Neuronal damage and decrease of central acetylcholine level following permanent occlusion of bilateral common carotid arteries in 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: Discussionmentioning

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

“…First, in rats, bilateral common carotid artery occlusion (BCCAO), which leads to chronic cerebral hypoperfusion, has been shown to result in the loss of cholinergic neurons, as demonstrated by decreased choline acetyltransferase (ChAT) and AChE activities [12,13] , as well as reduced mRNA expression of the m3 and m5 muscarinic acetylcholine (ACh) receptors [14] . Second, decreased ACh content and corresponding impairments in learning and memory were found in rats with 4-vessel occlusion [15] .…”

Section: Cholinergic Deficiency In Vad Animal Models and Vad Patientsmentioning

confidence: 99%

Cholinergic deficiency involved in vascular dementia: possible mechanism and strategy of treatment

2009

Vascular dementia (VaD) is a progressive neurodegenerative disease with a high prevalence. Several studies have recently reported that VaD patients present cholinergic deficits in the brain and cerebrospinal fluid (CSF) that may be closely related to the pathophysiology of cognitive impairment. Moreover, cholinergic therapies have shown promising effects on cognitive improvement in VaD patients. The precise mechanisms of these cholinergic agents are currently not fully understood; however, accumulating evidence indicates that these drugs may act through the cholinergic anti-inflammatory pathway, in which the efferent vagus nerve signals suppress pro-inflammatory cytokine release and inhibit inflammation, although regulation of oxidative stress and energy metabolism, alleviation of apoptosis may also be involved. In this paper, we provide a brief overview of the cholinergic treatment strategy for VaD and its relevant mechanisms of anti-inflammation.

“…It has been known that two types of brain damages are observed in the rat with BCAO 19) . One type is the infarction, observed in …”

Section: • Acknowledgementsmentioning

confidence: 99%

“…However, BCAO induces morphological abnormalities and quantifiable cell loss in hippocampus 1,8,24) . In rat brain with BCAO, neuronal cell loss occurs mainly through necrosis, and apoptosis as well 18,19) . However, the temporal change of apoptosis has not been clarified in this model.…”

mentioning

confidence: 99%

Serial Expression of Hypoxia Inducible Factor-1α and Neuronal Apoptosis in Hippocampus of Rats with Chronic Ischemic Brain

Moon

Sur

et al. 2011

J Korean Neurosurg Soc

Objective : The purpose of this study is to investigate serial changes of hypoxia-inducible factor 1α (HIF-1α), as a key regulator of hypoxic ischemia, and apoptosis of hippocampus induced by bilateral carotid arteries occlusion (BCAO) in rats. Methods : Adult male Wistar rats were subjected to the permanent BCAO. The time points studied were 1, 2, 4, 8, and 12 weeks after occlusions, with n=6 animals subjected to BCAO, and n=2 to sham operation at each time point, and brains were fixed by intracardiac perfusion fixation with 4% neutral-buffered praraformaldehyde for brain section preparation. Immunohistochemistry (IHC), western blot and terminal uridine deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay were performed to evaluate HIF-1α expression and apoptosis. Results : In IHC and western blot, HIF-1α levels were found to reach the peak at the 2nd week in the hippocampus, while apoptotic neurons, in TU-NEL assay, were maximal at the 4th week in the hippocampus, especially in the cornu ammonis 1 (CA1) region. HIF-1α levels and apoptosis were found to fluctuate during the time course. Conclusion : This study showed that BCAO induces acute ischemic responses for about 4 weeks then chronic ischemia in the hippocampus. These in vivo data are the first to show the temporal sequence of apoptosis and HIF-1α expression.