Rat Model Of Carotid Artery Occlusion Research Articles

Neuroprotective Effects of Theobromine in permanent bilateral common carotid artery occlusion rat model of cerebral hypoperfusion.

Cerebral hypoperfusion (CH) is a common underlying mechanism of dementia disorders linked to aberrations in the neurovascular unit. Hemodynamic disturbances adversely affect cellular energy homeostasis that triggers a sequence of events leading to irrevocable damage to the brain and neurobehavioral discrepancies. Theobromine is a common ingredient of many natural foods consumed by a large population worldwide. Theobromine has shown health benefits in several studies, attributed to regulation of calcium homeostasis, phosphodiesterase, neurotransmission, and neurotrophins. The current study evaluated the neuroprotective potential of theobromine against CH in the permanent bilateral common carotid artery occlusion (BCCAO) prototype. Wistar rats were distributed in Sham-operated (S), S + T100, CH, CH + T50, and CH + T100 groups. Animals received permanent BCCAO or Sham treatment on day 1. Theobromine (50, 100mg/kg) was given orally in animals subjected to BCCAO for 14 days daily. CH caused neurological deficits (12-point scale), motor dysfunction, and memory impairment in rats. Treatment with theobromine significantly attenuated neurological deficits and improved sensorimotor functions and memory in rats with CH. In biochemistry investigation of the entire brain, findings disclosed reduction in brain oxidative stress, inflammatory intermediaries (tumor necrosis factor-α, interleukin-1β and - 6, nuclear factor-κB), markers of cell demise (lactate dehydrogenase, caspase-3), acetylcholinesterase activity, and improvement in γ-aminobutyric acid quantity in rats that were given theobromine for 14 days daily after CH. Histopathological analysis substantiated attenuation of neurodegenerative changes by theobromine. The findings of this study indicated that theobromine could improve neurological scores, sensorimotor abilities, and memory in CH prototype.

Ligustilide ameliorates cognitive impairment via AMPK/SIRT1 pathway in vascular dementia rat.

Vascular dementia (VaD) is the second cause of dementia after Alzheimer's disease. Ligustilide (LIG) is one of the main active ingredients of traditional Chinese medicines, such as Angelica. Studies have reported that LIG could protect against VaD. However, the mechanism is still confused. In this study, we employed a bilateral common carotid artery occlusion rat model to study. LIG (20 or 40mg/kg/day) and Nimodipine (20mg/kg) were orally administered to the VaD rats for four weeks. Morris water maze test showed that LIG effectively ameliorated learning and memory impairment in VaD rats. LIG obviously reduced neuronal oxidative stress damage and the level of homocysteine in the brain of VaD rats. Western blot results showed that pro-apoptotic protein Bax and cleaved caspase 3 increased and anti-apoptotic protein Bcl-2 decreased in the hippocampi of VaD rats. But after LIG treatment, these changes were reversed. Moreover, Nissl staining result showed that LIG could reduce neuronal degeneration in VaD rats. Furthermore, LIG enhanced the expressions of P-AMPK and Sirtuin1(SIRT1) in VaD rats. In conclusion, these studies indicated that LIG could ameliorate cognitive impairment in VaD rats, which might be related to AMPK/SIRT1 pathway activation.

Anti-inflammatory efficacy of Berberine Nanomicelle for improvement of cerebral ischemia: formulation, characterization and evaluation in bilateral common carotid artery occlusion rat model

