Bilateral Common Carotid Occlusion Surgery Research Articles

Chlorogenic Acid Protects Cell Death in the Cerebellum through Anti-Apoptotic Protein Bcl2 in Transient Global Ischemia Cases

Background: Cerebellum is one of the vital components of the brain that will be affected by ischemia-reperfusion (IR) injury. IR injury will increase free radicals, which in turn can trigger apoptosis and cell death. Therefore, this study was conducted to examine the effect of chlorogenic acid administration on apoptosis and the number of cells in the cerebellum of rats with global ischemic transients.Materials and methods: Wistar rats were divided into five groups: sham-operated (C1), IR (C2), IR + 15 mg/kgBW chlorogenic acid (T1), IR + 30 mg/kgBW chlorogenic acid (T2), and IR + 60 mg/kgBW chlorogenic acid (T3). C2, T1, T2, and T3 groups received bilateral common carotid occlusion (BCCO) surgery to induce IR injury. Thirty minutes after BCCO surgery, T1, T2, and T3 rats were administered chlorogenic acid in various doses intraperitoneally. RNA extraction and real-time polymerase chain reaction (PCR) measurements were then performed on NeuN, Bcl2, Bax, caspase 3, as well as on GAPDH as housekeeping genes.Results: There were significant differences in NeuN expressions between groups, with the highest expression shown in C1 followed by T3. Bcl2 expressions were also significantly different between groups, and rats in C1 and T3 showed to be significantly higher compared to C2, while T1 was significantly lower than C1. However, Bax and caspase 3 expressions showed no significant differences.Conclusion: Chlorogenic acid in 60 mg/kgBW dose increases NeuN expression and Bcl2 mRNA expression after transient global ischemia. These increases might correlate with the heightened level of protection against apoptosis in the cerebellum, hence showing its potential in protecting neuron cells.Keywords: transient global ischemia, chlorogenic acid, cerebellum, apoptosis

Vascular and haemodynamic response following chronic hypoperfusion in the developing and mature rat

Arterial occlusion is one of the main mechanisms leading to hypoperfusion. Vascular growth and collateral circulation can compensate for arterial occlusion and reduce the effects of hypoperfusion. Aberrations in blood flow due to arterial occlusion have been identified in childhood pathologies, yet there have been limited experimental investigations in the vascular response of the developing brain. Therefore we have investigated the chronic vascular and morphological changes following bilateral common carotid occlusion (BCCAO) in both the mature and developing brain using MRI and histology. Four adult male rats were studied in experiments where CBF was measured before and immediately after BCCAO surgery. For chronic experiments 8 adult rats and 8 newborn pups (3-day old) were subjected to BCCAO or sham surgery. Single slice coronal images were obtained 3.3 mm from bregma on a 2.35 T SMIS system using dedicated sequences to measure CBF, T1, T2 and ADC. A high-resolution SE anatomical scan was obtained with 128 128 pixels, 1 mm slice thickness, 17 slices, FOV 30 mm. MR angiography (MRA) of the neck was done with 128 128 128 pixels, FOV 25 25 30 mm and visualisation by maximal intensity projection (MIP) software. To visualise the cerebro-vascular structure papaverine hydrochloride was injected intravenously to induce maximal dilatation and India ink was subsequently injected. There were significant reductions in CBF immediately after BCCAO surgery in the cortices and hippocampi (50%) and a 20% decrease in the thalami, but no reduction in the apparent diffusion coefficient (ADC) was observed, therefore oligaemic hypoperfusion was established. However, 6 months following surgery, CBF was restored in both adults and pups. No changes were observed in the ADC, T1 or T2 values 6 months post-surgery. To investigate the underlying mechanism for the return of CBF to control values, we performed MRA of the neck. As expected, signal from the common carotid arteries was present in the sham-operated rats, but was absent in the BCCAO animals. Interestingly, signal from the vertebral arteries appeared to be enhanced and the presence of collateral formation was evident. Two observers blinded to the experiment evaluated the MRA images and reported more tortuous vertebral arteries in the BCCAO adults and more midline collaterals in the BCCAO pups indicating different extracerebral modes of adaptation dependent on the age at onset of the insult. Furthermore, the vessel diameters of various arteries which make up the circle of Willis were measured 6 months after surgery. Highly significant (p<0.001) differences were seen between sham-operated and BCCOA animals in the basilar, posterior cerebral, posterior communicating arteries and in the internal carotid and anterior cerebral arteries (p<0.01). Interestingly, no significant differences were observed between adult and neonatal age-groups for any of the vessels measured (2-way ANOVA). Our studies suggest that the developing and mature animal exhibit different patterns of arteriogenesis and that the BCCAO hypoperfusion model will be useful for investigating responses to vaso-occlusive disease. Further, non-invasive MRI measurements of cerebral haemodynamics may provide a useful indicator of the homeostatic responses to chronic hypoperfusion.