The brain stores the data of the mind. Restoration of the aged brain will be the most challenging portion of the development of a comprehensive toolkit of rejuvenation therapies, if only because we (largely) cannot resort to outright replacement of component parts, as is the case for the rest of the body. So it is interesting to keep an eye on research into the degree to which the brain can be induced to adapt to damage, to shift and repurpose neural networks to restore lost function. Here, researchers find that stimulating the hypothalamas can enable repurposing of the remaining connections in a damaged but not severed spinal cord.
A spinal cord injury (SCI) disrupts the neuronal projections from the brain to the region of the spinal cord that produces walking, leading to various degrees of paralysis. Here, we aimed to identify brain regions that steer the recovery of walking after incomplete SCI and that could be targeted to augment this recovery. To uncover these regions, we constructed a space-time brain-wide atlas of transcriptionally active and spinal cord-projecting neurons underlying the recovery of walking after incomplete SCI. Unexpectedly, interrogation of this atlas nominated the lateral hypothalamus (LH). We demonstrate that glutamatergic neurons located in the LH (LHVglut2) contribute to the recovery of walking after incomplete SCI and that augmenting their activity improves walking.
We translated this discovery into a deep brain stimulation therapy of the LH (DBSLH) that immediately augmented walking in mice and rats with SCI and durably increased recovery through the reorganization of residual lumbar-terminating projections from brainstem neurons. A pilot clinical study showed that DBSLH immediately improved walking in two participants with incomplete SCI and, in conjunction with rehabilitation, mediated functional recovery that persisted when DBSLH was turned off. There were no serious adverse events related to DBSLH. These results highlight the potential of targeting specific brain regions to maximize the engagement of spinal cord-projecting neurons in the recovery of neurological functions after SCI.
Link: https://doi.org/10.1038/s41591-024-03306-x
View the full article at FightAging
