Androgen is responsible for enhanced susceptibility of melatonin against traumatic brain injury in females.

BACKGROUND: Numerous publications have demonstrated that melatonin administration is associated with mortality reduction and improvement in neurological outcomes after traumatic brain injury (TBI). However, there are significant sex differences in several diseases associated with melatonin. We aimed to determine whether androgen was responsible for enhanced susceptibility of melatonin against TBI in females, as well as potential molecular mechanisms. METHODS: Weight-drop was used to establish a rodent model of TBI. Melatonin (10 mg/kg) and testosterone (1 mg/kg) were administered three times every day for three days after TBI using subcutaneous injection, respectively. Seven days after TBI, an open field assay was used to evaluate locomotor and exploratory activities. Neuronal amount, neuronal apoptosis, and expression of phosphorylated extracellularly regulated protein kinases 1/2 (ERK1/2), c-jun N-terminal kinase 1/2 (JNK1/2), and p38 mitogen-activated protein kinase (p38MAPK) in neurons were assessed using immunofluorescence assay seven days after TBI. The expression of caspase-3, Bax, and Bcl-2 in the frontal cortex was detected using western blot. RESULTS: Compared with female rats, melatonin administration exhibited more neuroprotective effects (including improved locomotor and exploratory activities, elevated neuronal amount, and reduced neuronal apoptosis) in male rats exposed to TBI. Moreover, testosterone significantly improved locomotor and exploratory activities, elevated neuronal amount, decreased neuronal apoptosis, downregulated phosphorylation of JNK1/2- and p38MAPK-positive neurons, but upregulated phosphorylation of ERK1/2-positive neurons in the frontal cortex, and reduced the expressions of cleaved caspase-3, Bax, but increased Bcl-2 expressions in female rats exposed to TBI. CONCLUSIONS: Androgen was responsible for the enhanced susceptibility to TBI under melatonin supplementation in females through a mechanism that may be associated with MAPK pathway regulation.

[Effect of electroacupuncture on learning-memory ability of vascular dementia rats with concomitant hypertension and hyperlipemia].

OBJECTIVE: To observe the effect of electroacupuncture (EA) of acupoint recipe for "dredging Governor-Meridian, regulating vitality and strengthening the kidney" on learning-memory ability and pathological changes of cerebral minute blood vessels and hippocampal structure in hypertension-hyperlipmia-vascular dementia (HH-VD) rats. METHODS: Forty SD rats were randomly divided into sham-operation (sham) group (n=8), EA-I group [n=8, EA of "Baihui" (GV 20), "Dazhui" (GV 14), "Pishu" (BL 20) and "Shenshu" (BL 23), 80 Hz, 1 mA, 20 min/day, 15 days], EA-II group (n=8, EA of nonpoints, 5 mm lateral to the abovementioned acupoints), medication group (n=8, intragastric perfusion of Nimotong, 0.6 mg/mL, 20 mL/kg, 15 days), model group (n=8). HH-VD model was established by feeding the rat with high fat forage and by occlusion of the left renal artery and carotid artery. The animals' learning-memory ability was detected by Y-maze test, the synaptic structure of the hippocampal CA 1 region, and the pathological change of the cerebral cortex were observed by electronic microscope and light microscope, respectively. RESULTS: After modeling, the blood pressure, serum total cholesterol and triglyceride (TG) levels, and the error number (EN), total reaction time (TRT) and standard number (SN, number of paw-electric-stroke for reaching correct reactions) of Y maze test increased significantly in comparison with sham group (P<0.05). After EA, the EN, TRT and SN of EA-I , EA-II and medication groups decreased significantly in comparison with model group (P<0.01), suggesting a striking improvement of the learning-memory ability after the treatment, and the EN, TRT and SN of EA-I group and medication group were significantly lower than those of EA-II group (P<0.05). Under electronic microscope, the number of synapses in hippocampal CA 1 area of HH-VD model rats reduced obviously, its postsynaptic density (PSD) was lighter, and the synaptic vesicles were fewer. Whereas in comparison with EA-II and medication groups, the synaptic number and density in EA-I group were more and bigger, and the width, length and color of PSD increased clearly. The synaptic number of EA-II group was relatively smaller compared with the other two treatment groups. Under light microscope, the vascular walls of the cerebral minute and small arteries of model group were obviously thickened and their lumina narrowed. While in EA-I group, these pathological changes were mild. In medication group the thickening of vascular walls of partial cerebral minute and small arteries were also seen. CONCLUSION: EA of acupoint recipe for "dredging Governor-Meridian, regulating vitality and strengthening the kidney" can improve pathological changes of the synaptic structure of hippocampal CA 1 region and the vascular walls of cerebral minute and small arteries, which may contribute to its function in improving the learning-memory ability in HH-VD rats.