Downregulated hippocampal expression of brain derived neurotrophic factor and tyrosine kinase B in a rat model of comorbid epilepsy and depression.

OBJECTIVE:  To investigate the expression of brain-derived neurotrophic factor(BDNF) and tyrosine kinase B (TrkB) protein in the hippocampus of model rats of comorbid epilepsy and depression. METHODS: A rat model of epilepsy was established using lithium chloride.pilocarpine. Among these epileptic rats, those with comorbid depression were selected by a battery of behavioral tests starting on the 14th day after establishing the epilepsy model. A depression group was established by unpredicted chronic mild stress (UCMS) and separate housing. These treatment groups were compared to an untreated control group. Thirteen rats per group were examined by immunofluorescence staining with optical density quantitation to determine the distribution of BDNF- and TrkB-positive cells in the hippocampus and by western blotting to estimate total protein expression levels during the 4th week after establishing the models. Immunofluorescence staining for NeuN was also conducted in hippocampus to evaluate neuronal survival. Depression-like behaviors were also assessed. RESULTS:  Compared to the untreated control group and the epilepsy alone group, the comorbid group exhibited lower average optical densities of BDNF- and TrkB-immunopositive cells as well as lower total BDNF and TrkB protein expression levels (all P = 0.000). The comorbid group exhibited lower behavioral scores compared to all other groups (all P=0.000). Numbers of NeuN-positive cells were lower in the hippocampus of all three experimental groups compared to the untreated control group (all P = 0.000). CONCLUSIONS:  These results suggest that hypofunctional BDNF-TrkB signaling may contribute to depression in epilepsy. ABBREVIATIONS: BDNF: Brain-derived neurotrophic factor; TrkB: tyrosine kinase B; UCMS: unpredicted chronic mild stress; PBS: phosphate-buffered saline; HS: Hippocampal sclerosis.

Mannitol improves cerebral oxygen content and postoperative recovery after prolonged retroperitoneal laparoscopy.

BACKGROUND: Prolonged pneumoperitoneum has cerebral adverse effects that may delay recovery and cause postoperative cognitive changes. The purpose of this study was to investigate the effect of mannitol infusion after pneumoperitoneum initiation on cerebral oxygen balance and quality of postoperative recovery in patients undergoing prolonged retroperitoneal laparoscopy. METHODS: Forty patients scheduled for retroperitoneal laparoscopic radical excision of prostatic carcinoma were randomly divided into two groups (n = 20, each) to receive either 0.5 g/kg of 20% mannitol 150 min after the initiation of pneumoperitoneum or an equal volume of 0.9% normal saline. After surgery, time to extubation and recovery time were recorded. The Observer's Assessment of Alertness/Sedation (OAA/S) scale was used to assess the quality of recovery. The Mini-Mental State Exam (MMSE) was given to test cognitive function preoperatively and at 1, 2, and 3 h after extubation. Blood samples from the jugular bulb and the radial artery were collected for blood gas analysis before CO2 insufflation and at 10, 60, and 180 min after insufflation. RESULTS: In the control group (without mannitol), the difference between arterial and venous oxygen content (CaO2-CvO2) before insufflation (6.21 ± 2.58 mL/dL) was significantly greater than it was 3 h after insufflation (2.63 ± 1.29 mL/dL; p < 0.05). Furthermore, 3 h after insufflation, the CaO2-CvO2 also was higher in the group that had been administered mannitol (5.93 ± 1.98 mL/dL) than it was in the control group at that time (p < 0.05). Lactic acid in both arterial and jugular venous blood of the control group at 3 h postinsufflation (2.39 ± 0.89 and 2.51 ± 0.72 mg/dL, respectively) had increased significantly from the preinsufflation values (1.18 ± 0.82 and 1.1 ± 0.85 mg/dL). In the group that received mannitol, the lactic acid levels 3 h postinsufflation were essentially the same as the preinsufflation values. The recovery and extubation times in those receiving mannitol (12.19 ± 2.12 and 20.14 ± 3.62 min, respectively) were significantly shorter than in the control group (21.25 ± 3.61 and 28.79 ± 4.73 min; p < 0.05). The OAAS scores of the mannitol group at the time of extubation and 10 min afterward was significantly higher than these scores in the control group (p < 0.05). One hour and 2 h after extubation, the cognitive function score of the mannitol group was significantly higher than for the control group (p < 0.05). CONCLUSIONS: After prolonged retroperitoneal laparoscopy, there is an imbalance between oxygen supply and demand. A small dose of mannitol can effectively improve cerebral oxygen metabolism, recovery, and cognitive function after the operation.