BackgroundBerberine (BBR) is a plant alkaloid that possesses anti-inflammatory and anti-oxidant effects with low oral bioavailability. In this study, micelle formulation of BBR was investigated to improve therapeutic efficacy and examined its effect on the secretion of inflammatory cytokines in cerebral ischemia in the animal model.Material and methodsNano formulation was prepared by thin-film hydration method, and characterized by particle size, zeta potential, morphology, encapsulation efficacy, and drug release in Simulated Gastric Fluid (SGF) and Simulated Intestine Fluid (SIF). Then, Wistar rats were pretreated with the drug (100 mg/kg) and nano-drug (25, 50, 75, 100 mg/kg) for 14 days. Then, on the fourteenth day, stroke induction was accomplished by Bilateral Common Carotid Artery Occlusion (BCCAO); after that, Tumor Necrosis Factor - Alpha (TNF-α), Interleukin – 1 Beta (IL-1ß), and Malondialdehyde (MDA) levels were measured in the supernatant of the whole brain, then the anti-inflammatory effect of BBR formulations was examined.Result and discussionMicelles were successfully formed with appropriate characteristics and smaller sizes than 20 nm. The Poly Dispersity Index (PDI), zeta potential, encapsulation efficacy of micelles was 0.227, − 22 mV, 81%, respectively. Also, the stability of nano micelles was higher in SGF as compared to SIF. Our outcomes of TNF-a, IL-1B, and MDA evaluation show a significant ameliorating effect of the Berberine (BBR) and BBR-loaded micelles in pretreated groups.ConclusionOur experimental data show that pretreated groups in different doses (nano BBR 100, 75, 50 mg/kg, and BBR 100 mg/kg) successfully showed decreased levels of the inflammatory factors in cerebral ischemia compared with the stroke group and pretreated group with nano BBR in the dose of 25 mg/kg. Nano BBR formulation with a lower dose can be a better candidate than conventional BBR formulation to reduce oxidative and inflammatory factors in cerebral ischemia. Therefore, BBR-loaded micelle formulation could be a promising protective agent on cerebral ischemia.

Rapid Determination of Nitrate in Brain Regions and Cerebrospinal Fluid of Transient Bilateral Common Carotid Artery Occlusion Rat Model by HPLC–UV

The present study is designed to determine the nitrate in the cortex, cerebellum, hippocampi, and cerebrospinal fluid (CSF) of Charles Foster albino rats with global ischemia. The global cerebral ischemia is performed by occluding both common carotid arteries for 1 h followed by reperfusion of 1 h. The level of nitrate is determined after 1 h of reperfusion in the brain samples and CSF by HPLC coupled with a UV detector at 212 nm. The mobile phase constitutes of 0.3 M potassium phosphate monobasic, 20% acetonitrile, and 20% methanol (pH 3.0), and 1.5 ml/min flow rate was kept for the analysis. The retention time for nitrate and nitrite was observed at 1.9 and 5.4 min, respectively. The concentration of nitrate in the cortex, hippocampi, cerebellum, and CSF was 21, 11, 23, and 06 µg/ml, respectively, in the normal rats as well as 114.97, 84.29, 92.58 and 18.07 µg/ml, respectively, in ischemic rats. The present method is simple, rapid, cost-effective and reproducible as well as suitable to analyze the nitrate level in the brain tissues and CSF in biochemical and pharmaceutical research.

Effects of resveratrol on apoptosis in a rat model of vascular dementia

Resveratrol is a natural polyphenol widely present in plants, particularly in the skin of red grapes and in wine. It possesses a wide range of biological effects and exhibits neuroprotective effects in numerous diseases. However, data evaluating the effects of resveratrol in vascular dementia (VaD) are lacking. In the present study, the permanent, bilateral common carotid artery occlusion rat model was used to study the effects of resveratrol on VaD. The Morris water maze was used to test the spatial learning and memory performance of the rats. The expression levels of Bax, Bcl-2, cleaved caspase-3 and cleaved poly(ADP-ribose) polymerase (PARP) in the hippocampus were measured. The results showed that resveratrol inhibited memory impairment in the VaD rat model, and attenuated the increases in the expression levels of Bax, cleaved caspase-3 and cleaved PARP and the reductions in the expression levels of Bcl-2 that were induced by VaD. These results provide a novel insight into the neuroprotective effects of resveratrol and its possible therapeutic role in VaD.