Deep hypothermia prevents striatal alterations produced by perinatal asphyxia: Implications for the prevention of dyskinesia and psychosis

Abstract

GABAergic medium spiny neurons are the main neuronal population in the striatum. Calbindin is preferentially expressed in medium spiny neurons involved in the indirect pathway. The aim of the present work is to analyze the effect of perinatal asphyxia on different subpopulations of GABAergic neurons in the striatum and to assess the outcome of deep therapeutic hypothermia. The uterus of pregnant rats was removed by cesarean section and the fetuses were exposed to hypoxia by immersion in water (19 min) at 37°C (perinatal asphyxia). The hypothermic group was exposed to 10°C during 30 min after perinatal asphyxia. The rats were euthanized at the age of one month (adolescent/adult rats), their brains were dissected out and coronal sections were immunolabeled for calbindin, calretinin, NeuN, and reelin. Reelin+ cells showed no staining in the striatum besides subventricular zone. The perinatal asphyxia (PA) group showed a significant decrease in calbindin neurons and a paradoxical increase in neurons estimated by NeuN staining. Moreover, calretinin+ cells, a specific subpopulation of GABAergic neurons, showed an increase caused by PA. Deep hypothermia reversed most of these alterations probably by protecting calbindin neurons. Similarly, there was a reduction of the diameter of the anterior commissure produced by the asphyxia that was prevented by hypothermic treatment.

Transition to extrauterine life and the modeling of perinatal asphyxia in rats

“…After a hysterectomy, full-term fetuses inside the uterus are immersed in water at 37 for periods of time that usually range from 15 to 21 min. Within this model, the most rigorous methodology involves including controls born by cesarean section and allowing one offspring to born by vaginal delivery to ensure fullterm gestation (Driscoll et al, 2018;Loidl et al, 1994;V azquez-Borsetti et al, 2016V azquez-Borsetti et al, , 2019V azquez-Borsetti et al, , 2020.…”

“…At PND0 is common to observe a paradoxical increase in specific GABAergic subpopulations produced by PA. GABAergic neurons with reelin and/or calretinin increase their density in response to the insult (Vázquez‐Borsetti et al, 2020). Also, an increase of cells with reelin has been observed in the anterior insular cortex.…”

“…These markers are co‐expressed in the cortex but not in the adult striatum. In this structure PA produced an increase in calretinin density (Vázquez‐Borsetti et al, 2020; Yang et al, 2008).…”

“…Glutamatergic transmission is more active, and the damage involves more neurons at PND7+. For example, using the delayed model, several works reported the loss of neurons as a decrease in NeuN‐positive cells (Ness et al, 2008; T. Wood et al, 2016), while in the models at PND0, there were no changes or even was observed an increase in the density of NeuN+ cells (Vázquez‐Borsetti et al, 2016, 2020).…”