Ganglioside GM1 protects against high altitude cerebral edema in rats by suppressing the oxidative stress and inflammatory response via the PI3K/AKT-Nrf2 pathway.

The present study aimed to investigate the therapeutic effects of curcumin (CU) against brain edema in a rat model of hypoxia-hypercapnia (HH)-induced brain damage (HHBD). Male Sprague-Dawley rats were divided into five groups, including a control group and four treatment groups. The rats in the control group were raised under normal laboratory conditions and were injected with water, whereas the rats in the treatment groups were exposed to a low O2/high CO2 environment simulating HH conditions, and were injected with water, CU, dimethyl sulfoxide (solvent control) or monosialoganglioside GM1. After 2 weeks, the morphological characteristics of the brain tissues were analyzed using optical and electron microscopy. In addition, aquaporin (AQP)-4 protein expression levels in brain tissue samples were analyzed using streptavidin-biotin complex immunohistochemistry and western blotting, and mRNA expression levels were detected using reverse transcription-quantitative polymerase chain reaction. Severe brain edema, tissue structure disruption and increased AQP4 expression levels were detected in the brain tissues of the HH rats. Conversely, the rats treated with CU or GM1 exhibited attenuated HHBD-induced brain edema and tissue structure disruption, and decreased mRNA and protein expression levels of AQP4. The results of the present study suggested that CU treatment was able to attenuate HHBD-induced brain edema by downregulating the expression levels of AQP4 in a rat model. Therefore, CU may be considered a potential therapeutic drug for the treatment of patients with brain edema.

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Curcumin alleviates brain edema by lowering AQP4 expression levels in a rat model of hypoxia-hypercapnia-induced brain damage

Traumatic Brain Injury (TBI) is one of the most common causes of neurological damage in young populations It has been previously suggested that one of the mechanisms that underlie brain injury is Axonal Outgrowth Inhibition (AOI) that is caused by altered composition of the gangliosides on the axon surface In the present study, we have found a significant reduction of GM1 ganglioside levels in the cortex in a closed head traumatic brain injury model of a mouse, induced by a weight drop device In addition, axonal regeneration in the brains of the injured mice was affected as seen by the expression of the axonal marker pNF-H and the growth cones (visualized by F-actin and β-III-tubulin) NeuN immunostaining revealed mTBI-induced damage to neuronal survival Finally, as expected, spatial and visual memories (measured by the Y-maze and the Novel Object Recognition tests, respectively) were also damaged 7 and 30 days post injury A single low dose of GM1 shortly after the injury (2 mg/kg; IP) prevented all of the deficits mentioned above These results reveal additional insights into the neuroprotective characteristics of GM1 in prevention of biochemical, cellular and cognitive changes caused by trauma, and may suggest a potential intervention for mTBI

/pdf/gm1-ganglioside-prevents-axonal-regeneration-inhibition-and-6w8i2iso3j.pdf

GM1 ganglioside prevents axonal regeneration inhibition and cognitive deficits in a mouse model of traumatic brain injury

Cornel iridoid glycoside (CIG) is the active ingredient extracted from Cornus officinalis. Our previous studies showed that CIG had protective effects on several brain injury models. In the present study, we aimed to examine the effects and elucidate the mechanisms of CIG against traumatic brain injury (TBI). TBI was induced in the right cerebral cortex of male adult rats. The neurological and cognitive functions were evaluated by modified neurological severity score (mNSS) and object recognition test (ORT), respectively. The level of serum S100β was measured by an ELISA method. Nissl staining was used to estimate the neuron survival in the brain. The expression of proteins was determined by western blot and/or immunohistochemical staining. We found that intragastric administration of CIG in TBI rats ameliorated the neurological defects and cognitive impairment, and alleviated the neuronal loss in the injured brain. In the acute stage of TBI (24–72 h), CIG decreased the level of S100β in the serum and brain, increased the ratio of Bcl-2/Bax and decreased the expression of caspase-3 in the injured cortex. Moreover, the treatment with CIG for 30 days increased the levels of nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF), enhanced the expression of synapsin I, synaptophysin and postsynaptic density protein 95 (PSD-95), and inhibited the apoptosis-regulating factors in the chronic stage of TBI. The present study demonstrated that CIG had neuroprotective effects against TBI through inhibiting apoptosis in the acute stage and promoting neurorestoration in the chronic stage. The results suggest that CIG may be beneficial to TBI therapy.

Protective Effects of Cornel Iridoid Glycoside in Rats After Traumatic Brain Injury

GM1 ganglioside induces vasodilation and increases catalase content in the brain.

OBJECTIVE To observe the effects of ganglioside GM1 on reduction of brain edema and amelioration of cerebral metabolism after traumatic brain injury (TBI). METHODS An acute experimental closed TBI model in rats was induced by a fluid-percussion brain injury model. At five and sixty minutes after TBI, the animals were intraperitoneally injected by ganglioside GM1 (30 mg/kg) or the same volume of saline. At the 6th hour after TBI, effects of ganglioside GM1 or saline on changes of mean arterial pressure (MAP), contents of water, lactic acid (LA) and lipid peroxidation (LPO) in the injured cerebral tissues were observed. RESULTS After TBI, MAP decreased and contents of water, LA and LPO increased in brain injury group; however, MAP was back to normal levels and contents of water, LA and LPO decreased in ganglioside GM1 treated group, compared with those in brain injury group (P 0.05) was observed. CONCLUSIONS Ganglioside GM1 does have obvious neuroprotective effect on early TBI.

Xue-hua Ding

Papers

Effects of ganglioside GM1 on reduction of brain edema and amelioration of cerebral metabolism after traumatic brain injury.