Ginseng extract attenuates early MRI changes after status epilepticus and decreases subsequent reduction of hippocampal volume in the rat brain

Prolonged epileptic seizures during status epilepticus (SE) are known to cause neuronal death and lead to brain damage. Lesions in various brain regions can result in memory and cognitive impairment, thus searching of new neuroprotective drugs is important. We evaluated effects of single and chronic administration of ginseng extract on early and late changes in MRI measurements in the rat brain after lithium-pilocarpine SE. Butanol extract of ginseng root cell culture DAN-25 was administered after termination of SE. MRI study of the rat brain was performed 2, 7, and 30 days after SE. High-resolution T2-weighed images and T2-maps were obtained, and total damaged area, hippocampal volume, and T2 relaxation time in several brain structures were calculated. Single administration of ginseng extract attenuated early changes in brain structures found on day 2 after SE. Both single and chronic treatment with ginseng extract decreased brain damage on day 7 after SE. An increase in T2-relaxation time in the hippocampus on day 2 after SE was less prominent in ginseng-treated rats than in saline-treated rats. 30 days after SE, the reduction of hippocampal volume was found both in saline-treated and ginseng-treated rats; however, it was less pronounced in ginseng-treated rats. We conclude that administration of ginseng extract after SE termination reduced brain damage caused by prolonged seizures. Ginseng extract was effective during early period after SE and had a specific protective effect on the hippocampus.

[1]  Astrid Nehlig,et al.  Pathogenesis and Pharmacology of Epilepsy in the Lithium‐pilocarpine Model , 2007, Epilepsia.

[2]  R. K. Siegel Ginseng abuse syndrome. Problems with the panacea. , 1979, JAMA.

[3]  J. L. Stringer,et al.  Protective effects of ginseng components in a rodent model of neurodegeneration , 2005, Annals of neurology.

[4]  J. Jeong,et al.  Protection against kainate neurotoxicity by ginsenosides: Attenuation of convulsive behavior, mitochondrial dysfunction, and oxidative stress , 2009, Journal of neuroscience research.

[5]  G. Kissling,et al.  Two-year toxicity and carcinogenicity studies of Panax ginseng in Fischer 344 rats and B6C3F1 mice. , 2011, The American journal of Chinese medicine.

[6]  D. Fujikawa,et al.  Status Epilepticus–Induced Neuronal Loss in Humans Without Systemic Complications or Epilepsy , 2000, Epilepsia.

[7]  R. Racine,et al.  Modification of seizure activity by electrical stimulation. II. Motor seizure. , 1972, Electroencephalography and clinical neurophysiology.

[8]  P R Allegrini,et al.  Application of magnetic resonance imaging to the measurement of neurodegeneration in rat brain: MRI data correlate strongly with histology and enzymatic analysis. , 1992, Magnetic resonance imaging.

[9]  Rod C Scott,et al.  Magnetic resonance imaging findings within 5 days of status epilepticus in childhood. , 2002, Brain : a journal of neurology.

[10]  W. Löscher,et al.  Treatment with valproate after status epilepticus: Effect on neuronal damage, epileptogenesis, and behavioral alterations in rats , 2006, Neuropharmacology.

[11]  Asla Pitkänen,et al.  Progression of Brain Damage after Status Epilepticus and Its Association with Epileptogenesis: A Quantitative MRI Study in a Rat Model of Temporal Lobe Epilepsy , 2004, Epilepsia.

[12]  Katsuhiro Yamashita,et al.  Changes of relaxation times (T1, T2) and apparent diffusion coefficient after permanent middle cerebral artery occlusion in the rat: temporal evolution, regional extent, and comparison with histology , 1995, Magnetic resonance in medicine.

[13]  M. Weiner,et al.  MR spectroscopic imaging and diffusion‐weighted MRI for early detection of kainate‐induced status epilepticus in the rat , 1996, Magnetic resonance in medicine.

[14]  M. R. Nicholls,et al.  The effect of ginseng on lifespan and stress responses in mice. , 1979, Gerontology.

[15]  Jing Zhang,et al.  Ginsenoside Rb1 selectively inhibits the activity of L-type voltage-gated calcium channels in cultured rat hippocampal neurons , 2012, Acta Pharmacologica Sinica.

[16]  G. Paxinos,et al.  The Rat Brain in Stereotaxic Coordinates , 1983 .

[17]  G. E. Cox,et al.  Effects of subchronic feeding of ginseng extract G115 in beagle dogs. , 1983, Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association.

[18]  D. Treiman,et al.  The role of benzodiazepines in the management of status epilepticus , 1990, Neurology.

[19]  J. L. Stringer,et al.  Anticonvulsant Activity of Ginseng on Seizures Induced by Chemical Convulsants , 2005, Epilepsia.

[20]  K. Takagi,et al.  Pharmacological studies of Panax ginseng root: estimation of pharmacological actions of Panax ginseng root. , 1972, Japanese journal of pharmacology.

