Effect of grape seed extract on improving memory and learning impairment induced by streptozotocin in male rat

Background and Objective: Alzheimer's disease is an age-related disease that is characterized by dementia and loss of neurons in the brain. It has been shown that brain oxidative stress plays an important role in aging and neurodegenerative disorders. This study was done to evaluate the effect of grape seed extract [GSE] on memory impairment induced by intracerebroventricular [ICV] injection of streptozotocin [STZ] in animal model of Alzheimer's disease

Methods: In this experimental study, Eighty adult male Wistar rats were randomly allocated into control, sham, grape seed extract [100 mg/kg/bw, 30 days, orally] plus STZ and STZ plus grape seed extract. Animals memory were evaluated using Morris water maze, shuttle box and T maze tests

Results: Intracerebroventricular injection of STZ caused memory corruption in all tests. Administration of GSE before and after of administration of intracerebroventricular STZ in the Morris water maze test, significantly reduced latency to get to the hidden platform compared to Alzheimer's group [P<0.05]. The latency to enter the dark compartment in passive avoidance memory test significantly increased in compare to animal model of Alzheimer's disease [P<0.05]. The selection of the right arm of the T-maze test in animals that received grape seed extract before and after of STZ injection significantly increased compared to animal model of Alzheimer's disease [P<0.05]

Conclusion: Grape seed extract has important effect in prevention and improving memory impairment induced by intracerebventricular injection of STZ

[ role of proinflammatory cytokines in mediation of brain antiedema effect of female sex steroids following traumatic brain injury]

Background and Aims: Release of proinflammatory cytokines after traumatic brain injury [TBI] is a major cause of brain edema. Previous studies demonstrated that sex steroids decrease brain edema induced by TBI. In this study changes of brain cytokines after the administration of estrogen and progesterone 24 hours after TBI were evaluated. Materials and Methods: Female rats were divided into 7 groups. Groups 1 and 2 were considered as control and sham respectively and other 5 groups underwent bilateral ovariectomy and considered as vehicle, physiologic does of estrogen [E1], pharmacologic dose of estrogen [E2], physiologic dose of progesterone [P1] and pharmacologic dose of progesterone [P2]. Vehicle and sexual steroid hormones were injected intraperitoneally 30 minutes after TBI. Moderate TBI was induced by Marmarou method. Neurologic scores [VCS] were evaluated immediately, 1 h, 4 h and 24 h after TBI. Brain level of IL-1, IL-6, TNF-, TGFestrogen and progesterone were measured 24 hours after TBI by ELISA method

Results: E1 and E2 groups showed respectively 27.5% and 27% decrease in brain level of IL-1 compared to vehicle. Brain level of IL-1 increased in vehicle group compared to sham. E1 and P1 groups showed respectively 47% and 20.5% decrease of brain IL-6 level compared to vehicle. Brain Level of TNF- increased 48.5% in E2 group compared to the vehicle group. Both estrogen and progesterone in physiologic and pharmacologic doses increased TGF-, but the highest increase of TGF- level was about 9.5 times and was observed in E1 group. Brain level of -Estradiol increased 1.8 times in E2 group and progesterone increased 1.84 times in P2 group compared to the vehicle group. Veterinary coma scale [VCS] increased in E1, E2, P1 and P2 group at 1 hour after TBI, whereas, 4 h after TBI only in E1 and P1 and 24 h after TBI, in E1, E2 and P1 groups VCS, showed increase

Conclusion: Neuroprotective effect of sex hormones in reducing cerebral edema is probably performed by decrease of brain level of IL-1 and IL-6 and increase of brain level of TNF- and TGF- after TBI. Ke

Neuroprotection effect of female sex steroids after traumatic brain injury in rats: the role of inflammatory cytokines

Previous studies have demonstrated estrogen and progesterone decrease brain edema induced by TBI. The aim of the present study was to determine the effect of female sex steroids on cytokines, and proinflammatory evaluation of the effects of cerebral edema of these hormones whether ovarian hormones decrease brain edema by change in concentrations of proinflammatory cytokines. In this experimental study, 98 ovariectomized female rats [except groups 1 and 2] were divided into groups of control, sham, vehicle, low does of estrogen [El], high dose of estrogen [E2], low dose of progesterone [PI] and high dose of progesterone [P2]. Vehicle and sexual steroid hormones were injected intraperitoneally at 0.5 h after Moderate and diffuse TBI induced by Marmarou method. Brain level of cytokines and ovarian hormones were measured 6 h after TBI by ELISA method. Both E2 and PI caused significant increase of 52.8% and 79.2% in brain level of IL-lp. P2 significantly decreased the levels of IL-6 and TNF-alpha by 45.9% and 72% respectively. TGF-beta level seem to be increased by El up to 3.37 times significantly. Level of beta-Estradiol increased 4.58 times in E2 group and progesterone increased 1.56 times in P2 group significantly. This results suggested that ovarian hormones increased brain IL-lp and TGF-P and decreased IL-6 and TNF-alpha, this may be one mechanism by which hormones reduce cerebral edema

