Scutellaria flavonoid reduced memory dysfunction and neuronal injury caused by permanent global ischemia in rats

Abstract

The purpose of this study is to investigate the effects of flavonoid, isolated from aerial parts of Scutellaria baicalensis Georgi (SSF), on memory deficits, neuronal degeneration and abnormal energy metabolism induced by permanent global ischemia in rats. The global ischemia was produced in female Sprague–Dawley rats by permanent occlusion of the bilateral common carotid arteries. The permanent global ischemia in rats resulted in a significantly increased latency of the rat to find the hidden platform and a decreased swimming distance from the target quadrant in the Morris water maze task. The pathological changes in the neurons of ischemic rats, observed in the hippocampus and cerebral cortex, included neuron loss, neuron swelling, nuclear shrinkage or disappearance, neuronophagia and reduced density of Nissl bodies in the neuron. Moreover, the levels of lactate and ATPase activity in ischemic rats were notably increased and decreased, respectively, in the hippocampus and cerebral cortex as compared with sham-operated rats. Daily oral administration of SSF (35 mg/kg, 19–20 days) dramatically reduced the decrease in learning and memory, attenuated neuronal injury and improved abnormality of energy metabolites in rats induced by global ischemia. These findings suggest that SSF may be beneficial for the treatment of vascular dementia.

Introduction

With an increasing elderly population, various aging-related diseases such as hypertension, arteriosclerosis and different forms of dementia are also increasing. According to clinical observation, the patients who are characterized by intellectual declines often suffer from global ischemia, global ischemia–hypoxia, or cerebral hemorrhage-induced vascular disorder (Diehl and Kurz, 2002, Roman, 2002). It is reported that chronic global ischemia induces neuronal damage in selective, vulnerable regions of the brain, especially the hippocampus and cerebral cortex (Wang et al., 2000, Ni et al., 1995). Further, abnormal levels in the brain of a series of metabolites such as acetylcholinesterase, glucose, lactate, ATPase, cytochrome oxidase, NOS and free radicals resulted from the neuronal damage and these chronically impaired neuronal productions can lead to deficits in learning and memory. These neuropathological events underlie vascular dementia (Borbely, 2002, de la Torre et al., 1997, Tohgi et al., 1998, Alonso et al., 2002). The permanent occlusion of the bilateral common carotid arteries in rats is used as a chronic global ischemic model to study vascular dementia and the pharmacological effects of drug. Although the global ischemic model in rats cannot completely mimic the state of clinical patients with vascular dementia, it can partially reproduce neuronal and metabolic lesions along with learning and memory deficits (Tsuchiya et al., 1993, Zhou et al., 2001, Wang et al., 2000). Any improvements from the abnormal state of the chronic global ischemic model can help predict the possibility for a vascular dementia treatment.

SSF, the novel flavonoids isolated from aerial parts of Scutellaria baicalensis Georgi, has proven to be a promising agent for palliative treatment of dementia. In previous studies, SSF has shown improvements in brain hypoxia, memory impairment and chemical neuronal damage (Shang et al., 2001, Shang et al., 2002, Shang et al., 2005). These findings inspired us to investigate whether SSF could manifest potential developments in the global ischemic model. The effects of chronic treatment with SSF on learning deficits, neuronal injury and cerebral metabolic disruption in rats induced by permanent bilateral occlusion of common carotid arteries are reported.