.5 years. Notably, grafts showed evidence of continued maturation over the entire assessment period. Markers of neuronal maturity were first expressed 3 months after grafting. However, neurogenesis, neuronal pruning, and neuronal enlargement continued over the next year, while total graft size remained stable over time. Axons emerged early from grafts in very high numbers, and half of these projections persisted by 1.5 years. Mature astrocyte markers first appeared after 6 months, while more mature oligodendrocyte markers were not present until 1 year after grafting. Astrocytes slowly migrated from grafts. Notably, functional recovery began more than 1 year after grafting. Thus, human NSCs retain an intrinsic human rate of maturation, despite implantation into the injured rodent spinal cord, yet they support delayed functional recovery, a finding of great importance in planning human clinical trials.

We show that it is feasible to monitor the synchronized population spikes of the thalamocortical axonal terminals and cortical neurons outside the brain using high-resolution magnetoencephalography (MEG). Electrical stimulation of the snout elicited somatic-evoked magnetic fields (SEFs) above the primary somatosensory cortex (SI) of the piglet. The SEFs contained high-frequency oscillations (HFOs) around 600 Hz similar in many respects to the noninvasively measured HFOs from humans with MEG and electroencephalography (EEG). These HFOs were highly correlated with those in simultaneously measured intracortical somatic-evoked potentials (SEPs) in the snout projection area in SI. Both HFOs in SEFs and SEPs consisted of an initial component insensitive to cortically injected kynurenic acid (Kyna, 20 mM), a nonspecific antagonist of glutamatergic receptors, and a subsequent Kyna-sensitive component. The former was localized in cortical layer IV, indicating that it was due to spikes produced by the specific thalamocortical axonal terminals, whereas the latter was initially localized in layer IV and subsequently in the superficial and deeper layers. These results suggest that it may be possible to study properties of the thalamocortical and cortical spike activities in humans with MEG.