[Effect of short-term forced exercise on naloxone induced withdrawal symptoms in morphine addicted male rats]

Opioid dependence has been causing limitation in usage of morphine and other opioid drugs in pain control. The aim of this study was to assess the effect of short-term forced exercise on withdrawal syndrome in morphine addicted male rats. This experimental study was done in the physiology research center of Ahwas Jondishapour University of Medical Sciences. Twenty four young male Wistar rats, weighing 200-300gr, were randomly divided into four groups: no addiction and no exercise, no addiction and exercise, addiction and no exercise and addiction and exercise. The exercise groups underwent treadmill forced exercise for ten days. The first five days morphine was administrated [ip] twice daily with increasing dose [5, 10, 20, 40, 50 mg/kg] to addicted groups. Also single dose [50mg/kg] of morphine was administrated to them on the 10[th] day of exercise. After administration of naloxone hydrochloride the withdrawal symptoms were evaluated for 5 minutes. The findings of this study were analyzed by SPSS software and One- way ANOVA [Tukey] test. The findings of this study showed that the withdrawal symptoms was elevated in exercise and addicted groups in comparison with control group [p<0.05, p<0.01]. However, most of withdrawal symptoms decreased in addicted and exercise group in comparison with addicted and no exercise group [p<0.01, p<0.001]. The exercise could increase endogenous opioid and withdrawal symptoms in animals but reduce withdrawal symptoms in addicted and exercise groups compared to addicted and no exercise group. Its mechanism might be related to down regulation and low sensitivity of opioid receptors

[ effect of apple vinegar on blood glucose control and lipid profile in rats]

Regarding the recent evidence suggesting the effect of apple vinegar on reduction of postprandial blood glucose, this study was carried out with the aim of determining the effect of apple vinegar on fasting blood glucose, glycosylated hemoglobin [HbA1c], and lipid profile in healthy and diabetic rats. 31 wistar male rats were assigned into 4 groups as follows: the healthy control, apple vinegar-fed healthy, diabetic control, and apple vinegar-fed diabetics. Streptozotocin was used to induce diabetes in rats. The control groups received standard rat food, while the treatment groups received mixed 6% apple vinegar and standard rat food for 4 weeks. Fasting blood glucose, HbA[1c] and lipid profile [total cholesterol [TC], triglyceride [TG], LDL cholesterol, HDL cholesterol] were measured before and after the intervention. Fasting blood glucose did not change with the consumption of apple vinegar. However, HbA[1c] in diabetic group decreased significantly compared with pre-intervention [P<0.05] and control-diabetic group [P<0.05]. In healthy group with the uptake of apple vinegar, reduction of LDL [P<0.005], and increase of HDL [P<0.005] were observed compared to pre-intervention and with healthy control. In diabetic group with the uptake of apple vinegar significant reduction of TG [P<0.005] and significant increase of HDL [P<0.05] were observed compared to the control group. The results of this study showed that uptake of apple vinegar improve lipid profile in healthy and diabetic rats, and reduces HbA1c in diabetic rats

[ effect of white vinegar on fasting blood glucose, glycosylated hemoglobin and lipid profile in normal and diabetic rats]

There is evidence suggesting a lowering effect for vinegar on postprandial blood glucose concentrations. This study aimed at evaluating the effect of vinegar on fasting blood glucose, glycosylated hemoglobin [HbA1c] and lipid profiles in healthy and diabetic rats. Male wistar rats were divided into four groups: the healthy control, healthy fed with white vinegar, diabetic control, and diabetic fed with white vinegar, groups. To induct diabetes, Streptozotocin was used. For a period of 4 weeks the control groups received standard food and the treatment groups received white vinegar-mixed pelleted food [6%]. Fasting blood glucose, HbA1c and lipid profiles were measured before and after intervention. White vinegar had no significant effect on fasting blood glucose and HbA1c in either the healthy or diabetic group. Statistical analysis of data showed that in the healthy group fed white vinegar there was a significant decrease in LDL-cholestrol [LDL-C] and a significant increase in HDL-cholestrol [HDLC]. Also, there was a significant increase in HDL-C compared with healthy control group. White vinegar reduced TG/LDL-C and HDL-C/LDL-C ratios in healthy rats, 44.5% and 25.8%, respectively. The diabetic control group showed a significant increase in triglyceride [TG] along with a significant decrease in HDL-C. However, the diabetic group fed with white vinegar showed a significant decrease in TG compared to the control diabetic group. TG/LDL-C and HDL-C/LDL-C ratios increased in diabetic control group but not in the diabetic group fed white vinegar. The results of this study clearly indicate that consumption of white vinegar for four weeks could have significant favorable effects on the lipid profiles of healthy and diabetic rats

