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

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.

Regional differences in mitral cell development in mouse olfactory bulb.

Olfactory sensory neurons (OSNs) located in the dorsomedial and ventromedial regions of the olfactory epithelium (OE) are distinguished from one another based on their molecular expression patterns. This difference is reflected in the separation of the glomerular layer of the olfactory bulb (OB) into dorsomedial and ventrolateral regions. However, it is unclear whether a complementary separation is also evident in the projection neurons that innervate the OB glomeruli. In this study, we compared the development of the OB between different regions by focusing on the transcription factor, Tbx21, which is expressed by mitral and tufted cells in the mature OB. Examining the OB at different developmental ages, we found that Tbx21 expression commenced in the anteromedial region called the tongue-shaped area, followed by the dorsomedial and then ventrolateral areas. We also showed that the tongue-shaped area was innervated by the OSNs located in the most dorsomedial part of the ventrolateral OE, the V-zone:DM. Interestingly, the generation of OSNs occurred first in the dorsomedial zone including the V-zone:DM, suggesting a correlation between the time course of OSN generation in the OE and Tbx21 expression in their target region of the OB. In contrast, expression of vGluT1, which is also found in all mitral cells in the mature OB, was first detected in the ventrolateral region during development. Our findings demonstrate that the development of projection neurons occurs in a compartmentalized manner in the OB; tongue-shaped, dorsomedial, and ventrolateral areas, and that not all projection neurons follow the same developmental pathway.

Deep hypothermia reverses behavioral and histological alterations in a rat model of perinatal asphyxia.

The consequences of perinatal asphyxia (PA) include alterations which may manifest as schizophrenia. Characteristic features of this disease include a decrease in specific subpopulations of GABAergic cells and deterioration of social interaction. The purpose of this study is to assess if a deep and short-hypothermic treatment can ameliorate this damage in a model of PA. Rats offsprings were exposed to 19 min of asphyxia by immersing the uterus horns in water at 37 °C followed by 30 min in air at 10 °C that resulted in 15 °C body temperature. At postnatal day 36-38, the rats were tested in the open field and social interaction paradigms and processed for immunostaining of calbindin and reelin. A brief exposure to deep hypothermia reversed the deterioration produced by PA in play soliciting. PA decreased the density of calbindin neurons in layer II of the Anterior Insular Cortex, while deep hypothermia reversed this effect. Paradoxically, in AIC, there was a significant increase in the number of reelin-secreting neurons in layers II and III generated by PA and this increase was reversed by hypothermia. This suggests a compensatory mechanism, where reelin neurons trend to compensate for the loss of calbindin neurons, at least within Anterior Insular Cortex. Finally, the deep hypothermic shock might represent a valuable therapeutic alternative to treat PA.