[21]  F. Crews,et al.  Verapamil protects dopaminergic neuron damage through a novel anti-inflammatory mechanism by inhibition of microglial activation , 2011, Neuropharmacology.

[22]  Rod C. Scott,et al.  Quantitative MRI predicts status epilepticus-induced hippocampal injury in the lithium–pilocarpine rat model , 2010, Epilepsy Research.

[23]  J. Olney,et al.  Systemic cholinergic agents induce seizures and brain damage in lithium-treated rats. , 1983, Science.

[24]  C. Yuan,et al.  Ginseng pharmacology: multiple constituents and multiple actions. , 1999, Biochemical pharmacology.

[25]  R. E. Blair,et al.  Time course and mechanism of hippocampal neuronal death in an in vitro model of status epilepticus: role of NMDA receptor activation and NMDA dependent calcium entry. , 2008, European journal of pharmacology.

[26]  S. Nah,et al.  Protective effect of ginsenosides, active ingredients of Panax ginseng, on kainic acid-induced neurotoxicity in rat hippocampus , 2002, Neuroscience Letters.

[27]  C. Wasterlain,et al.  Status epilepticus: pathophysiology and management in adults , 2006, The Lancet Neurology.

[28]  P. Marzola,et al.  Magnetic resonance imaging of changes elicited by status epilepticus in the rat brain: diffusion-weighted and T2-weighted images, regional blood volume maps, and direct correlation with tissue and cell damage , 2003, NeuroImage.

[29]  I. I. Brekhman,et al.  New substances of plant origin which increase nonspecific resistance. , 1969, Annual review of pharmacology.

[30]  Xiao-yan Li,et al.  Ginsenoside Rd prevents glutamate‐induced apoptosis in rat cortical neurons , 2010, Clinical and experimental pharmacology & physiology.

[31]  P. Mcgeer,et al.  Inhibition of human astrocyte and microglia neurotoxicity by calcium channel blockers , 2012, Neuropharmacology.

[32]  D. Fujikawa,et al.  Seizure‐Induced Neuronal Necrosis: Implications for Programmed Cell Death Mechanisms , 2000, Epilepsia.

[33]  Z. Bortolotto,et al.  Review: Cholinergic mechanisms and epileptogenesis. The seizures induced by pilocarpine: A novel experimental model of intractable epilepsy , 1989, Synapse.

[34]  D. Treiman,et al.  Hippocampal Pyramidal Cell Loss in Human Status Epilepticus , 1992, Epilepsia.

[35]  T. Fujiwara,et al.  Status Epilepticus in Childhood: A Retrospective Study of Intitial Convulsive Status and Subsequent Epilepsies , 1979, Folia psychiatrica et neurologica japonica.

[36]  Qianzi Yang,et al.  Ginsenoside Rd attenuates redox imbalance and improves stroke outcome after focal cerebral ischemia in aged mice , 2011, Neuropharmacology.

[37]  Jingwei Tian,et al.  Neuroprotective effect of 20(S)-ginsenoside Rg3 on cerebral ischemia in rats , 2005, Neuroscience Letters.

[38]  Gelin Xu,et al.  Suppression of local inflammation contributes to the neuroprotective effect of ginsenoside Rb1 in rats with cerebral ischemia , 2012, Neuroscience.

[39]  Xiaomian Zhou,et al.  Neuroprotection of ginsenoside Re in cerebral ischemia–reperfusion injury in rats , 2008, Journal of Asian natural products research.

[40]  Kevin W Eliceiri,et al.  NIH Image to ImageJ: 25 years of image analysis , 2012, Nature Methods.

[41]  Asla Pitkänen,et al.  Molecular and cellular basis of epileptogenesis in symptomatic epilepsy , 2009, Epilepsy & Behavior.

[42]  H. Rhim,et al.  Ginsenosides inhibit NMDA receptor-mediated epileptic discharges in cultured hippocampal neurons , 2004, Archives of pharmacal research.

[43]  Wolfgang Löscher,et al.  Prevention or Modification of Epileptogenesis after Brain Insults: Experimental Approaches and Translational Research , 2010, Pharmacological Reviews.

[44]  A. Nehlig,et al.  Magnetic Resonance Imaging in the Study of the Lithium–Pilocarpine Model of Temporal Lobe Epilepsy in Adult Rats , 2002, Epilepsia.

[45]  S. Nah,et al.  Ginsenoside Rg3 antagonizes NMDA receptors through a glycine modulatory site in rat cultured hippocampal neurons. , 2004, Biochemical and biophysical research communications.

[46]  Hans-Jochen Heinze,et al.  Volumetric Magnetic Resonance Imaging of Functionally Relevant Structural Alterations in Chronic Epilepsy after Pilocarpine‐induced Status Epilepticus in Rats , 2005, Epilepsia.

[47]  Alejandra Sierra,et al.  Quantitative T2 mapping as a potential marker for the initial assessment of the severity of damage after traumatic brain injury in rat , 2009, Experimental Neurology.