Reduced post-stroke glial scarring in the infant primate brain reflects age-related differences in the regulation of astrogliosis

Replicating infant astrocyte behavior in the adult after brain injury improves outcomes

“…This trend was highlighted in a previous study in which we demonstrated that the intrinsic and extrinsic regulators or astrocyte reactivity differed between infants and adults marmoset monkeys [10,19]. This correlated to a smaller, more discrete chronic scarring which was more permissible to neuronal sparring after perinatal stroke compared to the equivalent injury in middle-aged adults [10].…”

“…EphA7 expression is primarily associated with neurons in both rodents and primates [30]. The reduction of EphA7 in infants without a similar occurrence in adults, where neuronal loss is more severe [10], most likely indicates neuronal downregulation of EphA7 expression in infants.…”

“…For example, limiting neuronal apoptosis, maintaining homeostasis and providing trophic support to surviving neurons [4][5][6]. Additionally, the capacity of reactive astrocytes to shift between states of reactivity, evidenced by changes in gene expression and function [7], demonstrates a high level of age-and environment-dependent plasticity [8][9][10][11] that drives the interplay between neuroprotective and neurotoxic roles. Indeed, evidence that the blockade of scar formation after spinal cord injury led to worse outcomes [12], indicates that the glial scar is, to an extent, required for CNS repair.…”

“…A wealth of evidence has linked these guidance cues with the pathophysiology and pathogenesis of CNS injury. Specifically, Eph/ ephrin signaling is a crucial regulator of astrocyte reactivity in rodents [20][21][22][23][24], nonhuman primates [10,25] and human [26]. Furthermore, the Eph/ ephrins have been the target of a number of preclinical treatment studies [27,28].…”

“…Furthermore, the Eph/ ephrins have been the target of a number of preclinical treatment studies [27,28]. The significant transcriptional differences between rodent and human astrocytes [29], as well as the more protracted pathophysiological time course in primates [10,19] were accounted for by using a clinically relevant model of perinatal and middle-aged focal ischemia in the marmoset monkey's primary visual cortex (V1) of [19].…”