BACKGROUND: Glutamate and oxidative stress play important roles after subarachnoid hemorrhage (SAH). The ability to modulate glutamate transporter 1 (GLT-1) and the antioxidative effect of rosiglitazone have been demonstrated. We investigated the neuroprotective effect of rosiglitazone after SAH. METHODS: SAH was induced by double blood injection. The rats were randomly divided into sham, SAH + vehicle, and SAH + rosiglitazone groups and treated with dimethyl sulfoxide, dimethyl sulfoxide, and 6 mg/kg of rosiglitazone, respectively, at 2 and 12 h after SAH induction and then daily for 6 days. Cerebrospinal fluid dialysates were collected 30 min before SAH induction and then daily for 7 days for glutamate measurement. Mortality, body weight, and neurological scores were also measured daily. On day 7 after SAH, the wall thickness and the perimeter of the basilar artery (BA), neuron variability, GLT-1 levels, glial fibrillary acidic protein (GFAP) expression and activity, and malondialdehyde, superoxide dismutase, and catalase activities were also evaluated. RESULTS: Rosiglitazone improved survival (relative risk = 0.325) and neurological functions and reduced neuronal degeneration (5.7 ± 0.8 vs. 10.0 ± 0.9; P < 0.001) compared with the SAH + vehicle group. Rosiglitazone also lowered glutamate levels by 43.5-fold and upregulated GLT-1 expression by 1.5-fold and astrocyte activity by 1.8-fold compared with the SAH + vehicle group. The increase in BA wall thickness was significantly attenuated by rosiglitazone, whereas the perimeter of the BA was increased. In addition, rosiglitazone abated the 1.9-fold increase in malondialdehyde levels and the 1.6-fold increase in catalase activity after SAH. CONCLUSION: Rosiglitazone reduced SAH mortality, neurological deficits, body weight loss, GFAP loss, and cerebral vasospasm by preventing the neurotoxicity induced by glutamate and oxidative stress.
BACKGROUND:Glutamate and oxidative stress play important roles after subarachnoid hemorrhage (SAH). The ability to modulate glutamate transporter 1 (GLT-1) and the antioxidative effect of rosiglitazone have been demonstrated. We investigated the neuroprotective effect of rosiglitazone after SAH. METHODS:SAH was induced by double blood injection. The rats were randomly divided into sham, SAH + vehicle, and SAH + rosiglitazone groups and treated with dimethyl sulfoxide, dimethyl sulfoxide, and 6 mg/kg of rosiglitazone, respectively, at 2 and 12 h after SAH induction and then daily for 6 days. Cerebrospinal fluid dialysates were collected 30 min before SAH induction and then daily for 7 days for glutamate measurement. Mortality, body weight, and neurological scores were also measured daily. On day 7 after SAH, the wall thickness and the perimeter of the basilar artery (BA), neuron variability, GLT-1 levels, glial fibrillary acidic protein (GFAP) expression and activity, and malondialdehyde, superoxide dismutase, and catalase activities were also evaluated. RESULTS:Rosiglitazone improved survival (relative risk = 0.325) and neurological functions and reduced neuronal degeneration (5.7 ± 0.8 vs. 10.0 ± 0.9; P < 0.001) compared with the SAH + vehicle group. Rosiglitazone also lowered glutamate levels by 43.5-fold and upregulated GLT-1 expression by 1.5-fold and astrocyte activity by 1.8-fold compared with the SAH + vehicle group. The increase in BA wall thickness was significantly attenuated by rosiglitazone, whereas the perimeter of the BA was increased. In addition, rosiglitazone abated the 1.9-fold increase in malondialdehyde levels and the 1.6-fold increase in catalase activity after SAH. CONCLUSION:Rosiglitazone reduced SAH mortality, neurological deficits, body weight loss, GFAP loss, and cerebral vasospasm by preventing the neurotoxicity induced by glutamate and oxidative stress.
Authors: Borja García-Bueno; Javier R Caso; Beatriz G Pérez-Nievas; Pedro Lorenzo; Juan C Leza Journal: Neuropsychopharmacology Date: 2006-11-22 Impact factor: 7.853
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Authors: Christian Burrell; Nicole E Avalon; Jason Siegel; Michael Pizzi; Tumpa Dutta; M Cristine Charlesworth; William D Freeman Journal: Expert Rev Neurother Date: 2016-07-11 Impact factor: 4.618