Long-term prenatal stress increases susceptibility of N-methyl-D-aspartic acid-induced spasms in infant rats / 소아과

PURPOSE: Infantile spasms, also known as West syndrome, is an age-specific epileptic seizure. Most patients with this condition also exhibit delayed development. This study aimed to determine the effect of long-term prenatal stress on susceptibility to infantile spasms. METHODS: We subjected pregnant rats to acute or chronic immobilization stress. Resulting offspring received N-methyl-D-aspartic acid (15 mg/kg, intraperitoneally) on postnatal day 15, and their behaviors were observed 75 minutes after injection. The expression of KCC2 and GAD67 was also determined using immunohistochemistry. RESULTS: Exposure to long-term prenatal stress increased the frequency of spasms and decreased the latency to onset of spasms compared with offspring exposed to short-term prenatal stress. Expression of KCC2 and GAD67 also decreased in the group exposed to long-term prenatal stress compared with the group exposed to short-term prenatal stress. CONCLUSION: Our study suggests that exposure to long-term prenatal stress results in increased susceptibility to seizures.

Effects of propofol post-conditioning on hippocampal neuronal K+-Cl-co-transporter 2 expression in rats with cerebral ischemia/reperfusion injury / 中华麻醉学杂志

Objective To evaluate the effect of propofol post-conditioning on hippocampal neuronal K+-Cl-co-transporter 2 (KCC2) expression in the rats with cerebral ischemia/reperfusion (I/R) injury.Methods Seventy-two male Sprague-Dawley rats,aged 7-8 weeks,weighing 250-280 g,were randomly divided into 3 groups (n =24 each):sham operation group (group S),cerebral I/R (group I/R) and propofol post-conditioning group (group PP).The model of focal cerebral I/R injury was established by occlusion of the right middle cerebral artery.Propofol 20 mg· kg-1 · h-1 was infused over 2 h starting from the onset of reperfusion through the femoral vein in group PP.The equal volume of normal saline was given in S and I/R groups.Modified neurological severity score (mNSS) was used to evaluate the impairment of neurological function.The animals were then sacrificed and brains were removed for determination of the number of neurons (by Nissl' s staining) and expression of KCC2 (by immunofluorescence and Western blot) in hippocampal CA3 region.Results Compared with group S,the scores of mNSS were significantly increased,and the number of neurons and expression of KCC2 in hippocampal CA3 region were decreased in I/R group,and mNSS scores were increased,and no significant changes were found in the other parameters in group PP.Compared with group I/R,the mNSS scores were significantly decreased,and the number of neurons and expression of KCC2 in hippocampal CA3 region were increased in group PP.Conclusion The mechanism by which propofol post-conditioning reduces cerebral I/R injury is related to up-regulated expression of hippocampal KCC2 in rats.

Effect of sevoflurane on renal ischemia-reperfusion injury in rats and the role of Na+-2Cl--K+ cotransporter 1 and aquaporin 2 in it / 中华麻醉学杂志

Objective To investigate the effects of sevoflurane on renal ischemia-reperfusion (I/R) injury in rats and the role of Na+-2Cl--K+ cotransporter 1 (BSC1) and aquaporin 2 (AQP2) in it.Methods Twentyfour male Sprague-Dawley rats,aged 8-12 weeks,weighing 125-145 g,were randomly divided into 3 groups (n =8 each) ∶ sham operation group (S group),I/R group and sevoflurane group (Sev group).Renal ischemia was induced by occlusion of the renal artery for 45 min with atraumatic microclips followed by 24 h reperfusion.In group Sev,the rats inhaled 1 MAC (2.2％) sevoflurane,renal ischemia was induced after loss of consciousness and 1 MAC (2.2％) sevoflurane was inhaled for 1 h.The urine were collected at 24 h before I/R (T1) and 24 h of reperfusion (T2) for detection of urine specific gravity and creatinine (Cr) level.The urine volume was recorded.The endogenous creatinine clearance rate (Ccr) was calculated.Blood samples were taken from the irferior vena cava at T2 for determination of concentrations of serum blood urea nitrogen (BUN) and Cr and activities of superoxide dismutase (SOD) and myeloperoxidase (MPO),malondialdehyde (MDA) concentration.The left kidney was removed for determination of MPO and SOD activities and MDA content and for microscopic examination and the pathological changes of the renal tubule were scored.The expression of AQP2 and BSC1 was detected by immunohistochemistry and Western blot.Results Compared with group S,the urine volume was enlarged,concentrations of serum BUN and Cr were significantly increased,urine specific gravity and Ccr were significantly decreased,MPO and MDA levels were significantly increased,SOD activity was significantly decreased,the pathological score was significantly increased,and the expression of AQP2 and BSC1 was down-regulated in groups I/R and Sev (P ＜ 0.05).Cer was significantly higher,conceutratious of serum BUN and Cr and MPO and MDA levels were lower,SOD activity was higher,the pathological score was lower,and the expression of AQP2 and BSC1 was higher in group Sev than in group I/R (P ＜ 0.05).Sevoflurane inhalation significantly attenuated the pathological changes.Conclusion Sevoflurane can attenuate renal I/R injury in rats through up-regulating the expression of BSC1 and AQP2.

Water and Sodium Regulation in Heart Failure

Heart failure is the pathophysiological state characterized by ventricular dysfunction and associated clinical symptoms. Decreased cardiac output or peripheral vascular resistance lead to arterial underfilling. That is an important signal which triggers multiple neurohormonal systems to maintain adequate arterial pressure and peripheral perfusion of the vital organs. The kidney is the principal organ affected when cardiac output declines. Alterations of hemodynamics and neurohormonal systems in heart failure result in renal sodium and water retention. Activation of sympathetic nervous system, renin-angiotensin-aldosterone system and non-osmotic vasopressin release stimulate the renal tubular reabsorption of sodium and water. Dysregulation of aquaporin-2 and sodium transporters also play an important role in the pathogenesis of renal sodium and water retention.

Altered Regulation of Renal Sodium Transporters in Salt-Sensitive Hypertensive Rats Induced by Uninephrectomy

Uninephrectomy (uNx) in young rats causes salt-sensitive hypertension (SSH). Alterations of sodium handling in residual nephrons may play a role in the pathogenesis. Therefore, we evaluated the adaptive alterations of renal sodium transporters according to salt intake in uNx-SSH rats. uNx or sham operations were performed in male Sprague-Dawley rats, and normal-salt diet was fed for 4 weeks. Four experimental groups were used: sham-operated rats raised on a high-salt diet for 2 weeks (CHH) or on a low-salt diet for 1 week after 1 week's high-salt diet (CHL) and uNx rats fed on the same diet (NHH, NHL) as the sham-operated rats were fed. Expression of major renal sodium transporters were determined by semiquantitative immunoblotting. Systolic blood pressure was increased in NHH and NHL groups, compared with CHH and CHL, respectively. Protein abundances of Na+/K+/2Cl- cotransporter (NKCC2) and Na+/Cl- cotransporter (NCC) in the CHH group were lower than the CHL group. Expression of epithelial sodium channel (ENaC)-gamma increased in the CHH group. In contrast, expressions of NKCC2 and NCC in the NHH group didn't show any significant alterations, compared to the NHL group. Expressions of ENaC-alpha and ENaC-beta in the NHH group were higher than the CHH group. Adaptive alterations of NKCC2 and NCC to changes of salt intake were different in the uNx group, and changes in ENaC-alpha and ENaC-beta were also different. These altered regulations of sodium transporters may be involved in the pathogenesis of SSH in the uNx rat model.