Subject(s)
Amnesia, Transient Global/diagnosis , Amnesia, Transient Global/etiology , Brain Infarction/complications , Brain Infarction/diagnosis , Mesencephalon/diagnostic imaging , Thalamus/diagnostic imaging , Aged , Amnesia, Transient Global/drug therapy , Brain Infarction/drug therapy , Cerebral Arteries/diagnostic imaging , Female , Humans , Mesencephalon/blood supply , Thalamus/blood supply , Vertebral Artery/diagnostic imagingABSTRACT
Extracts of Ginkgo biloba have been used in traditional medicines for centuries, and have potential for clinical applications in cerebral ischemia/reperfusion injury. However, standardized extracts have proven protective only as pre-treatments, and the major mechanisms of action remain unclear. We explored the potential of the novel extract EGB1212, which meets the United States Pharmacopeia (USP) 31 standardization criteria for pharmaceutical use, as a post-treatment after global cerebral ischemia/reperfusion (GCI/R) injury in a rat model. The pre-treated group was administered EGB1212 for 7 d prior to common carotid artery occlusion (i.e., ischemia, for 20 min). Post-treated rats received the same but starting 2 h after ischemia and continuing for 7 d. Seven days after GCI/R, brains of each group were processed for H&E staining of hippocampal CA1 neurons. Remaining rats underwent the Morris water maze and Y-maze tests of spatial learning and memory, beginning eight days after reperfusion. To assess hippocampal autophagy, light chain (LC)-3-I/LC3-II and Akt/pAkt were determined via a Western blot of rat hippocampi harvested 12, 24, or 72 h after reperfusion. EGB1212 pre- and post-treatments both improved neuronal survival and spatial learning and memory functions. Pre-treatment effectively reduced LC3-II levels and post-treatment resulted in significantly elevated pAkt levels. We conclude that EGB1212 exerted significant neuroprotection in GCI/R in both preventative and post-treatment settings. This extract shows great potential for clinical applications.
Subject(s)
Amnesia, Transient Global/drug therapy , Amnesia, Transient Global/etiology , Autophagy/drug effects , Brain Diseases/complications , CA1 Region, Hippocampal/cytology , CA1 Region, Hippocampal/pathology , Ischemic Attack, Transient/complications , Memory Disorders/drug therapy , Memory Disorders/etiology , Neurons/pathology , Neuroprotective Agents , Phytotherapy , Plant Extracts/administration & dosage , Plant Extracts/pharmacology , Reperfusion Injury/complications , Amnesia, Transient Global/pathology , Animals , CA1 Region, Hippocampal/metabolism , Disease Models, Animal , Ginkgo biloba , Male , Maze Learning/drug effects , Microtubule-Associated Proteins/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Rats , Rats, Sprague-Dawley , Time FactorsABSTRACT
PURPOSE: Brain stroke is a leading cause of death without effective treatment. B. monniera, an Indian herbal medicine, exerts antioxidant activity and antistress activity by modulating the antioxidative defence system. We wanted to test if B. monniera could alleviate the ischemia induced brain injury and cognitive dysfunction in Wistar rats. PROCEDURE: We studied the effect of B. monniera (120mg kg(-1), 160mg kg(-1) and 240mg kg(-1) P.O.) on transient intracarotid artery (ICA) occlusion induced ischemia by testing the neurobehavioral and biochemical parameters on treated and control rats. FINDINGS: B. monniera attenuated the reduced transfer latency in ischemic rats in a step through test and showed a protective effect on ischemia induced memory impairment in the plus maze task. It also showed a marginal improvement in neurodeficit score and fore limb muscle grip strength. B. monniera reduced the infarct size in the ischemic brain. It also decreased nitrite, nitrate and lipid peroxidation and significantly improved catalase activity. CONCLUSION: These observations suggest the neuroprotective and antioxidant activity of B. monniera on ischemia induced brain injury and pave the way for future investigations.
Subject(s)
Bacopa/chemistry , Brain Ischemia/drug therapy , Neuroprotective Agents/therapeutic use , Stroke/prevention & control , Amnesia, Transient Global/drug therapy , Amnesia, Transient Global/psychology , Animals , Avoidance Learning/drug effects , Behavior, Animal/drug effects , Brain/pathology , Brain Chemistry/drug effects , Catalase/metabolism , Cerebral Infarction/pathology , Cerebral Infarction/prevention & control , Glutathione Peroxidase/metabolism , Lipid Peroxidation/drug effects , Male , Maze Learning/drug effects , Memory/drug effects , Nervous System Diseases/etiology , Nervous System Diseases/prevention & control , Nitric Oxide/metabolism , Plant Extracts/therapeutic use , Postural Balance/drug effects , Rats , Rats, Wistar , Stroke/etiology , Superoxide Dismutase/metabolismABSTRACT
Calcineurin (CN) is a highly abundant phosphatase in the brain and it is the only Ca(2+)- and calmodulin-dependent protein serine/threonine phosphatase. There is considerable evidence to suggest that CN plays an essential role in activity-dependent modulation of synaptic efficacy. It has been shown recently that inhibitors of CN, such as CsA or FK506, impair memory formation in day-old chicks. In our present study, extract of Fructus cannabis (EFC) with activation of CN, extracted from Chinese traditional medicine, was used to determine the effects on memory and immunity. In the step-down-type passive avoidance test, the plant extract (0.2 g/kg) significantly improved amnesia induced by chemical drugs in mice, and greatly enhanced the ability of cell-mediated type hypersensitivity and nonspecific immune responses in normal mice. The present study provided pharmacological evidence for Chinese herbal medicine screening from molecular model.