Gallic acid improves cognitive, hippocampal long-term potentiation deficits and brain damage induced by chronic cerebral hypoperfusion in rats.

Abstract: Cerebral Hypoperfusion Ischemia (CHI) has important role in neuronal damage and behavioral deficits, including memory and Long-term Potentiation (LTP) impairment. Protective effects of Gallic Acid (GA) on memory, hippocampus LTP and cell viability were examined in permanent bilateral common carotid artery occlusion in rats. Animals were divided into 9 groups: Control (Cont); sham operated (Sho); Cerebral Hypoperfusion Ischemia (CHI); CHI received normal saline (CHI +Veh); CHI treated with different doses gallic acid (50, 100, 200 mg kg(-1) for 5 days before and 5 days after CHI induction, orally); CHI treated with phenytoin (50 mg kg(-1), ip) (CHI+Phe); and sham operated received 100 mg kg(-1), orally (Sho+GA100). CHI was induced by bilateral common carotid artery occlusion (2VO). Behavioral, electrophysiological and histological evaluations were performed. Data were analyzed by one-way and repeated measures ANOVA followed by tukey's post-hoc test. GA improved passive avoidance memory, hippocampal LTP and cell. viability in hippocampus and cortex of ischemic rats significantly (p < 0.01). The results suggest that gallic acid via its antioxidative and free radicals scavenging properties attenuates CHI induced behavioral and electrophysiological deficits and has significant protective effect on brain cell viability. Dose of 100 mg kg(-1) GA has affected the ischemic but not intact rats and its effect was more potent significantly than phenytoin, a routine drug for ischemic subjects.

Protective effects of oral crocin against intracerebroventricular streptozotocin-induced spatial memory deficit and oxidative stress in rats.

Intracerebroventricular (ICV) streptozotocin (STZ) has been shown to cause cognitive impairment, associated with free radical generation. In this study, we evaluated the effects of crocin on cognitive performance in ICV STZ-lesioned rats (3 mg/kg bilaterally, on day 1 and 3). Crocin (100 mg/kg, p.o.) was administered for 21 consecutive days, starting 1h prior to the first dose of STZ. Cognitive performance was assessed using Morris water maze task while the parameters of oxidative stress assessed, were malondialdehyde (MDA) and total thiol levels besides glutathione peroxidase (GPx) activity. STZ-lesioned rats showed a severe deficit in memory associated with elevated MDA levels, reduced GPx activity and total thiol content. Crocin treatment improved cognitive performance and resulted in a significant reduction in MDA levels and elevation in total thiol content and GPx activity. This study demonstrates that crocin may have beneficial effects in the treatment of neurodegenerative disorders such as Alzheimer's disease.

The effect of peripheral administration of growth hormone on AD-like cognitive deficiency in NBM-lesioned rats.

This study aimed to evaluate the peripheral administration of growth hormone (GH) on AD-like cognitive deficiency in NBM-lesioned rats induced by ibotenic acid (5 microg/microl, in each side). Forty-eight male Wistar rats (20-24 months old; weighing 330+/-30 g) randomly divided into six groups (n=8). The groups include control group, which were intact rats; n-L+GH group: non-lesioned rats with GH treatment (1mg/kg, 9.00 am, for 10 consecutive days); n-L+Veh group: non-lesioned rats with vehicle treatment; L group: NBM-lesioned rats; L+GH group: NBM-lesioned rats with GH treatment and L+Veh group: NBM-lesioned rats with same volume of vehicle treatment. Peripheral administration of GH in control had no effect on learning and memory, while in L+GH group produced a significant enhancement in spatial learning and memory comparing to L and L+Veh groups. The percent of time spent in goal quarter during probe trial has decreased significantly in L and L+Veh groups compared to n-L groups. While it has increased significantly in L+GH group compared to L and L+Veh groups. No significant difference in percent of time spent was seen between the control and n-L groups. The GH has known as a mediate that effect through IGF-1. As the IGF-1 itself is earlier shown to improve cognitive function it is likely that the observed effect of GH is mediated through release of IGF-1 from peripheral tissue into the circulation for further transport across the BBB. This mechanism may result in the improvement of learning and memory in rats with NBM lesion.

The effect of intra-hippocampal injection of growth hormone on spatial learning and memory in animal model of Alzheimer's disease.

The aim of this study was to evaluate the effect of intra-hippocampal injection of Growth Hormone (GH) on impaired spatial cognition in rats with Alzheimer's Disease (AD). Growth hormone replacement therapy leading to improved cognition and well-being has mainly been carried in GH-deficient patients. Nevertheless, relatively only a few studies have investigated the function of GH in the brain. Aged Wistar male rats (350-400 g, 18-20 months old) were randomly divided into 6 groups (7 in each): Control (healthy aged); L; L + Veh; L + GH10; L + GH20 and L + GH40. Rats with AD-like cognitive deficiency was induced by injection of ibotenic acid into Nucleus Basalis of Meynert (NBM) bilaterally (5 microg 0.5 microL(-1), each side). A guide cannula was implanted in the right hippocampus under stereotaxic surgery for injection of human recombinant GH (10, 20 and 40 microg 2 microL(-1), during 5 min, twice daily, 9:00 am and 3:00 pm, for 7 days). All rats were trained in Morris water maze to evaluate the spatial learning and memory. Escape latency, traveled distance to find hidden platform and percent time spent in gaol qudrant did not differ between L and L + Veh groups, while latency and distance were reduced significantly. But percent time spent in gaol quadrant (without hidden platform) was increased significantly in NBM-lesioned rats treated with GH (L + GH groups) dose dependently to compare with vehicle treated group. These results suggest that intra-hippocampal injection of GH to aged rats with dementia type of AD (with NBM lesioned) could improve spatial cognition.

Antiulcerogenic effect of Securigera securidaca L. seed extract on various experimental gastric ulcer models in rats.

Securigera securidaca belongs to the family Fabaceae is used in Iranian folk medicine to treat gastric disturbances. The present study was undertaken to evaluate the Securigera securidaca seed hydroalcoholic extract (SSE) and its subfractions for their gastroprotective effect in rat. Acute gastric ulceration in rats was produced by oral administration of ethanol (100%; 1 mL/200 g of body weight) or water immersion restraint-stress (5 h, water immersion restraint stress at 20-22 degrees C). Ranitidine (100 mg kg(-1), p.o.) was used as the reference antiulcer drug. After ethanol administration, the gastric wall mucus was examined. Chronic gastric ulceration was produced by injection of acetic acid in rat gastric subserosa. The antisecretory effect of the extract and its subfractions (ethyl acetate, chloroform and aqueous fractions) were investigated in pylorus-ligated rats. Administration of SSE significantly inhibited gastric mucosa damage induced by ethanol, water immersion restraint-stress and acetic acid in a dose-dependent manner. In pylorus ligature rats, SSE and its subfractions significantly reduced the basal gastric acid secretion and total acidity; moreover, it inhibited the increase in total acidity induced by carbachol. However, the antisecretory effect of the chloroform fraction was more potent than two other fractions. Administration of SSE did not affect the gastric mucus production. The results obtained in the present study indicate that the SSE has gastroprotective and antisecretory effects on gastric mucosa in rats.