Chronic bilateral common carotid artery occlusion: a model for ocular ischemic syndrome in the rat

Cho

Korean J Physiol Pharmacol

2008

In order to reproduce chronic cerebral hypoperfusion as it occurs in human aging and Alzheimer's disease, we introduced permanent, bilateral occlusion of the common carotid arteries (BCCAO) in rats (Farkas et al, 2007). Here, we induced BCCAO in two different rat strains in order to determine whether there was a strain difference in the pathogenic response to BCCAO. Male W istar and Sprague-Dawley (SD) rats (250-270 g) were subjected to BCCAO for three weeks. Klüver-Barrera and cresyl violet staining were used to evaluate white matter and gray matter damage, respectively. W istar rats had a considerably higher mortality rate (four of 14 rats) as compared to SD rats (one of 15 rats) following BCCAO. Complete loss of pupillary light reflex occurred in all Wistar rats that survived, but loss of pupillary light reflex did not occur at all in SD rats. Moreover, BCCAO induced marked vacuolation in the optic tract of Wistar rats as compared to SD rats. In contrast, SD rats showed fewer CA1 hippocampal neurons than W istar rats following BCCAO. These results suggest that the neuropathological process induced by BCCAO takes place in a region-specific pattern that varies according to the strain of rat involved.

Section: Pupillary Light Reflexmentioning

confidence: 99%

White Matter Damage and Hippocampal Neurodegeneration Induced by Permanent Bilateral Occlusion of Common Carotid Artery in the Rat: Comparison between Wistar and Sprague-Dawley Strain

Cho

Korean J Physiol Pharmacol

2008

“…It leads to a moderate reduction of blood flow, causing subtle morphological, biochemical, and behavioral changes (Osborne et al 2004;Farkas et al 2007;Kalesnykas et al 2008). Among the numerous models of retinal ischemia, BCCAO induces functional and morphological damage in the rat retina such as electrophysiological alterations, loss of the pupillary reflex, detectable neurodegenerative changes both retinal or visual system level, as well as fundoscopic and fluorescein angiographic findings paralleling the retinopathy of carotid artery occlusive disease in humans (Spertus et al 1984;Vidal-Sanz et al 2000;Lavinsky et al 2006). We have shown earlier that local treatment with pituitary adenylate cyclase-activating polypeptide or diazoxide counteracted mitochondrial dysfunction, and resulted in amelioration of BCCAO-induced retina degeneration in rats (Atlasz et al 2007a, b).…”

Section: Introductionmentioning

confidence: 99%

Protection Against Chronic Hypoperfusion-Induced Retinal Neurodegeneration by PARP Inhibition via Activation of PI-3-kinase Akt Pathway and Suppression of JNK and p38 MAP Kinases

et al. 2009

Poly(ADP-ribose) polymerase (PARP) activation is considered as a major regulator of cell death in various pathophysiological conditions, however, no direct information is available about its role in chronic hypoperfusion-induced neuronal death. Here, we provide evidence for the protective effect of PARP inhibition on degenerative retinal damage induced by bilateral common carotid artery occlusion (BCCAO), an adequate chronic hypoperfusion murine model. We found that BCCAO in adult male Wistar rats led to severe degeneration of all retinal layers that was attenuated by a carboxaminobenzimidazol-derivative PARP inhibitor (HO3089) administered unilaterally into the vitreous body immediately following carotid occlusion and then 4 times in a 2-week-period. Normal morphological structure of the retina was preserved and the thickness of the retinal layers was increased in HO3089-treated eyes compared to the BCCAO eyes. For Western blot studies, HO3089 was administered immediately after BCCAO and retinas were removed 4 h later. According to Western blot analysis utilizing phosphorylation-specific primary antibodies, besides activating poly-ADP-ribose (PAR) synthesis, BCCAO induced phosphorylation of c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (MAPK). HO3089 inhibited PAR synthesis, and decreased the phosphorylation of these proapoptotic MAPKs. In addition, HO3089 treatment induced phosphorylation, that is activation, of the protective Akt/glycogen synthase kinase (GSK)-3beta and extracellular signal-regulated kinase (ERK1/2) signaling pathways. These data indicate that PARP activation has a major role in mediating chronic hypoperfusion-induced neuronal death, and inhibition of the enzyme prevents the pathological changes both in the morphology and the kinase signaling cascades involved. These results identify PARP inhibition as a possible molecular target in the clinical management of chronic hypoperfusion-induced neurodegenerative diseases including ocular ischemic syndrome.

“…It brings damage to the brain with different severity by causing ischemia of neural cells, such as impairment of working memory and gait performance, ocular ischemic syndrome, white matter lesions, cognitive dysfunction, and so on. [1][2][3][4][5][6] Studies indicate that cerebral hypoperfusion often comes along with stroke, Alzheimer's disease (AD), and vascular dementia (VD), [7][8][9] which threaten our lives due to the high mortality and disability rate. Therefore, early monitoring of the hypoperfusion and prophylactic treatment are important.…”

Section: Introductionmentioning

confidence: 99%

Early monitoring of cerebral hypoperfusion in rats by laser speckle imaging and functional photoacoustic microscopy

et al. 2012

Abstract. Because cerebral hypoperfusion brings damage to the brain, prevention of cerebrovascular diseases correlative to hypoperfusion by studying animal models makes great sense. Since complicated cerebrovascular adaptive changes in hypoperfusion could not be revealed only by cerebral blood flow (CBF) velocity imaging, we performed multi-parameter imaging by combining laser speckle imaging and functional photoacoustic microscopy. The changes in CBF, hemoglobin oxygen saturation (SO 2 ), and total hemoglobin concentration (HbT) in single blood vessels of ipsilateral cortex were observed during transient cerebral hypoperfusion by ligating the unilateral common carotid artery in rats. CBF, SO 2 , and HbT, respectively, decreased to 37 AE 3%, 71 AE 7.5%, and 92 AE 1.3% of baseline in 6 s immediately after occlusion, and then recovered to 77 AE 4.8%, 84 AE 8%, and 96 AE 2% of baseline in 60 s. These parameters presented the decrease with different degree and the following recovery over time after ligation, the recovery of SO 2 lagged behind those of CBF and HbT, which had the similar response. The results demonstrated that complete monitoring of both cerebral hemodynamic response and oxygen metabolic changes occurred at the earliest period of cerebral hypoperfusion was possible by using the two image modalities with high temporal and spatial resolution.