Neonatal Cannabidiol Exposure Impairs Spatial Memory and Disrupts Neuronal Dendritic Morphology in Young Adult Rats.

Early life is a sensitive period for brain development. Perinatal exposure to cannabis is increasingly linked to disruption of neurodevelopment; however, research on the effects of cannabidiol (CBD) on the developing brain is scarce. In this study, we aim to study the developmental effects of neonatal CBD exposure on behavior and dendritic architecture in young adult rats.

Testosterone is Sufficient to Impart Susceptibility to Isoflurane Neurotoxicity in Female Neonatal Rats.

Background: Volatile anesthetic exposure during development leads to long-term cognitive deficits in rats which are dependent on age and sex. Female rats are protected relative to male rats for the same exposure on postnatal day 7. Here we test our hypothesis that androgens can modulate chloride cotransporter expression to alter the susceptibility to neurotoxicity from GABAergic drugs using female rats with exogenous testosterone exposure.

Androgenic Modulation of the Chloride Transporter NKCC1 Contributes to Age-dependent Isoflurane Neurotoxicity in Male Rats.

Background: Cognitive deficits after perinatal anesthetic exposure are well established outcomes in animal models. This vulnerability is sex-dependent and associated with expression levels of the chloride transporters NKCC1 and KCC2. The hypothesis was that androgen signaling, NKCC1 function, and the age of isoflurane exposure are critical for the manifestation of anesthetic neurotoxicity in male rats.

Functional Characterization of the Basal Amygdala-Dorsal BNST Pathway during Contextual Fear Conditioning.

Both the basal amygdala (BA) and the bed nucleus of the stria terminalis (BNST) can participate in contextual fear, but it is unclear whether contextual fear engrams involve a direct interaction between these two brain regions. To determine whether dorsal BNST (dBNST)-projecting neurons in the BA participate in contextual fear engrams, we combined the TetTag mouse with a retrograde tracer to label dBNST-projecting cells in the BA. We identified a population of neurons located in the anterior subdivision of the BA (aBA) that was activated during fear conditioning and reactivated during retrieval but that did not project to the dBNST.

Voluntary Exercise Rescues the Spatial Memory Deficit Associated With Early Life Isoflurane Exposure in Male Rats.

Background: Early life anesthesia exposure results in long-term cognitive deficits in rats. Environmental enrichment consisting of social housing, a stimulating environment, and voluntary exercise can rescue this deficit. We hypothesized that exercise alone is sufficient to rescue the cognitive deficit associated with perinatal anesthesia.

Anesthesia-induced Recognition Deficit Is Improved in Postnatally Gonadectomized Male Rats.

Background: Preclinical investigations of the effects of general anesthesia on the young brain show differences in vulnerability of males and females to anesthetic exposure at different times during development. However, the mechanism underlying this sex difference is poorly understood. Perinatal testosterone is the primary determinant of sexual differentiation and likely plays an important role in defining the period of susceptibility to anesthetic injury.

Female rats are more vulnerable to lasting cognitive impairment after isoflurane exposure on postnatal day 4 than 7.

Background: The factors determining peak susceptibility of the developing brain to anaesthetics are unclear. It is unknown why postnatal day 7 (P7) male rats are more vulnerable to anaesthesia-induced memory deficits than littermate females. Given the precocious development of certain regions in the female brain during the neonatal critical period, we hypothesised that females are susceptible to anaesthetic brain injury at an earlier time point than previously tested.

Histological and cognitive alterations in adult diabetic rats following an episode of juvenile diabetic ketoacidosis: Evidence of permanent cerebral injury.

Evidence suggests that diabetic ketoacidosis (DKA) may cause subtle cognitive alterations in children but the mechanisms are poorly understood. Acute DKA is associated with reactive astrogliosis and microglial activation in a rat model. Whether these inflammatory changes permanently alter brain histology is unknown.

Is a short anesthetic exposure in children safe? Time will tell: a focused commentary of the GAS and PANDA trials.

Early life exposure to general anesthesia in preclinical studies has consistently led to permanent cognitive deficits later in life. However, the extent to which this finding is translatable to humans is the subject of much debate as the results from clinical studies have been mixed. Recently two well-designed clinical trials have attempted to add clarity to our murky understanding.