[ effect of intrafrontal cortex injection of physostigmine on active avoidance learning on the animal model of Alzheimer's disease]

Cholinergic neurons of nucleus basalis magnocellularis [NBM] have a key role in learning and memory process. It has been shown that these neurons are degenerated in patients with Alzheimer disease [AD]. On the other hand, using the cholinomimetic agents and acetylcholinesterase inhibitors improve cognition in these patients. Some studies have shown that the frontal cortex receives some cholinergic projections from NBM. In the present study, the effect of intrafrontal cortex administration of physostigmine [acetylcholinesterase inhibitor] was investigated on active avoidance learning on the animal model of AD. In this experimental study, NBM was lesioned electricaly in Wistar male rats, [250-300g body weight] for making the animal model of AD. Because the frontal cortex receives cholinergic projections from NBM, different doses of physostigmine [2.5, 5, 7.5 microg/microl] were injected bilaterally into the frontal cortex of lesioned rats 20 minutes before active avoidance learning [8 sessions, 30 steps in each session] in Y-maze. The results showned that active avoidance learning was decreased significantly in NBM-lesioned group. Also intrafrontal cortex injection of phsostigmine [2.5, 5, and 7.5 microg/microl] significantly severed NBM lesion-induced learning deficiency. The findings of this study suggest that the cholinergic projection of NBM to frontal cortex in lesioned animals has a negative role on this type of learning. It seems that other neurotransmitter systems such as glutamate and other afferent projections from different brain areas to frontal cortex probably are involved in this phenomenon

[Effects of intramedial septum infusion of physostigmine on hippocamal EEG and spatial memory in animal model of Alzheimer's disease]

The basalis magnocellularis nucleus [NBM] cholinergic projections to amygdala and forntal cortex have a crucial role in spatial learning and memory. There are relations between septum, hippocampus, amygdala and cerebral cortex. The role of NBM cholinergic projections to medial septum and then to hippocampus on spatial learning and memory, hippocamal EEG in animal model of Alzheimer's disease was assessed after unilateral lesion of NBM with phtalic acid [300 ng/kg]. Physostigmine was infused into the medial septum. Forty wistar male rats were divided in 4 groups: control, lesioned, lesioned received saline and lesioned treated with physostigmine [5microg/microl]. Animals were operated stereotaxicaly for NBM lesioning, intramedial septum cannulation and hippocamal electrode implantation. Rats were trained one session daily into T-maze and alterations of hippocampal EEG amplitude were evaluated. The results showed intramedial septum infusion of physostigmine improves spatial learning and memory in lesioned animals significantly [p<0.01]. NBM cholinergic projections to medial septum and then the hippocampus as well as its projections to amygdala and cortex have a role in spatial learning and memory. Administration of physostigmine improves decrease of hippocampal EEG amplitiude, spatial learning and memory impairment that was induced by NMB lesioning in male rats

[ effect of reversible anesthesia of nucleus paragigantocellularis [PGi] on local EEG amplitude of locus coeruleus [LC] nucleus during opiate-withdrawal in rats]

Since several evidences exist that the nucleus paragigantocellularis [PGi], located in the rostral ventrolateral medulla, is one of the major afferent to the nucleus locus coeruleus [LC], in this study the effect of reversible anesthesia of PGi nucleus with 4% lidocaine [0.5microl/rat] on local EEG amplitude of LC and behavioral signs of morphine-induced witdrawal was investigated. The local EEG amplitude of LC nucleus was significantly decreased by administration of lidocaine in control and morphine-dependent rats. Also, in LC nucleus of morphine-dependent rats, the amplitude and behavioral signs increased significantly following administration of naloxone [10mg/kg; s.c.]. In addition, microinjection of lidocaine into the PGi before administration of naloxone reversed the local EEG amplitude of LC to the amount of controls and decreased the behavioral signs of withdrawal syndrome, significantly. There was no significant change in the amplitude in morphine-dependent rat after chronic exposure to morphine than before. These results indicated that during withdrawal syndrome, activation of LC neurons and behavioral signs of it likely arise from PGi nucleus and are mediated by LC neurons. In addition, no changes in the amplitude of LC and/ or elsewhere were appeared in LC activity. The findings are consistent with the hypothesis that during morphine withdrawal, there is an increased in unit activity of the PGi afferents to the LC or an increased release of excitatory transmitter from their terminals in the LC