Developmental Maturation of the Cerebellar White Matter-an Instructive Environment for Cerebellar Inhibitory Interneurons.

In the developing cerebellum, the nascent white matter (WM) serves as an instructive niche for cerebellar cortical inhibitory interneurons. As their Pax2 expressing precursors transit the emerging WM, their laminar fate is programmed. The source(s) and nature of the signals involved remain unknown. Here, we used immunocytochemistry to follow the cellular maturation of the murine cerebellar WM during this critical period. During the first few days of postnatal development, when most Pax2 expressing cells are formed and many of them reach the cerebellar gray matter, only microglial cells can be identified in the territories through which Pax2 cells migrate. From p4 onward, cells expressing the oligodendrocytic or astrocyte markers, CNP-1, MBP or GFAP, started to appear in the nascent WM. Expression of macroglial markers increased with cerebellar differentiation, yet deep nuclei remained GFAP-negative at all ages. The progressive spread of maturing glia did not correlate with the exit of Pax2 cells from the WM, as indicated by the extensive mingling of these cells up to p15. Whereas sonic hedgehog-associated p75NTR expression could be verified in granule cell precursors, postmitotic Pax2 cells are p75NTR negative at all ages analyzed. Thus, if Pax2 cells, like their precursors, are sensitive to sonic hedgehog, this does not affect their expression of p75NTR. Our findings document that subsequently generated sets of Pax2 expressing precursors of inhibitory cerebellar interneurons are confronted with a dynamically changing complement of cerebellar glia. The eventual identification of fate-defining pathways should profit from the covariation with glial maturation predicted by the present findings.

The Impact of Time to Initiate Therapeutic Hypothermia on Short-Term Neurological Outcomes in Neonates with Hypoxic-Ischemic Encephalopathy.

BACKGROUND: Therapeutic hypothermia is the standard treatment for neonates with hypoxic-ischemic encephalopathy. Preclinical evidence indicates that the time to initiate therapeutic hypothermia correlates with its therapeutic success. This study aims to explore whether there is a correlation between the early initiation of therapeutic hypothermia and improved short-term neurological outcomes in cooled asphyxiated newborns. METHODS: A retrospective analysis was conducted, involving 68 neonates from two different neonatal intensive care units. The impact of time to initiate treatment, time to reach the target temperature, and time between initiation and target temperature was correlated with short-term outcomes on MRI. RESULTS: We did not find a significant difference between outcomes regarding the time to start treatment and the time to achieve the target temperature. Interestingly, neonates with a poor outcome were treated on average earlier than neonates with a favorable outcome but required more time to reach the target temperature. Additionally, the study results did not support the hypothesis that a shorter time to initiate treatment would lead to shorter times to achieve the target temperature. CONCLUSION: Based on our findings, it is recommended to prioritize a thorough evaluation of neonatal encephalopathy before initiating therapeutic hypothermia. Early initiation of treatment should be balanced with the time required for precise assessment to ensure better outcomes.