Protection of ischemic hippocampal neurons by ginsenoside Rb1, a main ingredient of ginseng root

The neuroprotective effects of riluzole, a novel antiglutamate, has been demonstrated in a model of ischemia induced in female Mongolian gerbils by transient bilateral carotid occlusion. Riluzole was administered at a dose of 4 mg/kg, i.p., just before, 4 hr after, and for the 14 d following the transient bilateral carotid occlusion (10 min). The functional sequelae of ischemic damage were assessed using a memory test (passive avoidance) and the extent of neuronal damage by histological examination and quantitative autoradiography of muscarinic cholinergic receptors in the hippocampus. The performance of the ischemic gerbils in the memory test was about half that of control animals. This memory deficit was completely reversed in animals treated with riluzole. This protective effect of riluzole was confirmed by histological and autoradiographic studies. The neuronal degeneration of CA1 pyramidal cells in the hippocampus observed in the ischemic group was not seen in the riluzole-treated animals, which resembled the control group. This neuronal degeneration in the CA1 area was confirmed by a quantitative measurement of muscarinic receptors: The binding was decreased by a third in the lacunosum moleculare, the stratum oriens, and the stratum radiatum. By contrast in riluzole-treated gerbils, this decrease was reversed by 50%. Finally, a clear-cut correlation was found between the deficit in the memory test and the decrease in muscarinic receptor binding in the CA1 fields. These results are compatible with the idea that glutamic acid may be involved in the neuronal degeneration of the hippocampus following ischemia, and could be foreseeable.(ABSTRACT TRUNCATED AT 250 WORDS)

https://www.jneurosci.org/content/jneuro/9/11/3720.full.pdf

Riluzole, a novel antiglutamate, prevents memory loss and hippocampal neuronal damage in ischemic gerbils.

Neuroprotective actions of riluzole in rodent models of global and focal cerebral ischaemia

The present study was designed to investigate the possible neuroprotective activity of ginseng roots in 5-min ischemic gerbils using a step-down passive avoidance task and subsequent neuron and synapse counts in the hippocampal CA1 region. The following drugs were administered for 7 days before the induced ischemia: red ginseng powder (RGP), crude ginseng saponin (CGS), crude ginseng non-saponin (CGNS), and pure ginsenosides Rb1, Rg1 and Ro. Oral administration of RGP significantly prevented the ischemia-induced decrease in response latency, as determined by the passive avoidance test, and rescued a significant number of ischemic hippocampal CA1 pyramidal neurons in a dose-dependent manner. Intraperitoneal injections of CGS exhibited a similar neuroprotective effect. CGNS had a significant but less potent protective effect against impaired passive avoidance task and degeneration of hippocampal CA1 neurons. Ginsenoside Rb1 significantly prolonged the response latency of ischemic gerbils and rescued a significant number of ischemic CA1 pyramidal neurons, whereas ginisenosides Rg1 and Ro were ineffective. Postischemic treatment with RGP, CGS or ginsenoside Rb1 was ineffective. The neuroprotective activities of RGP, CGS and ginsenoside Rb1 were confirmed by electron microscopy counts of synapses in individual strata of the CA1 field of ischemic gerbils pretreated with the drugs. These findings suggest that RGP and CGS are effective in the prevention of delayed neuronal death, and that ginsenoside Rb1 is one of the neuroprotective molecules within ginseng root.

Ginseng root prevents learning disability and neuronal loss in gerbils with 5-minute forebrain ischemia

Mechanism and pathogenesis of ischemia-induced neuronal damage

The effect of the psychotropic drug minaprine on brain ischemia induced by a 5-min bilateral occlusion of the carotid arteries in the mongolian gerbil was studied. Severe impairment of memory was apparent when the passive avoidance test was carried out 2 days after the bilaterally induced ischemia. When minaprine in a dose of 50 mg/kg was given p.o. 30 min before the 5-min occlusion, there was a significant improvement in the memory impairment. The amplitude of the hippocampal theta waves decreased and Nissl's degradation was apparent in the CA1 neurons in the hippocampus from 2 days after the 5-min occlusion. Changes in the hippocampal neurons were exacerbated with time. When minaprine in a dose of 50 mg/kg was given there was no decrease in the amplitude of hippocampal theta waves, and Nissl's degradation and the destruction and disappearance of the CA1 neurons diminished considerably. All these findings indicate that minaprine warrants further study for possible clinical prescription.

M Kimura

Papers

Effect of minaprine on "delayed neuronal death" in mongolian gerbils with occluded common carotid arteries.