Electrophysiological and inflammatory changes of CA1 area in male rats exposed to acute kidney injury: Neuroprotective effects of erythropoietin.

The high mortality rate associated with acute kidney injury (AKI) is commonly due to progressive, inflammatory multiple organ dysfunction, which often involves neurological complications. The AKI-stimulated mechanisms leading to brain dysfunction are not well understood, which hinders development of new therapeutic avenues to minimize AKI-mediated neural effects. The hippocampal CA1 area is a particularly vulnerable region during AKI but the electrophysiological and inflammatory mechanisms involved in this vulnerability remain largely unknown. Here, we used immunohistochemistry to quantitatively investigate the number of astrocytes expressing glial fibrillary acidic protein (GFAP) as an indicator of inflammation, and whole cell patch clamp to evaluate electrophysiological changes in CA1 at different time points following induction of bilateral renal ischemia (BRI) in male Wistar rats. Further we evaluated the effectiveness of erythropoietin (EPO, 1000 U/kg i.p.) in mitigating BRI-associated changes. Plasma concentrations of blood urea nitrogen (BUN) were significantly enhanced at 24 h, 72 h and 1 week, and creatinine (Cr) was increased at 24 h after reperfusion, which were changes reduced by EPO. BRI led to an increase in CA1 GFAP-positive cells 24 h and 72 h, but not 1 week, after reperfusion, and EPO reversed this effect of BRI at 24 h. Additionally, BRI caused an increase in the peak amplitude and coefficient of variation of CA1 pyramidal neuronal action potentials, which were changes not seen in presence of EPO. When taken together, altered neuronal electrophysiological properties and astrogliosis could contribute to the neurological complications induced by AKI, and EPO offers hope as a potential neuroprotective agent.

Early enriched environment prevents cognitive impairment in an animal model of schizophrenia induced by MK-801: Role of hippocampal BDNF.

Early life experience has long-lasting effects on brain and behaviour. This study aims to investigate the long-term effects of enriched environment (EE), which was imposed during the animals' development, on their recognition memory as well as hippocampal levels of brain-derived neurotrophic factor (BDNF), in an animal model of schizophrenia induced by chronic postnatal administration of MK-801. Forty male and female rat pups were separated in four distinct groups for each sex (n = 10). The rats were injected with MK-801 (1 mg/kg) or saline (1 cc/kg) on their postnatal days (P) 6-10. MK-801 and Control rats were maintained in standard or enriched cages (containing toys, tunnels, running wheels, and climbing frame), from their birth up to the time of behavioral experiments at P60. Neonatal challenge with MK-801 significantly impaired novel object recognition (NOR) in both male and female animals. EE exposure reversed the recognition memory only in male rats. MK-801 resulted in decreased levels of BDNF in the hippocampus, and EE exposure restored the decreased level. Our results provide evidence that BDNF plays an important role in pathophysiology of schizophrenia in the present animal model, and is a possible mechanism through which early EE can enhance the cognitive functions.